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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Copanlisib with and without concomitant Itraconazole (Arm A) | Experimental | 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:
|
|
| Copanlisib with and without concomitant Rifampin (Arm B) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Copanlisib (BAY80-6946) | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-168) | AUC (0-168): Area under the curve from dosing to 168 h after dosing | 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. |
| AUC | AUC: Area under the curve | 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. |
| Cmax | Cmax: Maximum concentration attained after dosing | 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. |
| QTcF | QTcF: Time-matched largest change of QT interval (Frederica's correction) | Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| AUC(0-tlast) | AUC(0-tlast): Area under the curve from dosing to last measurable concentration | 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. |
| tmax |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dallas | Texas | 75230 | United States | |||
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.
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|
| Itraconazole | Drug | 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 |
|
| Rifampin | Drug | Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning |
|
| Copanlisib (BAY80-6946) | Drug | 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 |
|
tmax: Time from dosing to attainment of Cmax |
| 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. |
| tlast | tlast: Time from dosing to last measurable concentration | 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. |
| t1/2 | t1/2: Terminal half-life | 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. |
| Urine [AE,ur(0-24)] | Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration | From 0-8 hours and >8 up to 24 hours after the start of copanlisib infusion on Days 1 and 15 of Cycle 1 |
| Number of participants with adverse events as a measure of safety and tolerability | Safety analysis will be conducted continuously until safety follow-up | At approximately 29 months |
| PR intervals | Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days) |
| QRS intervals | Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days) |
| ECG waveform morphology | Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days) |
| Left ventricular ejection fraction (LVEF) | MUGA scans | 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 |
| QTcB | QTcB: Bazett's corrected QT interval | Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days) |
| Edmonton |
| Alberta |
| T6G 1Z2 |
| Canada |
| Vancouver | British Columbia | V5Z 4E6 | Canada |
| Hamilton | Ontario | L8V 5C2 | Canada |
| Toronto | Ontario | M5G 2M9 | Canada |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000589253 | copanlisib |
| D017964 | Itraconazole |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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