Trial Outcomes & Findings for Study of Copanlisib in Hepatic or Renal Impairment (NCT NCT03172884)
NCT ID: NCT03172884
Last Updated: 2021-04-28
Results Overview
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion
Results posted on
2021-04-28
Participant Flow
Study was conducted in Germany and Romania between 14 Jun 2017 (first patient's first visit) and 13 Mar 2020 (last patient's last visit).
50 participants were screened in study. 16 were screen failure and 4 withdrew from study. 30 participants were assigned to study arms.
Participant milestones
| Measure |
Moderate Hepatic Impairment Group
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
6
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
6
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Copanlisib in Hepatic or Renal Impairment
Baseline characteristics by cohort
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 Participants
Normal hepatic and renal function group
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65.5 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
47.5 years
STANDARD_DEVIATION 11.1 • n=7 Participants
|
65.8 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
60.9 years
STANDARD_DEVIATION 6.6 • n=4 Participants
|
60.7 years
STANDARD_DEVIATION 11.7 • n=21 Participants
|
|
Age, Customized
In utero
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Preterm newborn infants (gestational age < 37 wks)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Newborns (0-27 days)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Infants and toddlers (28 days-23 months)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Children (2-11 years)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Customized
Adults (18-64 years)
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Age, Customized
From 65-84 years
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Age, Customized
85 years and over
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
BMI
|
27.90 kg/m^2
STANDARD_DEVIATION 4.68 • n=5 Participants
|
27.12 kg/m^2
STANDARD_DEVIATION 4.76 • n=7 Participants
|
26.60 kg/m^2
STANDARD_DEVIATION 3.07 • n=5 Participants
|
26.48 kg/m^2
STANDARD_DEVIATION 1.64 • n=4 Participants
|
27.02 kg/m^2
STANDARD_DEVIATION 3.53 • n=21 Participants
|
PRIMARY outcome
Timeframe: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusionCmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.
|
68.12 μg/L
Geometric Coefficient of Variation 65.50 • Interval 65.5 to
|
71.09 μg/L
Geometric Coefficient of Variation 53.90 • Interval 53.9 to
|
31.77 μg/L
Geometric Coefficient of Variation 38.25 • Interval 38.25 to
|
49.20 μg/L
Geometric Coefficient of Variation 27.24 • Interval 27.24 to
|
PRIMARY outcome
Timeframe: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusionPopulation: Participants in PK population with available data are reported.
AUC refers to area under the concentration vs time curve from 0 to infinity which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=7 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=6 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma.
|
594.9 μg*h/L
Geometric Coefficient of Variation 53.85
|
940.7 μg*h/L
Geometric Coefficient of Variation 23.70
|
373.7 μg*h/L
Geometric Coefficient of Variation 59.08
|
347.8 μg*h/L
Geometric Coefficient of Variation 23.99
|
PRIMARY outcome
Timeframe: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusionAUC(0-168) refers to AUC from time 0 to 168 hr which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h.
|
551.4 μg*h/L
Geometric Coefficient of Variation 53.78
|
853.0 μg*h/L
Geometric Coefficient of Variation 26.39
|
350.5 μg*h/L
Geometric Coefficient of Variation 48.55
|
311.9 μg*h/L
Geometric Coefficient of Variation 23.55
|
SECONDARY outcome
Timeframe: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusionPopulation: Participants in PK population with available data are reported.
The morpholinone derivative M-1 is a minor copanlisib metabolite in plasma. The PK of metabolite M-1 is routinely analyzed in addition to the PK of the parent compound, although M-1 is not considered to be a major metabolite. Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=4 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=7 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Metabolite M-1.
|
1.868 μg/L
Geometric Coefficient of Variation 53.16
|
1.356 μg/L
Geometric Coefficient of Variation 52.63
|
1.440 μg/L
Geometric Coefficient of Variation 50.36
|
1.543 μg/L
Geometric Coefficient of Variation 47.18
|
SECONDARY outcome
Timeframe: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusionPopulation: Participants in PK population with available data are reported.
The morpholinone derivative M-1 is a minor copanlisib metabolite in plasma. The PK of metabolite M-1 is routinely analyzed in addition to the PK of the parent compound, although M-1 is not considered to be a major metabolite. AUC from time 0 to 168h which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=4 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=7 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h.
|
82.62 μg*h/L
Geometric Coefficient of Variation 59.06 • Interval 59.06 to
|
83.00 μg*h/L
Geometric Coefficient of Variation 35.34 • Interval 35.34 to
|
67.12 μg*h/L
Geometric Coefficient of Variation 70.48 • Interval 70.48 to
|
74.68 μg*h/L
Geometric Coefficient of Variation 76.75 • Interval 76.75 to
|
SECONDARY outcome
Timeframe: Up to 30 days after end of treatment with study drugAdverse events are considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Any Adverse events (AE's)
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Any Serious adverse events (SAE's)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 30 days after end of treatment with study drugAdverse events are considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.
Outcome measures
| Measure |
Moderate Hepatic Impairment Group
n=8 Participants
Child-Pugh B (score 7-9) at the screening visit
|
Severe Hepatic Impairment Group
n=6 Participants
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 Participants
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 Participants
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.
Mild
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.
Moderate
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
Moderate Hepatic Impairment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Severe Hepatic Impairment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Severe Renal Impairment Group
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Participants
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate Hepatic Impairment Group
n=8 participants at risk
Subjects with Child-Pugh B (score 7-9) at the screening visit.
|
Severe Hepatic Impairment Group
n=6 participants at risk
Child-Pugh C (score 10-15) at the screening visit
|
Severe Renal Impairment Group
n=8 participants at risk
eGFR 15-29 mL/min/1.73 m\^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
|
Healthy Participants
n=8 participants at risk
Normal hepatic and renal function group
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/6 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
12.5%
1/8 • Number of events 1 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/6 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
12.5%
1/8 • Number of events 1 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/6 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
12.5%
1/8 • Number of events 1 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
|
Vascular disorders
Hypertension
|
0.00%
0/8 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
0.00%
0/6 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
25.0%
2/8 • Number of events 2 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
12.5%
1/8 • Number of events 1 • From first administration of study drug up to 30 days after end of treatment with study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Center will refrain from making any publications and shall not publish any press releases or other public announcements or statements about this Agreement, the Study, the Results of the Study and/or the Study Drug without Bayer's prior written consent.
- Publication restrictions are in place
Restriction type: OTHER