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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02253420
Other study ID # 16270
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date October 8, 2014
Est. completion date August 13, 2019

Study information

Verified date December 2020
Source Bayer
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 51
Est. completion date August 13, 2019
Est. primary completion date March 12, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Male or female patients = 18 years of age with histological or cytological confirmed advanced solid tumors or non-Hodgkin's lymphoma that have progressed on, or failed to respond to, therapies known to provide clinical benefit may be enrolled after signing informed consent. - Normal left ventricular ejection fraction; adequate liver, renal and bone-marrow functions as assessed by laboratory values. - Adequate performance status and life expectancy of at least 3 months. Exclusion Criteria: - Solid-tumor patients with central nervous system (CNS) metastases if treatment completed < 3 months before enrollment or lesions unstable or progressing on MRI scans performed within 1 month of enrollment or unstable symptoms of the CNS metastases. - Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF greater than NYHA Class II - Active coronary artery disease or myocardial infarction within the 6 months before study entry; any new-onset angina within the 3 months before study entry or unstable angina; cardiac arrhythmia requiring anti-arrhythmic therapy. - Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as fasting blood or plasma glucose above 125 mg/dL under 2 separate days, corresponding to 6.94 mmol/L) or HbA1c = 7%. - Use of systemic including inhaled corticosteroids within the 2 days before the start of study treatment (however, topical steroids are permitted). - Known presence of human immunodeficiency virus (HIV) infection or active hepatitis (B or C). - Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical management). - Anticancer chemotherapy, hormone therapy or immunotherapy within the 4 weeks before the first study treatment or scheduled for administration (of the above) during the study - History of, or concurrent, interstitial lung disease (ILD) or severely impaired pulmonary function. - Medications with drug-drug interaction potential for itraconazole which is to be excluded before the study and during Cycle 1 such as CYP3A4 substrates with a narrow therapeutic window or which have the potential to prolong QTc - Concomitant medication contraindicated for use with rifampin (including, but not limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or tipranavir

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Copanlisib (BAY80-6946)
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
Itraconazole
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
Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning
Copanlisib (BAY80-6946)
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

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Primary 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.
Primary 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.
Primary 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)
Secondary 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.
Secondary tmax 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.
Secondary 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.
Secondary 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.
Secondary 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
Secondary 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
Secondary PR intervals Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Secondary QRS intervals Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Secondary ECG waveform morphology Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
Secondary 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
Secondary 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)
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