Study of Copanlisib in Hepatic or Renal Impairment

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03172884
• Collaborator: (none)
• Enrollment: 30
• Locations: 2
• Arms: 4
• Actual Duration (Months): 35
• Patients Per Site: 15
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To evaluate the pharmacokinetics and safety of copanlisib in subjects with impaired hepatic or renal function in comparison to healthy subjects

Condition or Disease	Intervention/Treatment	Phase
Hepatic Insufficiency, Renal Insufficiency	Drug: Copanlisib (ALIQOPA, BAY80-6946)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Non-randomized, Phase 1 Single Dose Study to Evaluate the Pharmacokinetics and Safety of Copanlisib in Subjects With Impaired Hepatic or Renal Function in Comparison to Healthy Subjects
• Actual Study Start Date: Jun 14, 2017
• Actual Primary Completion Date: Mar 13, 2020
• Actual Study Completion Date: May 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BAY80-6946/Healthy subject Healthy subjects	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/moderate hepatically impaired patients Patients with Child-Pugh B (score 7-9) at the screening visit	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/severe renal impaired patients Patients with eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/severe hepatically impaired patients Patients with Child-Pugh C (score 10-15) at the screening visit	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Concentration (Cmax) of Copanlisib in Plasma. [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]

   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.

2. Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma. [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]

   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.

3. Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h. [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]

   AUC(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.

Secondary Outcome Measures

1. Maximum Observed Concentration (Cmax) of Metabolite M-1. [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]

   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.

2. Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h. [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]

   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.

3. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [Up to 30 days after end of treatment with study drug]

   Adverse 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.

4. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity. [Up to 30 days after end of treatment with study drug]

   Adverse 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

All subjects - Male and female subjects between 18 and 80 years of age with a body mass index above 18.0 and below 34.0 kg / m² and a body weight of above or equal 50 kg.

Healthy subjects

• Healthy subjects as determined by absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms, and clinical laboratory determinations. eGFR ≥ 90 mL/min/1.73 m² (according to Modification of Diet in Renal Disease [MDRD] formula).

Subjects with moderate or severe hepatic impairment

• Subjects with confirmed liver cirrhosis by at least one of the following Criteria: histologically by prior liver biopsy showing cirrhosis, liver imaging (computer tomography, and/or ultrasound and/or magnetic resonance imaging scans, and/or fibroscan), or laparoscopy.

• Child-Pugh Clinical Assessment Score 7 to 9 (moderate) or Score 10 to 15 (severe).

Subjects with severe renal impairment

• Subjects with severe renal impairment with an estimated glomerular filtration rate 15-29 mL/min/1.73 m² according to MDRD formula.

• Subjects with stable renal disease: no significant change in renal function as evidenced by serum creatinine value within ±25% from the last determination, obtained within at least 3 months before study entry and the absence of the need to start dialysis in the next 3 months.

Exclusion Criteria:

All subjects

• Active coronary artery disease or myocardial infarction within 6 months of study entry. Immuno-compromised subjects including known history/seropositivity of human immunodeficiency virus (HIV).

• Other concurrent severe and/or uncontrolled medical conditions (e.g. current diagnosis of type 1 or type 2 diabetes mellitus and with HbA1c >8.5%) that could cause unacceptable safety risks or compromise compliance with protocol.

• Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder cancer as well as localized prostate cancer.

• Uncontrolled hypertension despite optimal medical management (per investigator's assessment).

• Administration of strong CYP3A4 inhibitors or inducers within 2 weeks prior to dosing and during study conduct. (A list of these medications can be found in Section 16.6 of the protocol. However, this list may not be comprehensive).

Subjects with moderate or severe hepatic impairment

• Symptoms or history of encephalopathy (Grade III or worse)

• Failure of any other major organ other than the liver; severe infection, or any clinically significant illness within 4 weeks prior to study drug administration

• Renal failure with an eGFR <35 mL/min/1.73 m² Subjects with severe renal impairment

• Acute renal failure at study entry

• Nephrotic syndrome

• Failure of any other major organ other than the kidney

• Acute hepatorenal syndrome

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CRS Clinical-Research-Services Kiel GmbH	Kiel	Schleswig-Holstein	Germany	24105
2	Institutul National de Boli Infectioase Prof.Dr.Matei Bals	Bucuresti		Romania	021105

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

• Study Protocol - Nov 28, 2017
• Statistical Analysis Plan - Jul 25, 2018

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer Healthcare products.

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03172884
• Other Study ID Numbers: 18041; 2016-004561-51
• First Posted: Jun 1, 2017
• Last Update Posted: Apr 28, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Renal Impairment; Pharmacokinetics; Hepatic impairment; Envisaged indication: Treatment of cancer
• Additional relevant MeSH terms: Hepatic Insufficiency; Liver Failure; Renal Insufficiency

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	50 participants were screened in study. 16 were screen failure and 4 withdrew from study. 30 participants were assigned to study arms.

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Period Title: Overall Study
STARTED	8	6	8	8
COMPLETED	8	6	8	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants	Total
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group	Total of all reporting groups
Overall Participants	8	6	8	8	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (9.4)	47.5 (11.1)	65.8 (12.1)	60.9 (6.6)	60.7 (11.7)
Age, Customized (Count of Participants)
In utero	0 0%	0 0%	0 0%	0 0%	0 0%
Preterm newborn infants (gestational age < 37 wks)	0 0%	0 0%	0 0%	0 0%	0 0%
Newborns (0-27 days)	0 0%	0 0%	0 0%	0 0%	0 0%
Infants and toddlers (28 days-23 months)	0 0%	0 0%	0 0%	0 0%	0 0%
Children (2-11 years)	0 0%	0 0%	0 0%	0 0%	0 0%
Adolescents (12-17 years)	0 0%	0 0%	0 0%	0 0%	0 0%
Adults (18-64 years)	4 50%	6 100%	3 37.5%	6 75%	19 63.3%
From 65-84 years	4 50%	0 0%	5 62.5%	2 25%	11 36.7%
85 years and over	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 37.5%	1 16.7%	2 25%	3 37.5%	9 30%
Male	5 62.5%	5 83.3%	6 75%	5 62.5%	21 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	6 100%	8 100%	8 100%	30 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	8 100%	6 100%	8 100%	8 100%	30 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.90 (4.68)	27.12 (4.76)	26.60 (3.07)	26.48 (1.64)	27.02 (3.53)

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	6	8	8
Geometric Mean (Geometric Coefficient of Variation) [μg/L]	68.12 (65.50)	71.09 (53.90)	31.77 (38.25)	49.20 (27.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moderate Hepatic Impairment Group, Healthy Participants
	Comments	Moderate Hepatic Impairment vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS means
	Estimated Value	1.385
	Confidence Interval	(2-Sided) 90%; 0.921 to 2.081
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Severe Hepatic Impairment Group, Healthy Participants
	Comments	Severe hepatic impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS means
	Estimated Value	1.445
	Confidence Interval	(2-Sided) 90%; 0.998 to 2.093
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Severe Renal Impairment Group, Healthy Participants
	Comments	Severe renal impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS means
	Estimated Value	0.646
	Confidence Interval	(2-Sided) 90%; 0.486 to 0.858
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma.
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants in PK population with available data are reported.

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	6	7	6
Geometric Mean (Geometric Coefficient of Variation) [μg*h/L]	594.9 (53.85)	940.7 (23.70)	373.7 (59.08)	347.8 (23.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moderate Hepatic Impairment Group, Healthy Participants
	Comments	Moderate Hepatic Impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	1.711
	Confidence Interval	(2-Sided) 90%; 1.148 to 2.550
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Severe Hepatic Impairment Group, Healthy Participants
	Comments	Severe hepatic impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	2.705
	Confidence Interval	(2-Sided) 90%; 2.115 to 3.460
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Severe Renal Impairment Group, Healthy Participants
	Comments	Severe renal impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	1.075
	Confidence Interval	(2-Sided) 90%; 0.696 to 1.659
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h.
Description	AUC(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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	6	8	8
Geometric Mean (Geometric Coefficient of Variation) [μg*h/L]	551.4 (53.78)	853.0 (26.39)	350.5 (48.55)	311.9 (23.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moderate Hepatic Impairment Group, Healthy Participants
	Comments	Moderate Hepatic Impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	1.768
	Confidence Interval	(2-Sided) 90%; 1.251 to 2.498
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Severe Hepatic Impairment Group, Healthy Participants
	Comments	Severe hepatic impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	2.735
	Confidence Interval	(2-Sided) 90%; 2.163 to 3.459
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Severe Renal Impairment Group, Healthy Participants
	Comments	Severe renal impairment group vs Healthy Subjects
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	1.124
	Confidence Interval	(2-Sided) 90%; 0.815 to 1.549
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Metabolite M-1.
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants in PK population with available data are reported.

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	4	8	7
Geometric Mean (Geometric Coefficient of Variation) [μg/L]	1.868 (53.16)	1.356 (52.63)	1.440 (50.36)	1.543 (47.18)

5. Secondary Outcome

Title	Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h.
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants in PK population with available data are reported.

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	4	8	7
Geometric Mean (Geometric Coefficient of Variation) [μg*h/L]	82.62 (59.06)	83.00 (35.34)	67.12 (70.48)	74.68 (76.75)

6. Secondary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Description	Adverse 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.
Time Frame	Up to 30 days after end of treatment with study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	6	8	8
Any Adverse events (AE's)	0 0%	0 0%	2 25%	2 25%
Any Serious adverse events (SAE's)	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.
Description	Adverse 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.
Time Frame	Up to 30 days after end of treatment with study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moderate Hepatic Impairment Group	Severe Hepatic Impairment Group	Severe Renal Impairment Group	Healthy Participants
Arm/Group Description	Child-Pugh B (score 7-9) at the screening visit	Child-Pugh C (score 10-15) at the screening visit	eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Normal hepatic and renal function group
Measure Participants	8	6	8	8
Mild	0 0%	0 0%	2 25%	1 12.5%
Moderate	0 0%	0 0%	0 0%	1 12.5%

Adverse Events

Time Frame	From first administration of study drug up to 30 days after end of treatment with study medication.
Arm/Group Title	Moderate Hepatic Impairment Group		Severe Hepatic Impairment Group		Severe Renal Impairment Group		Healthy Participants
Arm/Group Description	Subjects with Child-Pugh B (score 7-9) at the screening visit.		Child-Pugh C (score 10-15) at the screening visit		eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation		Normal hepatic and renal function group
All Cause Mortality
	Moderate Hepatic Impairment Group		Severe Hepatic Impairment Group		Severe Renal Impairment Group		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Moderate Hepatic Impairment Group		Severe Hepatic Impairment Group		Severe Renal Impairment Group		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Moderate Hepatic Impairment Group		Severe Hepatic Impairment Group		Severe Renal Impairment Group		Healthy Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)		2/8 (25%)		2/8 (25%)
Cardiac disorders
Atrial fibrillation	0/8 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Diarrhoea	0/8 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Nervous system disorders
Headache	0/8 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Vascular disorders
Hypertension	0/8 (0%)	0	0/6 (0%)	0	2/8 (25%)	2	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.