<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01713036</url>
  </required_header>
  <id_info>
    <org_study_id>EMR 200066-008</org_study_id>
    <secondary_id>2012-002562-12</secondary_id>
    <nct_id>NCT01713036</nct_id>
  </id_info>
  <brief_title>Oral Bioavailability and Mass Balance Trial With Pimasertib</brief_title>
  <official_title>A Phase I, Open-Label, Single Center Trial to Investigate the Mass Balance, Metabolite Profile and Oral Bioavailability of Pimasertib in Cancer Patients With Locally Advanced or Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, open-label, single centered trial to evaluate the mass balance,&#xD;
      bioavailability and metabolism of pimasertib in cancer subjects with locally advanced or&#xD;
      metastatic solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2012</start_date>
  <completion_date type="Actual">July 31, 2014</completion_date>
  <primary_completion_date type="Actual">July 31, 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of [14C]-Pimasertib Following Intravenous (IV) Administration on Day 1</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of Pimasertib Following Oral Administration on Day 1</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of [14C]-Pimasertib Following IV Administration on Day 1</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib Following Oral Administration on Day 1</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral Bioavailability of Pimasertib After Single Oral Dose of Unlabeled Pimasertib and Intravenous (IV) Single Tracer Dose of [14C] Pimasertib</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1</time_frame>
    <description>Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) * 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mass Balance: Amount of Total Radioactivity Recovered Into the Urine and Feces From Time Zero to the Last Sampling Time Point (Ae0-t)</measure>
    <time_frame>Urine: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours post [14C]-labeled pimasertib dose on Day 8; Feces: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Recovery of total [14C]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of [14C]-pimasertib on Day 8. Cumulative recovery of total [14C]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentrations of [14C] Pimasertib</measure>
    <time_frame>Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentrations of Pimasertib Metabolites</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Metabolites Identified Overall and as Major</measure>
    <time_frame>Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8</time_frame>
    <description>Identification and profiling of the metabolites was done. The total number of metabolites and the number of metabolites identified as major were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Unlabeled Pimasertib</measure>
    <time_frame>Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Intravenous [14C] Pimasertib</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</measure>
    <time_frame>Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Elimination Rate Constant (λz) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
    <description>Apparent terminal elimination rate constant (λz) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Body Clearance of Unlabeled Pimasertib (CL/f) and Intravenous [14C] Pimasertib (CL)</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
    <description>The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Volume of Distribution of the Central or Plasma Compartment (Vc) of Intravenous [14C] Pimasertib</measure>
    <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] pimasertib dose on Day 1</time_frame>
    <description>The volume of distribution of the central or plasma compartment (Vc) was calculated using the formula=Dose/C0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution During the Terminal Phase Following Oral Administration (Vz/f) and the Apparent Volume of Distribution During the Terminal Phase Following Intravenous Administration (Vz) of [14C] Pimasertib</measure>
    <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1</time_frame>
    <description>The apparent volume of distribution during the terminal phase following oral administration (Vz/f) and the apparent volume of distribution during the terminal phase following intravenous administration was calculated by using the formula=Dose/( AUC0-inf* λz).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Unit of assessment was nanogram equivalent per milliliter (ng eq/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Area under the plasma concentration time curve from time zero to the last sampling time at which the concentration is at or above the lower limit of quantification was calculated by using mixed log linear trapezoidal rule. Unit of assessment was hour*nanogram equivalent per milliliter (hr*ng eq/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Area under the concentration time curve (AUC) from time zero to infinity (AUC0-inf) was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/λz. Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Elimination Rate Constant (λz) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>λz of total [14C] radioactivity was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of Total [14C] Radioactivity</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Body Clearance of Total [14C] Radioactivity From Plasma Following Oral Administration (CL/f)</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed. Apparent body clearance of total radioactivity from plasma was calculated by dividing the dose with area under the plasma concentration time curve from zero to infinity (Dose/AUC0inf).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution of Total [14C] Radioactivity During the Terminal Phase Following Oral Administration (Vz/f)</measure>
    <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Vz/f of total radioactivity during the terminal phase was calculated by dividing the dose with the product of area under the plasma concentration time curve and apparent terminal rate constant (dose/AUC0inf*λz).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Maximum observed plasma concentration (Cmax) for the metabolites M445 and M554 was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Time to reach maximum plasma concentration (Tmax) for the metabolites M445 and M554 was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>AUC from time 0 to infinity (AUC0-inf), was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/lambda z (λz). Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Elimination Rate Constant (λz) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>The λz of M445 and M554 was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of M445 and M554</measure>
    <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction Unbound of [14C] Pimasertib</measure>
    <time_frame>1.5 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
    <description>Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration multiplied by 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood/ Plasma Concentration Ratios of Total [14C] Radioactivity</measure>
    <time_frame>1.5 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Subjects Who Experienced Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)</measure>
    <time_frame>From the screening every 2 cycles until end of the treatment, assessed up to 18 months</time_frame>
    <description>Anti tumor activity defined as CR, PR, or stable disease and PD based on the investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR =Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (&lt;)10 millimeter (mm); PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions; the appearance of &gt;=1 new lesions; SD= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size &lt;10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation</measure>
    <time_frame>Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months</time_frame>
    <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30+/-2 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Locally Advanced or Metastatic Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Pimasertib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Part A: Subjects will receive unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib will be administered as a bolus injection. On Days 3-21 (except Day 8), subjects will receive unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects will receive 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [mcgCi]) of [14C] pimasertib orally. In the evening of Day 8, subjects will receive the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B : Subjects will be administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
    <arm_group_label>Pimasertib</arm_group_label>
    <other_name>MSC19363639B</other_name>
    <other_name>AS703026</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male subject with pathologically confirmed solid tumor preferentially including, but&#xD;
             not limited to pancreatic, thyroid, colorectal, lung, and renal cancer, or melanoma&#xD;
             which is locally advanced or metastatic, and either refractory to the respective&#xD;
             standard therapy for the disease or for which no effective standard therapy is&#xD;
             available&#xD;
&#xD;
          -  Subject has measurable and evaluable disease as defined by Response Evaluation&#xD;
             Criteria In Solid Tumors version 1.1 (RECIST v.1.1)&#xD;
&#xD;
          -  Age greater than or equal to 18 years and less than or equal to 65 years&#xD;
&#xD;
          -  Body mass index greater than or equal to 19 and less than or equal to 30 kilogram per&#xD;
             meter square (kg/m^2)&#xD;
&#xD;
          -  Subject has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less&#xD;
             than or equal to 1&#xD;
&#xD;
          -  Male subjects with female partners of childbearing potential must be willing to use an&#xD;
             adequate method of contraception during and for 4 weeks after the last dose of the&#xD;
             trial medication. During this time, female partners should use a contraceptive method&#xD;
             with a failure rate of less than 1 percent&#xD;
&#xD;
          -  Subject has read and understood the informed consent form and is willing and able to&#xD;
             give written informed consent before any trial related procedures are performed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bone marrow impairment as evidenced by hemoglobin less than 10.0 gram per deciliter&#xD;
             (g/dL), neutrophil count less than 1.5 * 10^9 per liter (/L), and/or platelets less&#xD;
             than 100 * 10^9/L&#xD;
&#xD;
          -  Renal impairment as evidenced by serum creatinine greater than 1.5 * upper limit of&#xD;
             normal (ULN) and calculated creatinine clearance less than 60 milliliter per minute&#xD;
             (mL/min) (Cockcroft Gault formula)&#xD;
&#xD;
          -  Liver function and liver cell integrity abnormality as defined by total bilirubin&#xD;
             greater than 1.5 * ULN, or aspartate transaminase (AST)/alanine transaminase (ALT)&#xD;
             greater than 2.5 * ULN, for subjects with liver metastases AST/ALT greater than 5 *&#xD;
             ULN&#xD;
&#xD;
          -  Primary brain tumors or clinical evidence of active brain metastasis. Subjects with a&#xD;
             history of previously treated brain tumor are eligible provided that 1 month following&#xD;
             treatment they were stable by computed tomography (CT) scan without evidence of&#xD;
             cerebral edema, and have no requirements for anticonvulsants or high doses of&#xD;
             corticosteroids&#xD;
&#xD;
          -  History of gastrointestinal disease, malabsorption syndrome or difficulty in&#xD;
             swallowing, which in the investigator's opinion might impair the absorption of&#xD;
             pimasertib&#xD;
&#xD;
          -  Any gastric, small or large bowel surgery that may impact the absorption of pimasertib&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positivity, active hepatitis&#xD;
&#xD;
          -  Chemotherapy, radiotherapy, immunotherapy, or molecular targeted cancer therapy within&#xD;
             the past 4 weeks or within 5 half-lives of the given drug, whatever is longer, prior&#xD;
             to start of trial medication or concomitantly within this trial. This restriction does&#xD;
             not apply to steroids and bisphosphonates&#xD;
&#xD;
          -  Major surgical procedure within the last 8 weeks prior to start of trial medication&#xD;
&#xD;
          -  History of uveitis and scleritis. Retinal pathology beyond normal age-related&#xD;
             processes&#xD;
&#xD;
          -  History of glaucoma. Subjects are excluded if intraocular pressure is above 21&#xD;
             millimeter of mercury (mmHg)&#xD;
&#xD;
          -  Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of&#xD;
             RVO. Subjects are also excluded if on examination an ophthalmologist finds that their&#xD;
             optic disc is at risk for a central RVO&#xD;
&#xD;
          -  Life expectancy of less than 12 weeks&#xD;
&#xD;
          -  Clinically relevant non-malignant disease which in the investigator's opinion would&#xD;
             exclude the subject from the trial, such as significant cardiovascular, pulmonary,&#xD;
             endocrine, renal and neurological disease or psychiatric disorder&#xD;
&#xD;
          -  Treatment with strong inhibitors and/or inducers of cytochrome P450 2C19 (CYP2C19) and&#xD;
             cytochrome P450 3A4 (CYP3A4). Consumption of CYP3A4 enzyme inducing or inhibiting&#xD;
             herbal drugs, fruit juices and beverages (example, grapefruit, grapefruit juice,&#xD;
             quinine [tonic water], star fruit, St John's Wort) within 2 weeks prior to start of&#xD;
             trial medication until the end of Day 21&#xD;
&#xD;
          -  Participation in a drug trial within 30 days prior to start of trial medication.&#xD;
             Participation in a trial involving administration of [14C] labeled compound(s) within&#xD;
             last 6 months prior to start of trial medication&#xD;
&#xD;
          -  Known hypersensitivity to any of the excipients used&#xD;
&#xD;
          -  Inability to understand the protocol requirements, instructions and trial-related&#xD;
             restrictions, the nature, scope, and possible consequences of the trial&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck Serono SA, an affiliate of Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
  </location_countries>
  <results_reference>
    <citation>Scheible H, Kraetzer F, Marx A, Johne A, Wimmer E. Metabolism of the MEK1/2 Inhibitor Pimasertib Involves a Novel Conjugation with Phosphoethanolamine in Patients with Solid Tumors. Drug Metab Dispos. 2017 Feb;45(2):174-182. doi: 10.1124/dmd.116.072934. Epub 2016 Dec 1.</citation>
    <PMID>27934635</PMID>
  </results_reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <results_first_submitted>July 19, 2016</results_first_submitted>
  <results_first_submitted_qc>July 19, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 31, 2016</results_first_posted>
  <last_update_submitted>July 6, 2017</last_update_submitted>
  <last_update_submitted_qc>July 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mass balance, bioavailability, cancer, 14C</keyword>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First/last subject (informed consent): Nov 2012/Apr 2013. Clinical data cutoff: Jun 2013, Study completion date: Jul 2014 (Part B)</recruitment_details>
      <pre_assignment_details>A total of 11 male subjects with locally advanced or metastatic solid cancer were screened for this trial. Six (6) subjects were enrolled and received the trial medication. Of them, 5 subjects completed Part A and further continued in Part B and completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pimasertib</title>
          <description>Part A: Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib was administered as a bolus injection. On Days 3-21 (except Day 8), subjects received unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [mcgCi]) of [14C] pimasertib orally. In the evening of Day 8, subjects received the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B : Subjects were administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set included all subjects who received at least one administration of trial medication and had at least one subsequent safety assessment.</population>
      <group_list>
        <group group_id="B1">
          <title>Pimasertib</title>
          <description>Part A: Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection. On Days 3-21 (except Day 8), subjects received unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally. In the evening of Day 8, subjects received the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B: Subjects were administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.2" spread="8.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of [14C]-Pimasertib Following Intravenous (IV) Administration on Day 1</title>
        <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of [14C]-Pimasertib Following Intravenous (IV) Administration on Day 1</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour*picogram equivalent/milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.0" lower_limit="22.33" upper_limit="58.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of Pimasertib Following Oral Administration on Day 1</title>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of Pimasertib Following Oral Administration on Day 1</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour*nanogram/milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="937.2" lower_limit="535.9" upper_limit="1639"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of [14C]-Pimasertib Following IV Administration on Day 1</title>
        <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of [14C]-Pimasertib Following IV Administration on Day 1</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour*picogram equivalent/milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.4" lower_limit="23.28" upper_limit="60.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib Following Oral Administration on Day 1</title>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib Following Oral Administration on Day 1</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour*nanogram/milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="957.4" lower_limit="548.6" upper_limit="1671"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Oral Bioavailability of Pimasertib After Single Oral Dose of Unlabeled Pimasertib and Intravenous (IV) Single Tracer Dose of [14C] Pimasertib</title>
        <description>Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) * 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.</description>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with investigational medicinal product (IMP) intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Oral Bioavailability of Pimasertib After Single Oral Dose of Unlabeled Pimasertib and Intravenous (IV) Single Tracer Dose of [14C] Pimasertib</title>
          <description>Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) * 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with investigational medicinal product (IMP) intake for the complete Part A.</population>
          <units>percentage bioavailability</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73" lower_limit="61" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mass Balance: Amount of Total Radioactivity Recovered Into the Urine and Feces From Time Zero to the Last Sampling Time Point (Ae0-t)</title>
        <description>Recovery of total [14C]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of [14C]-pimasertib on Day 8. Cumulative recovery of total [14C]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.</description>
        <time_frame>Urine: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours post [14C]-labeled pimasertib dose on Day 8; Feces: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of mass balance, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Mass Balance: Amount of Total Radioactivity Recovered Into the Urine and Feces From Time Zero to the Last Sampling Time Point (Ae0-t)</title>
          <description>Recovery of total [14C]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of [14C]-pimasertib on Day 8. Cumulative recovery of total [14C]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>percentage of dose recovered</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Urine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.8" lower_limit="43.1" upper_limit="67.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Feces</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.7" lower_limit="17.6" upper_limit="43.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.1" lower_limit="77.8" upper_limit="98.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Plasma Concentrations of [14C] Pimasertib</title>
        <time_frame>Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Concentrations of [14C] Pimasertib</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>nanogram equivalent per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Predose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hour 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="695.2" spread="213.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hour 2.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="691.2" spread="164.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hour 4.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="379.3" spread="108.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hour 10.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.6" spread="62.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hour 24.0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.62" spread="14.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Plasma Concentrations of Pimasertib Metabolites</title>
        <description>Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A. Here 'n' is the number of subjects analysed at each time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Concentrations of Pimasertib Metabolites</title>
          <description>Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A. Here 'n' is the number of subjects analysed at each time point.</population>
          <units>Nanogram equivalent per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445 (Predose)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M445 (Hour 1.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="285.2" spread="64.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M445 (Hour 2.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="262.2" spread="42.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M445 (Hour 4.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.05" spread="14.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M445 (Hour 10.0)(n=5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.58" spread="9.454"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M445 (Hour 24.0)(n=3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554(Predose)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554(Hour 1.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.53" spread="55.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554 (Hour 2.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="167.6" spread="76.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554 (Hour 4.0)(n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="169.1" spread="45.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554 (Hour 10.0) (n=5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.8" spread="24.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554 (Hour 24.0) (n=3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.33" spread="12.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Metabolites Identified Overall and as Major</title>
        <description>Identification and profiling of the metabolites was done. The total number of metabolites and the number of metabolites identified as major were reported.</description>
        <time_frame>Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Metabolites Identified Overall and as Major</title>
          <description>Identification and profiling of the metabolites was done. The total number of metabolites and the number of metabolites identified as major were reported.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>metabolites</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Major</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of Unlabeled Pimasertib</title>
        <time_frame>Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of Unlabeled Pimasertib</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="265" lower_limit="130.3" upper_limit="539.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of Intravenous [14C] Pimasertib</title>
        <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of Intravenous [14C] Pimasertib</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>picogram equivalent per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.67" lower_limit="8.051" upper_limit="19.938"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Plasma Concentration (Tmax) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</title>
        <time_frame>Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Plasma Concentration (Tmax) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unlabeled pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75" lower_limit="0.5" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>[14C] intravenous pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0.5" upper_limit="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Elimination Rate Constant (λz) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</title>
        <description>Apparent terminal elimination rate constant (λz) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Rate Constant (λz) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib</title>
          <description>Apparent terminal elimination rate constant (λz) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>per hour</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unlabeled pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1096" lower_limit="0.06315" upper_limit="0.1902"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intravenous [14C] pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1994" lower_limit="0.162" upper_limit="0.246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Body Clearance of Unlabeled Pimasertib (CL/f) and Intravenous [14C] Pimasertib (CL)</title>
        <description>The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.</description>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Body Clearance of Unlabeled Pimasertib (CL/f) and Intravenous [14C] Pimasertib (CL)</title>
          <description>The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>liter per hour</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unlabeled pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.67" lower_limit="35.91" upper_limit="109.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intravenous [14C] pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.73" lower_limit="28.57" upper_limit="73.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Volume of Distribution of the Central or Plasma Compartment (Vc) of Intravenous [14C] Pimasertib</title>
        <description>The volume of distribution of the central or plasma compartment (Vc) was calculated using the formula=Dose/C0</description>
        <time_frame>Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>The Volume of Distribution of the Central or Plasma Compartment (Vc) of Intravenous [14C] Pimasertib</title>
          <description>The volume of distribution of the central or plasma compartment (Vc) was calculated using the formula=Dose/C0</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>Liter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.668" lower_limit="50.4" upper_limit="138.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution During the Terminal Phase Following Oral Administration (Vz/f) and the Apparent Volume of Distribution During the Terminal Phase Following Intravenous Administration (Vz) of [14C] Pimasertib</title>
        <description>The apparent volume of distribution during the terminal phase following oral administration (Vz/f) and the apparent volume of distribution during the terminal phase following intravenous administration was calculated by using the formula=Dose/( AUC0-inf* λz).</description>
        <time_frame>Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution During the Terminal Phase Following Oral Administration (Vz/f) and the Apparent Volume of Distribution During the Terminal Phase Following Intravenous Administration (Vz) of [14C] Pimasertib</title>
          <description>The apparent volume of distribution during the terminal phase following oral administration (Vz/f) and the apparent volume of distribution during the terminal phase following intravenous administration was calculated by using the formula=Dose/( AUC0-inf* λz).</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>Liter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unlabeled pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="571.77" lower_limit="349.5" upper_limit="935.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intravenous [14C] pimasertib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="229.35" lower_limit="150.3" upper_limit="350.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity</title>
        <description>Unit of assessment was nanogram equivalent per milliliter (ng eq/mL).</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity</title>
          <description>Unit of assessment was nanogram equivalent per milliliter (ng eq/mL).</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>ng eq/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="774.1" lower_limit="577.8" upper_limit="1037"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity</title>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="0.75" upper_limit="2.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total [14C] Radioactivity</title>
        <description>Area under the plasma concentration time curve from time zero to the last sampling time at which the concentration is at or above the lower limit of quantification was calculated by using mixed log linear trapezoidal rule. Unit of assessment was hour*nanogram equivalent per milliliter (hr*ng eq/mL).</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total [14C] Radioactivity</title>
          <description>Area under the plasma concentration time curve from time zero to the last sampling time at which the concentration is at or above the lower limit of quantification was calculated by using mixed log linear trapezoidal rule. Unit of assessment was hour*nanogram equivalent per milliliter (hr*ng eq/mL).</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hr*ng eq/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5318" lower_limit="3453" upper_limit="8189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Total [14C] Radioactivity</title>
        <description>Area under the concentration time curve (AUC) from time zero to infinity (AUC0-inf) was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/λz. Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Total [14C] Radioactivity</title>
          <description>Area under the concentration time curve (AUC) from time zero to infinity (AUC0-inf) was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/λz. Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hr*ng eq/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5711" lower_limit="3725" upper_limit="8756"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Elimination Rate Constant (λz) of Total [14C] Radioactivity</title>
        <description>λz of total [14C] radioactivity was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Rate Constant (λz) of Total [14C] Radioactivity</title>
          <description>λz of total [14C] radioactivity was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>per hour</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04084" lower_limit="0.01986" upper_limit="0.08398"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of Total [14C] Radioactivity</title>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of Total [14C] Radioactivity</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.41" lower_limit="8.87" upper_limit="59.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Body Clearance of Total [14C] Radioactivity From Plasma Following Oral Administration (CL/f)</title>
        <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed. Apparent body clearance of total radioactivity from plasma was calculated by dividing the dose with area under the plasma concentration time curve from zero to infinity (Dose/AUC0inf).</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Body Clearance of Total [14C] Radioactivity From Plasma Following Oral Administration (CL/f)</title>
          <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed. Apparent body clearance of total radioactivity from plasma was calculated by dividing the dose with area under the plasma concentration time curve from zero to infinity (Dose/AUC0inf).</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>liter per hour</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.35" lower_limit="6.822" upper_limit="15.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution of Total [14C] Radioactivity During the Terminal Phase Following Oral Administration (Vz/f)</title>
        <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Vz/f of total radioactivity during the terminal phase was calculated by dividing the dose with the product of area under the plasma concentration time curve and apparent terminal rate constant (dose/AUC0inf*λz).</description>
        <time_frame>Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution of Total [14C] Radioactivity During the Terminal Phase Following Oral Administration (Vz/f)</title>
          <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Vz/f of total radioactivity during the terminal phase was calculated by dividing the dose with the product of area under the plasma concentration time curve and apparent terminal rate constant (dose/AUC0inf*λz).</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>Liter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="253.5" lower_limit="159.1" upper_limit="403.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of M445 and M554</title>
        <description>Maximum observed plasma concentration (Cmax) for the metabolites M445 and M554 was calculated.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of M445 and M554</title>
          <description>Maximum observed plasma concentration (Cmax) for the metabolites M445 and M554 was calculated.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>Nanogram equivalent per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="300.93" lower_limit="256.7" upper_limit="352.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="174.64" lower_limit="115" upper_limit="265.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Plasma Concentration (Tmax) of M445 and M554</title>
        <description>Time to reach maximum plasma concentration (Tmax) for the metabolites M445 and M554 was calculated.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Plasma Concentration (Tmax) of M445 and M554</title>
          <description>Time to reach maximum plasma concentration (Tmax) for the metabolites M445 and M554 was calculated.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M445 and M554</title>
        <description>Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M445 and M554</title>
          <description>Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hr*ng eq/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="976.39" lower_limit="808.7" upper_limit="1178.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1410.30" lower_limit="559.8" upper_limit="3552.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M445 and M554</title>
        <description>AUC from time 0 to infinity (AUC0-inf), was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/lambda z (λz). Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M445 and M554</title>
          <description>AUC from time 0 to infinity (AUC0-inf), was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/lambda z (λz). Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hr*ng eq/mL</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1134.72" lower_limit="938.8" upper_limit="1371.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3135.61" lower_limit="2155.9" upper_limit="4560.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Elimination Rate Constant (λz) of M445 and M554</title>
        <description>The λz of M445 and M554 was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Rate Constant (λz) of M445 and M554</title>
          <description>The λz of M445 and M554 was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>per hour</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2542" lower_limit="0.202" upper_limit="0.320"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07021" lower_limit="0.0438" upper_limit="0.1120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of M445 and M554</title>
        <time_frame>Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: For assessment of metabolites, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of M445 and M554</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>M445</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.653" lower_limit="2.11" upper_limit="3.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M554</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.81" lower_limit="6.48" upper_limit="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fraction Unbound of [14C] Pimasertib</title>
        <description>Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration multiplied by 100.</description>
        <time_frame>1.5 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Fraction Unbound of [14C] Pimasertib</title>
          <description>Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration multiplied by 100.</description>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>percentage of unbound drug</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.702" spread="0.6623"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood/ Plasma Concentration Ratios of Total [14C] Radioactivity</title>
        <time_frame>1.5 hour post [14C]-labeled pimasertib dose on Day 8</time_frame>
        <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part A: Subjects received 60 mg unlabeled Pimasertib capsules spiked with a dose of 2.6 MBq (70 mcgCi) of [14C] Pimasertib orally on Day 8.</description>
          </group>
        </group_list>
        <measure>
          <title>Blood/ Plasma Concentration Ratios of Total [14C] Radioactivity</title>
          <population>The Part A analysis set consists of all subjects who received the Part A medication, had absence of clinical trial protocol deviations affecting mass balance assessments, complied with trial medication with IMP intake for the complete Part A.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.687" spread="0.0786"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part B: Number of Subjects Who Experienced Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)</title>
        <description>Anti tumor activity defined as CR, PR, or stable disease and PD based on the investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR =Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (&lt;)10 millimeter (mm); PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions; the appearance of &gt;=1 new lesions; SD= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size &lt;10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones.</description>
        <time_frame>From the screening every 2 cycles until end of the treatment, assessed up to 18 months</time_frame>
        <population>Safety analysis set included all subjects who received at least one administration of trial medication and had at least one subsequent safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Part B : Subjects received 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Number of Subjects Who Experienced Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)</title>
          <description>Anti tumor activity defined as CR, PR, or stable disease and PD based on the investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR =Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (&lt;)10 millimeter (mm); PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions; the appearance of &gt;=1 new lesions; SD= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size &lt;10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones.</description>
          <population>Safety analysis set included all subjects who received at least one administration of trial medication and had at least one subsequent safety assessment.</population>
          <units>subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Confirmed Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation</title>
        <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30+/-2 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.</description>
        <time_frame>Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months</time_frame>
        <population>The safety analysis set included all subjects who received at least one administration of trial medication and have at least one subsequent safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pimasertib</title>
            <description>Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib was administered as a bolus injection. On Days 3-21 (except Day 8), subjects received unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [μCi]) of [14C] pimasertib orally. In the evening of Day 8, subjects received the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B : Subjects were administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation</title>
          <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30+/-2 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.</description>
          <population>The safety analysis set included all subjects who received at least one administration of trial medication and have at least one subsequent safety assessment.</population>
          <units>subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Pimasertib</title>
          <description>Part A: Subjects were administered with unlabeled pimasertib capsules orally at a single dose of 60 mg on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the IV tracer dose of 9 kBq [14C] pimasertib was administered as a bolus injection. On Days 3-21 (except Day 8), subjects received unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects received 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 MBq (70 μCi) of [14C] pimasertib orally. In the evening of Day 8, subjects received the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B: Subjects were administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchopneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypochromic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eyelid oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Retinal exudates</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteriuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pancreatic enzymes increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Toxic neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Acute generalised exanthematous pustulosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Merck KGaA Communication Center</name_or_title>
      <organization>Merck KGaA</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@merckgroup.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01713036
org study id: EMR 200066-008
secondary id: 2012-002562-12
nct id: NCT01713036
lead sponsor: 
has dmc: No
This is a Phase 1, open-label, single centered trial to evaluate the mass balance,
      bioavailability and metabolism of pimasertib in cancer subjects with locally advanced or
      metastatic solid tumors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of [14C]-Pimasertib Following Intravenous (IV) Administration on Day 1
time frame: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of Pimasertib Following Oral Administration on Day 1
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of [14C]-Pimasertib Following IV Administration on Day 1
time frame: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib Following Oral Administration on Day 1
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
measure: Oral Bioavailability of Pimasertib After Single Oral Dose of Unlabeled Pimasertib and Intravenous (IV) Single Tracer Dose of [14C] Pimasertib
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
description: Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) * 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.
measure: Mass Balance: Amount of Total Radioactivity Recovered Into the Urine and Feces From Time Zero to the Last Sampling Time Point (Ae0-t)
time frame: Urine: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours post [14C]-labeled pimasertib dose on Day 8; Feces: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post [14C]-labeled pimasertib dose on Day 8
description: Recovery of total [14C]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of [14C]-pimasertib on Day 8. Cumulative recovery of total [14C]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.
measure: Plasma Concentrations of [14C] Pimasertib
time frame: Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
measure: Plasma Concentrations of Pimasertib Metabolites
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.
measure: Number of Metabolites Identified Overall and as Major
time frame: Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
description: Identification and profiling of the metabolites was done. The total number of metabolites and the number of metabolites identified as major were reported.
measure: Maximum Observed Plasma Concentration (Cmax) of Unlabeled Pimasertib
time frame: Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
measure: Maximum Observed Plasma Concentration (Cmax) of Intravenous [14C] Pimasertib
time frame: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib
time frame: Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
measure: Apparent Terminal Elimination Rate Constant (λz) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
description: Apparent terminal elimination rate constant (λz) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
measure: Total Body Clearance of Unlabeled Pimasertib (CL/f) and Intravenous [14C] Pimasertib (CL)
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
description: The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.
measure: The Volume of Distribution of the Central or Plasma Compartment (Vc) of Intravenous [14C] Pimasertib
time frame: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] pimasertib dose on Day 1
description: The volume of distribution of the central or plasma compartment (Vc) was calculated using the formula=Dose/C0
measure: Apparent Volume of Distribution During the Terminal Phase Following Oral Administration (Vz/f) and the Apparent Volume of Distribution During the Terminal Phase Following Intravenous Administration (Vz) of [14C] Pimasertib
time frame: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
description: The apparent volume of distribution during the terminal phase following oral administration (Vz/f) and the apparent volume of distribution during the terminal phase following intravenous administration was calculated by using the formula=Dose/( AUC0-inf* λz).
measure: Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: Unit of assessment was nanogram equivalent per milliliter (ng eq/mL).
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: Area under the plasma concentration time curve from time zero to the last sampling time at which the concentration is at or above the lower limit of quantification was calculated by using mixed log linear trapezoidal rule. Unit of assessment was hour*nanogram equivalent per milliliter (hr*ng eq/mL).
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: Area under the concentration time curve (AUC) from time zero to infinity (AUC0-inf) was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/λz. Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.
measure: Apparent Terminal Elimination Rate Constant (λz) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: λz of total [14C] radioactivity was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
measure: Apparent Terminal Half-life (t1/2) of Total [14C] Radioactivity
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
measure: Total Body Clearance of Total [14C] Radioactivity From Plasma Following Oral Administration (CL/f)
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed. Apparent body clearance of total radioactivity from plasma was calculated by dividing the dose with area under the plasma concentration time curve from zero to infinity (Dose/AUC0inf).
measure: Apparent Volume of Distribution of Total [14C] Radioactivity During the Terminal Phase Following Oral Administration (Vz/f)
time frame: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
description: Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Vz/f of total radioactivity during the terminal phase was calculated by dividing the dose with the product of area under the plasma concentration time curve and apparent terminal rate constant (dose/AUC0inf*λz).
measure: Maximum Observed Plasma Concentration (Cmax) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: Maximum observed plasma concentration (Cmax) for the metabolites M445 and M554 was calculated.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: Time to reach maximum plasma concentration (Tmax) for the metabolites M445 and M554 was calculated.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: AUC from time 0 to infinity (AUC0-inf), was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/lambda z (λz). Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.
measure: Apparent Terminal Elimination Rate Constant (λz) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
description: The λz of M445 and M554 was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
measure: Apparent Terminal Half-life (t1/2) of M445 and M554
time frame: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
measure: Fraction Unbound of [14C] Pimasertib
time frame: 1.5 hour post [14C]-labeled pimasertib dose on Day 8
description: Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration multiplied by 100.
measure: Blood/ Plasma Concentration Ratios of Total [14C] Radioactivity
time frame: 1.5 hour post [14C]-labeled pimasertib dose on Day 8
measure: Part B: Number of Subjects Who Experienced Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)
time frame: From the screening every 2 cycles until end of the treatment, assessed up to 18 months
description: Anti tumor activity defined as CR, PR, or stable disease and PD based on the investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR =Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm); PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions; SD= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size <10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones.
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
time frame: Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months
description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30+/-2 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.
arm group label: Pimasertib
arm group type: Experimental
intervention type: Drug
intervention name: Pimasertib
description: Part A: Subjects will receive unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib will be administered as a bolus injection. On Days 3-21 (except Day 8), subjects will receive unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects will receive 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [mcgCi]) of [14C] pimasertib orally. In the evening of Day 8, subjects will receive the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B : Subjects will be administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.
arm group label: Pimasertib
other name: MSC19363639B
other name: AS703026
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck Serono SA, an affiliate of Merck KGaA, Darmstadt, Germany
facility: 
country: Hungary
citation: Scheible H, Kraetzer F, Marx A, Johne A, Wimmer E. Metabolism of the MEK1/2 Inhibitor Pimasertib Involves a Novel Conjugation with Phosphoethanolamine in Patients with Solid Tumors. Drug Metab Dispos. 2017 Feb;45(2):174-182. doi: 10.1124/dmd.116.072934. Epub 2016 Dec 1.
PMID: 27934635
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 