<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/NCT03036501</url>
  </required_header>
  <id_info>
    <org_study_id>BP39122</org_study_id>
    <secondary_id>2016-003461-26</secondary_id>
    <nct_id>NCT03036501</nct_id>
  </id_info>
  <brief_title>A Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled Risdiplam (RO7034067) in Healthy Male Participants</brief_title>
  <official_title>Open-label Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled RO7034067 in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, non-randomized study investigating the excretion balance, PK and&#xD;
      metabolism of a single oral dose of [14C]-labeled Risdiplam (RO7034067) in healthy male&#xD;
      participants. This study will assess the characterize mass balance, routes and rates of&#xD;
      elimination of [14C]-labeled Risdiplam (RO7034067), using conventional analytical methods and&#xD;
      assess the pharmacokinetics of total drug related [14C]-radioactivity, Risdiplam (RO7034067)&#xD;
      and its metabolite(s).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2017</start_date>
  <completion_date type="Actual">February 28, 2017</completion_date>
  <primary_completion_date type="Actual">February 28, 2017</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>Percentage of Dose Recovered as Total [14C]-radioactivity in Urine</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Urinary Amount of Total [14C]-Radioactivity in Urine</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Dose Recovered as Total [14C]-radioactivity in Feces</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Risdiplam</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Observed Plasma Concentration of Risdiplam (Tmax)</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve from Time 0 to Last Measurable Concentration Time Point (AUC0-last)</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Half-Life (t1/2)</measure>
    <time_frame>Day 1 to Day 36</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Laboratory, ECGs, Ophthalmological Assessments, And Vital Signs Abnormalities</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>[^14C]-Risdiplam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered with [^14C]-Risdiplam solution orally under fasted conditions on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[^14C]-Risdiplam</intervention_name>
    <description>[^14C]-Risdiplam 18 mg oral solution with approximately 0.75 megabecquerel MBq (20 microcuries [μCi]) of [14C]-labeled Risdiplam.</description>
    <arm_group_label>[^14C]-Risdiplam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male participants, 35 to 65 years of age (inclusive)&#xD;
&#xD;
          -  A body mass index between 18 to 30 kg/m^2 inclusive&#xD;
&#xD;
          -  Agreement to use two methods of contraception, during the treatment period and for at&#xD;
             least 4 months after the last dose of study drug. One of the contraceptive methods&#xD;
             must be a condom. The second contraceptive method must include one of the following:&#xD;
             diaphragm or cervical cap, intra-uterine device or system, or oral, injected or&#xD;
             implanted hormonal method of contraception.&#xD;
&#xD;
          -  No intention of donating sperm within 4 months of study drug administration&#xD;
&#xD;
          -  Able to participate and willing to give written informed consent and to comply with&#xD;
             the study requirements and restrictions&#xD;
&#xD;
          -  Fluent in the language of the Investigator and study staff and able to communicate&#xD;
             with the study staff&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any condition or disease detected during the medical interview/physical examination&#xD;
             that would render the participant unsuitable for the study, place the participant at&#xD;
             undue risk or interfere with the ability of the participant to complete the study in&#xD;
             the opinion of the Investigator&#xD;
&#xD;
          -  History of any clinically significant gastrointestinal, renal, hepatic, broncho-&#xD;
             pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological&#xD;
             or allergic disease, metabolic disorder, hypofertility, cancer or cirrhosis&#xD;
&#xD;
          -  Participants with any clinically significant eye pathology affecting best-corrected&#xD;
             visual acuity, or optic neuritis retinal abnormalities on spectral domain - optical&#xD;
             coherence tomography and 7-field fundus color photography as assessed by an&#xD;
             ophthalmologist&#xD;
&#xD;
          -  History or evidence of (neuro) muscular disorders&#xD;
&#xD;
          -  History or evidence of any medical condition potentially altering the absorption,&#xD;
             metabolism or elimination of drugs. Surgical history of the gastrointestinal tract&#xD;
             affecting gastric motility or altering the gastrointestinal tract&#xD;
&#xD;
          -  History or evidence of skin disorders, as assessed by a thorough skin examination of&#xD;
             the whole body&#xD;
&#xD;
          -  History of malignancy in the past 5 years&#xD;
&#xD;
          -  A history of clinically significant hypersensitivity (e.g., drugs, excipients) or&#xD;
             allergic reactions&#xD;
&#xD;
          -  Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk,&#xD;
             or any participant with a history of suicidal or homicidal attempts&#xD;
&#xD;
          -  Any major illness within one month before the screening examination or any febrile&#xD;
             illness within one week prior to screening and up to study drug administration&#xD;
&#xD;
          -  History or presence of clinically significant ECG abnormalities before study drug&#xD;
             administration or cardiovascular disease&#xD;
&#xD;
          -  Clinically significant abnormalities in laboratory test results&#xD;
&#xD;
          -  Positive results on tests for human immunodeficiency virus (HIV)-1 or HIV-2, hepatitis&#xD;
             C virus or hepatitis B virus&#xD;
&#xD;
          -  Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of&#xD;
             drugs of abuse&#xD;
&#xD;
          -  Confirmed systolic blood pressure (SBP) greater than 150 or less than 90 mmHg, and&#xD;
             diastolic blood pressure (DBP) greater than 95 or less than 50 mmHg&#xD;
&#xD;
          -  Confirmed (based on the average of at least 3 consecutive measurements) resting pulse&#xD;
             rate greater than 100 or less than 40 bpm&#xD;
&#xD;
          -  Participation in an investigational drug or device study within 90 days prior to&#xD;
             screening, as calculated from the day of follow-up from the previous study&#xD;
&#xD;
          -  Smokers who regularly smoke more than 10 cigarettes daily or equivalent tobacco-&#xD;
             containing products&#xD;
&#xD;
          -  Dietary restrictions that would prohibit the consumption of standardized meals&#xD;
&#xD;
          -  Use of any prohibited medications and food before study start and during the study&#xD;
&#xD;
          -  Participants under judicial supervision, guardianship or curatorship&#xD;
&#xD;
          -  Infrequent bowel movements (less than once per 24 hours on average)&#xD;
&#xD;
          -  Regular work with ionizing radiation or radioactive material&#xD;
&#xD;
          -  Participants who plan to attempt to father children within 4 months after study drug&#xD;
             administration&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pra International Group B.V</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>October 2, 2018</last_update_submitted>
  <last_update_submitted_qc>October 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Risdiplam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03036501
org study id: BP39122
secondary id: 2016-003461-26
nct id: NCT03036501
lead sponsor: 
has dmc: No
This is an open-label, non-randomized study investigating the excretion balance, PK and
      metabolism of a single oral dose of [14C]-labeled Risdiplam (RO7034067) in healthy male
      participants. This study will assess the characterize mass balance, routes and rates of
      elimination of [14C]-labeled Risdiplam (RO7034067), using conventional analytical methods and
      assess the pharmacokinetics of total drug related [14C]-radioactivity, Risdiplam (RO7034067)
      and its metabolite(s).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Dose Recovered as Total [14C]-radioactivity in Urine
time frame: Day 1 to Day 36
measure: Cumulative Urinary Amount of Total [14C]-Radioactivity in Urine
time frame: Day 1 to Day 36
measure: Percentage of Dose Recovered as Total [14C]-radioactivity in Feces
time frame: Day 1 to Day 36
measure: Maximum Observed Plasma Concentration (Cmax) of Risdiplam
time frame: Day 1 to Day 36
measure: Time to Maximum Observed Plasma Concentration of Risdiplam (Tmax)
time frame: Day 1 to Day 36
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Last Measurable Concentration Time Point (AUC0-last)
time frame: Day 1 to Day 36
measure: Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)
time frame: Day 1 to Day 36
measure: Apparent Terminal Elimination Half-Life (t1/2)
time frame: Day 1 to Day 36
measure: Percentage of Participants with Adverse Events
time frame: Up to 10 weeks
measure: Percentage of Participants with Laboratory, ECGs, Ophthalmological Assessments, And Vital Signs Abnormalities
time frame: Up to 10 weeks
arm group label: [^14C]-Risdiplam
arm group type: Experimental
description: Participants will be administered with [^14C]-Risdiplam solution orally under fasted conditions on Day 1.
intervention type: Drug
intervention name: [^14C]-Risdiplam
description: [^14C]-Risdiplam 18 mg oral solution with approximately 0.75 megabecquerel MBq (20 microcuries [μCi]) of [14C]-labeled Risdiplam.
arm group label: [^14C]-Risdiplam
criteria: 
gender: Male
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Risdiplam