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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
51
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
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
Cycle 1 Days 10 - 21: 600mg Rifampin oral, once daily in the morning
Unnamed facility
Dallas, Texas, United States
Unnamed facility
Edmonton, Alberta, Canada
Unnamed facility
Vancouver, British Columbia, Canada
Unnamed facility
Hamilton, Ontario, Canada
Unnamed facility
Toronto, Ontario, Canada
AUC (0-168)
AUC (0-168): Area under the curve from dosing to 168 h after dosing
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.
AUC
AUC: Area under the curve
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.
Cmax
Cmax: Maximum concentration attained after dosing
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.
QTcF
QTcF: Time-matched largest change of QT interval (Frederica's correction)
Time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
AUC(0-tlast)
AUC(0-tlast): Area under the curve from dosing to last measurable concentration
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.
tmax
tmax: Time from dosing to attainment of 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.
tlast
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
tlast: Time from dosing to last measurable concentration
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.
t1/2
t1/2: Terminal half-life
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.
Urine [AE,ur(0-24)]
Amount of drug excreted via urine during the collection interval 0 - 24 hours post administration
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
Number of participants with adverse events as a measure of safety and tolerability
Safety analysis will be conducted continuously until safety follow-up
Time frame: At approximately 29 months
PR intervals
Time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
QRS intervals
Time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)
ECG waveform morphology
Time frame: 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
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
QTcB
QTcB: Bazett's corrected QT interval
Time frame: Holter Monitoring performed on Cycle 1 Day -1 (baseline) and Cycle 1 Day 1 (each cycle is 28 days)