<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/NCT02253420</url>
  </required_header>
  <id_info>
    <org_study_id>16270</org_study_id>
    <nct_id>NCT02253420</nct_id>
  </id_info>
  <brief_title>COPANLISIB (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study in Advanced Solid Tumor and Non-Hodgkin's Lymphoma Patients</brief_title>
  <official_title>An Open-label Non-randomized, Phase 1 Study to Evaluate the Effect of (a) Itraconazole or Rifampin on the Pharmacokinetics of a Single Intravenous Dose of Copanlisib and (b) Copanlisib on Cardiovascular Safety in Subjects With Advanced Solid Tumors and Non-Hodgkin's Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effect of itraconazole or rifampin on the absorption, distribution,&#xD;
      metabolism and elimination of COPANLISIB (BAY80-6946).&#xD;
&#xD;
      To evaluate the effect of copanlisib on QT/QTc intervals and left ventricular ejection&#xD;
      fraction as parameters of cardiovascular safety.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 8, 2014</start_date>
  <completion_date type="Actual">August 13, 2019</completion_date>
  <primary_completion_date type="Actual">March 12, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC (0-168)</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>AUC (0-168): Area under the curve from dosing to 168 h after dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>AUC: Area under the curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>Cmax: Maximum concentration attained after dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>QTcF</measure>
    <time_frame>Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)</time_frame>
    <description>QTcF: Time-matched largest change of QT interval (Frederica's correction)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tlast)</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>AUC(0-tlast): Area under the curve from dosing to last measurable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>tmax: Time from dosing to attainment of Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tlast</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>tlast: Time from dosing to last measurable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.</time_frame>
    <description>t1/2: Terminal half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine [AE,ur(0-24)]</measure>
    <time_frame>From 0-8 hours and &gt;8 up to 24 hours after the start of copanlisib infusion on Days 1 and 15 of Cycle 1</time_frame>
    <description>Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>At approximately 29 months</time_frame>
    <description>Safety analysis will be conducted continuously until safety follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PR intervals</measure>
    <time_frame>Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QRS intervals</measure>
    <time_frame>Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECG waveform morphology</measure>
    <time_frame>Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction (LVEF)</measure>
    <time_frame>At baseline, in the last week of Cycle 1, and in the last 2 weeks of Cycle 2, Cycle 3, Cycle 6 and every third cycle (Cycle 9, Cycle 12, etc.) and end of treatment</time_frame>
    <description>MUGA scans</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QTcB</measure>
    <time_frame>Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)</time_frame>
    <description>QTcB: Bazett's corrected QT interval</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Medical Oncology</condition>
  <arm_group>
    <arm_group_label>Copanlisib with and without concomitant Itraconazole (Arm A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To evaluate the effect of Itraconazole on the pharmacokinetics of Copanlisib (BAY80-6946) and safety in patients with advanced solid tumor. Cycle 1 of the study will be conducted in 2 parts: Part 1 and part 2:&#xD;
Part 1 of Cycle 1: 6 patients will be enrolled and will receive 12 mg of copanlisib on Day 1 and Day 15. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21.&#xD;
Part 2 of Cycle 1: 20 patients will be enrolled and receive copanlisib doses of either 12 mg, 30 mg or 60 mg on Days 1 and 15 with the same dose administered on both days. Copanlisib dose for Part 2 will be based on safety and copanlisib pharmacokinetics in Part 1. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21.&#xD;
Cycle 2 and subsequent cycles: All patients will receive copanlisib doses of 60 mg on Days 1, 8 and 15.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Copanlisib with and without concomitant Rifampin (Arm B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To evaluate the effect of Rifampin on the pharmacokinetics of Copanlisib (BAY 80-6946) and safety in patients with advanced solid tumor or non-Hodgkin's lymphoma in Cycle 1. Approximately 30 subjects will receive 60mg of copanlisib on Cycle 1 Day 1 and Cycle 1 Day 15. Rifampin will be administered once a day from Cycle 1 Day 10 to Day 21. Holter monitoring will be performed on Cycle 1 Day -1 and Cycle 1 Day 1 to evaluate the effect of copanlisib on the QT/QTc assessment.&#xD;
Cycle 2 and subsequent cycles, all patients will receive copanlisib dose of 60 mg on Days 1, 8 and 15. Holter monitoring will be performed on Cycle 3 Day 1 and Cycle 6 Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Copanlisib (BAY80-6946)</intervention_name>
    <description>Part 1 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 12mg Cycle 1 Day 15: Single i.v. dose 12 mg Part 2 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 60mg (based on Part 1 data) Cycle 1 Day 15: Single i.v. dose 60mg (based on Part 1 data)&#xD;
Part 1 &amp; Part 2&#xD;
Cycle 2 and subsequent cycles:&#xD;
Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg</description>
    <arm_group_label>Copanlisib with and without concomitant Itraconazole (Arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>Cycle 1 Day 12: 2 x 200 mg itraconazole oral (two doses, 12 hours apart) Cycle 1 Days 13-21: 200 mg itraconazole oral, once daily in the morning</description>
    <arm_group_label>Copanlisib with and without concomitant Itraconazole (Arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampin</intervention_name>
    <description>Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning</description>
    <arm_group_label>Copanlisib with and without concomitant Rifampin (Arm B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Copanlisib (BAY80-6946)</intervention_name>
    <description>Cycle 1 Day 1: Single i.v. dose 60mg Cycle 1 Day 15: Single i.v. dose 60mg&#xD;
Cycle 2 and subsequent cycles:&#xD;
Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg</description>
    <arm_group_label>Copanlisib with and without concomitant Rifampin (Arm B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients ≥ 18 years of age with histological or cytological confirmed&#xD;
             advanced solid tumors or non-Hodgkin's lymphoma that have progressed on, or failed to&#xD;
             respond to, therapies known to provide clinical benefit may be enrolled after signing&#xD;
             informed consent.&#xD;
&#xD;
          -  Normal left ventricular ejection fraction; adequate liver, renal and bone-marrow&#xD;
             functions as assessed by laboratory values.&#xD;
&#xD;
          -  Adequate performance status and life expectancy of at least 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Solid-tumor patients with central nervous system (CNS) metastases if treatment&#xD;
             completed &lt; 3 months before enrollment or lesions unstable or progressing on MRI scans&#xD;
             performed within 1 month of enrollment or unstable symptoms of the CNS metastases.&#xD;
&#xD;
          -  Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a&#xD;
             history of CHF greater than NYHA Class II&#xD;
&#xD;
          -  Active coronary artery disease or myocardial infarction within the 6 months before&#xD;
             study entry; any new-onset angina within the 3 months before study entry or unstable&#xD;
             angina; cardiac arrhythmia requiring anti-arrhythmic therapy.&#xD;
&#xD;
          -  Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as fasting&#xD;
             blood or plasma glucose above 125 mg/dL under 2 separate days, corresponding to 6.94&#xD;
             mmol/L) or HbA1c ≥ 7%.&#xD;
&#xD;
          -  Use of systemic including inhaled corticosteroids within the 2 days before the start&#xD;
             of study treatment (however, topical steroids are permitted).&#xD;
&#xD;
          -  Known presence of human immunodeficiency virus (HIV) infection or active hepatitis (B&#xD;
             or C).&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic blood pressure [BP] &gt;150 mmHg or diastolic blood&#xD;
             pressure &gt; 90 mmHg despite optimal medical management).&#xD;
&#xD;
          -  Anticancer chemotherapy, hormone therapy or immunotherapy within the 4 weeks before&#xD;
             the first study treatment or scheduled for administration (of the above) during the&#xD;
             study&#xD;
&#xD;
          -  History of, or concurrent, interstitial lung disease (ILD) or severely impaired&#xD;
             pulmonary function.&#xD;
&#xD;
          -  Medications with drug-drug interaction potential for itraconazole which is to be&#xD;
             excluded before the study and during Cycle 1 such as CYP3A4 substrates with a narrow&#xD;
             therapeutic window or which have the potential to prolong QTc&#xD;
&#xD;
          -  Concomitant medication contraindicated for use with rifampin (including, but not&#xD;
             limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide,&#xD;
             triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A&#xD;
             (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and&#xD;
             simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine,&#xD;
             ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine),&#xD;
             atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or&#xD;
             tipranavir&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.bayer.com/</url>
    <description>Click here to find results for studies related to Bayer products.</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>December 11, 2020</last_update_submitted>
  <last_update_submitted_qc>December 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1</keyword>
  <keyword>Advanced solid tumor</keyword>
  <keyword>non-Hodgkin's lymphoma</keyword>
  <keyword>PI3 Kinase inhibitor</keyword>
  <keyword>Drug-drug Interaction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
    <mesh_term>Rifampin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA &quot;Principles for responsible clinical trial data sharing&quot;. This pertains to scope, timepoint and process of data access.&#xD;
As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.&#xD;
Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.</ipd_description>
  </patient_data>
  <!-- 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/NCT02253420
org study id: 16270
nct id: NCT02253420
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the effect of itraconazole or rifampin on the absorption, distribution,
      metabolism and elimination of COPANLISIB (BAY80-6946).

      To evaluate the effect of copanlisib on QT/QTc intervals and left ventricular ejection
      fraction as parameters of cardiovascular safety.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC (0-168)
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: AUC (0-168): Area under the curve from dosing to 168 h after dosing
measure: AUC
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: AUC: Area under the curve
measure: Cmax
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: Cmax: Maximum concentration attained after dosing
measure: QTcF
time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
description: QTcF: Time-matched largest change of QT interval (Frederica's correction)
measure: AUC(0-tlast)
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: AUC(0-tlast): Area under the curve from dosing to last measurable concentration
measure: tmax
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: tmax: Time from dosing to attainment of Cmax
measure: tlast
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: tlast: Time from dosing to last measurable concentration
measure: t1/2
time frame: Within cycle 1, at pre-dose and at 10 min, 1, 1.33 (arm B)1.5 (arm A), 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120, and 168 hours after start of drug infusion on Days 1 and 15.
description: t1/2: Terminal half-life
measure: Urine [AE,ur(0-24)]
time frame: From 0-8 hours and >8 up to 24 hours after the start of copanlisib infusion on Days 1 and 15 of Cycle 1
description: Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: At approximately 29 months
description: Safety analysis will be conducted continuously until safety follow-up
measure: PR intervals
time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
measure: QRS intervals
time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
measure: ECG waveform morphology
time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
measure: Left ventricular ejection fraction (LVEF)
time frame: At baseline, in the last week of Cycle 1, and in the last 2 weeks of Cycle 2, Cycle 3, Cycle 6 and every third cycle (Cycle 9, Cycle 12, etc.) and end of treatment
description: MUGA scans
measure: QTcB
time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
description: QTcB: Bazett's corrected QT interval
arm group label: Copanlisib with and without concomitant Itraconazole (Arm A)
arm group type: Experimental
description: To evaluate the effect of Itraconazole on the pharmacokinetics of Copanlisib (BAY80-6946) and safety in patients with advanced solid tumor. Cycle 1 of the study will be conducted in 2 parts: Part 1 and part 2:
Part 1 of Cycle 1: 6 patients will be enrolled and will receive 12 mg of copanlisib on Day 1 and Day 15. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21.
Part 2 of Cycle 1: 20 patients will be enrolled and receive copanlisib doses of either 12 mg, 30 mg or 60 mg on Days 1 and 15 with the same dose administered on both days. Copanlisib dose for Part 2 will be based on safety and copanlisib pharmacokinetics in Part 1. Itraconazole 200 mg will be administered twice a day on Day 12 and then once daily from Days 13 to 21.
Cycle 2 and subsequent cycles: All patients will receive copanlisib doses of 60 mg on Days 1, 8 and 15.
arm group label: Copanlisib with and without concomitant Rifampin (Arm B)
arm group type: Experimental
description: To evaluate the effect of Rifampin on the pharmacokinetics of Copanlisib (BAY 80-6946) and safety in patients with advanced solid tumor or non-Hodgkin's lymphoma in Cycle 1. Approximately 30 subjects will receive 60mg of copanlisib on Cycle 1 Day 1 and Cycle 1 Day 15. Rifampin will be administered once a day from Cycle 1 Day 10 to Day 21. Holter monitoring will be performed on Cycle 1 Day -1 and Cycle 1 Day 1 to evaluate the effect of copanlisib on the QT/QTc assessment.
Cycle 2 and subsequent cycles, all patients will receive copanlisib dose of 60 mg on Days 1, 8 and 15. Holter monitoring will be performed on Cycle 3 Day 1 and Cycle 6 Day 1.
intervention type: Drug
intervention name: Copanlisib (BAY80-6946)
description: Part 1 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 12mg Cycle 1 Day 15: Single i.v. dose 12 mg Part 2 of Cycle 1 Cycle 1 Day 1: Single i.v. dose 60mg (based on Part 1 data) Cycle 1 Day 15: Single i.v. dose 60mg (based on Part 1 data)
Part 1 & Part 2
Cycle 2 and subsequent cycles:
Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg
arm group label: Copanlisib with and without concomitant Itraconazole (Arm A)
intervention type: Drug
intervention name: Itraconazole
description: Cycle 1 Day 12: 2 x 200 mg itraconazole oral (two doses, 12 hours apart) Cycle 1 Days 13-21: 200 mg itraconazole oral, once daily in the morning
arm group label: Copanlisib with and without concomitant Itraconazole (Arm A)
intervention type: Drug
intervention name: Rifampin
description: Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning
arm group label: Copanlisib with and without concomitant Rifampin (Arm B)
intervention type: Drug
intervention name: Copanlisib (BAY80-6946)
description: Cycle 1 Day 1: Single i.v. dose 60mg Cycle 1 Day 15: Single i.v. dose 60mg
Cycle 2 and subsequent cycles:
Day 1: Single i.v. dose of 60mg Day 8: Single i.v. dose of 60mg Day15: Single i.v. dose of 60mg
arm group label: Copanlisib with and without concomitant Rifampin (Arm B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
url: https://clinicaltrials.bayer.com/
description: Click here to find results for studies related to Bayer products.
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Itraconazole
mesh term: Rifampin
sharing ipd: Undecided
ipd description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.
As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.
Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.