Safety and Efficacy of Bexagliflozin in Subjects With Moderate Hepatic Impairment

• Sponsor: Theracos (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03557658
• Collaborator: (none)
• Enrollment: 16
• Locations: 2
• Arms: 2
• Actual Duration (Months): 5
• Patients Per Site: 8
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the drug exposure and drug effects on subjects with moderate hepatic impairment after a single oral dose of bexagliflozin tablets, 20mg. The study will also evaluate how safe the study drug is and how well the study drug is tolerated in subjects with moderate hepatic impairment.

Condition or Disease	Intervention/Treatment	Phase
Type2 Diabetes Mellitus	Drug: Bexagliflozin	Phase 1

Detailed Description

This was a Phase 1, open-label, parallel-group study designed to assess the effect of moderate hepatic impairment on the PK and PD of orally administered bexagliflozin tablets. A total of 16 subjects comprising eight with moderate hepatic impairment (Child Pugh total score 7 to 9) and eight healthy, matched controls, were enrolled and received a single oral dose of bexagliflozin tablets, 20 mg, after an overnight fast. Food was withheld for at least 2 h after dosing. Water was allowed as desired except within 1 h of drug administration.

Blood samples were collected prior to dosing, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose.

The unbound fraction of bexagliflozin at 24 h post dose and at the maximum plasma concentration for each subject was determined by equilibrium dialysis.

Urine samples for PD analysis were collected for the 12 h interval preceding dosing and for the 0 - 12 h, 12 - 24 h, 24 - 36 h, and 36 - 48 h intervals following dosing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Parallel-group Study to Evaluate the Effect of Moderate Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Bexagliflozin
• Actual Study Start Date: Jul 26, 2018
• Actual Primary Completion Date: Dec 26, 2018
• Actual Study Completion Date: Dec 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hepatic Impaired Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9)	Drug: Bexagliflozin; Single oral dose of bexagliflozin tablet, 20 mg
Experimental: Healthy Volunteer Subjects with normal hepatic function	Drug: Bexagliflozin; Single oral dose of bexagliflozin tablet, 20 mg

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Plasma Concentration) [Up to 48 hours]

   Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).

2. Tmax (Time of Maximum Observed Plasma Concentration) [Up to 48 hours]

   Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).

3. T1/2 (Apparent Terminal Elimination Half-life) [Up to 48 hours]

   Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).

4. AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) [Up to 48 hours]

   Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).

5. Urinary Glucose Excretion 0-48 Hours [0-48 hours]

   Pre-dose urine samples were collected from -12 to 0 h for baseline measurement of pharmacodynamic parameters. Post-dose urine samples were collected without preservative in four batches: 0 to 12 h, 12 to 24 h, 24 to 36h, and 36 to 48 h after dosing. Urine aliquots were prepared from well mixed collections for the assessment of pharmacodynamics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Each subject had to meet the following criteria to be eligible for the study:

1. Be male or female adults between the age of 18 and 75 years

2. Have a body mass index (BMI) of 18.0 kg/m2 to 40.0 kg/m2

3. Have adequate venous access at multiple sites in both arms

4. Be willing to be confined to the clinical research facility as required by the protocol

5. Be able to comprehend the explanation of the informed consent and be willing to provide written informed consent in accordance with institutional and regulatory guidelines

6. For subjects in the hepatic impairment group only: Be diagnosed with moderate hepatic impairment with a Child-Pugh score 7 to 9 and be in stable general health apart from hepatic impairment and its related conditions.

7. For subjects in the healthy control group only:

• Be in general good health with matching demographics and baseline characteristics to individual subjects in the hepatic impairment group by age (± 10 years), weight (± 10%), sex, and smoking status

• Exhibit neither evidence of an active infection nor undergoing any treatment with antibiotics at the time of Screening.

Prospective subjects who met any of the following criteria were ineligible to participate:

1. A clinically significant history of allergy to drugs or latex

2. A positive alcohol or drug result based on urine sample or breathalyzer testing at Screening or at clinic admission

3. A donation of 400 mL of whole blood within two months, 200 mL of whole blood within one month, or blood components or plasma within 14 days prior to Day 0

4. A history of exposure to an investigational drug within 30 days or 5 half-lives of the investigational drug prior to Day 0, whichever was longer

5. A history of exposure to any SGLT2 inhibitor within 3 months prior to Day 0 or participation in previous bexagliflozin clinical trials

6. A history of exposure to probenecid, rifampin, or any potential strong UGT1A9 inducers or inhibitors within 2 months of Day 0

7. A clinically significant abnormal electrocardiogram (ECG) that includes but is not limited to: heart rate < 40 or > 110 bpm, QRS> 160 ms, QTc> 480 ms (corrected by Bazett's formula), or any clinically significant arrhythmia including Mobitz type II 2nd Degree Heart block and bifascicular block

8. A history of human immunodeficiency virus (HIV) infection or a positive titer for HIV antibody

9. A history of vaccination (with the exception of the flu vaccine) within 30 days prior to Day 0

10. An estimated glomerular filtration rate (eGFR) < 60 mL·min-1 per 1.73 m2 as calculated by the modification of diet in renal disease study equation

11. Severe or moderate renal dysfunction or a history of kidney, other organ, bone marrow, or stem cell transplant

12. If male, unwilling to refrain from donating sperm or to use appropriate birth control when engaging in sexual intercourse for the duration of the study and a period of 14 days after discharge from the clinic. Surgically sterile male subjects were eligible

13. If female and of childbearing potential, unwilling to use an adequate method of contraception to avoid or prevent pregnancy for the duration of the study and 14 days after discharge from the clinic. Surgically sterile (as a result of hysterectomy or bilateral oophorectomy), or postmenopausal (absence of menses greater than 12 months and age > 45 years) female subjects were eligible. All females were to have had a negative pregnancy test at Screening and at clinic admission

14. Unwillingness to forgo consumption of grapefruit and grapefruit products from 7 days prior to Day 0 through discharge from the clinic

15. Pre existing thrombocytopenia (platelet blood count < 30,000 platelets) at Screening or other clinically significant findings in complete blood count (CBC) test.

16. A history of current febrile illness, hepatocellular carcinoma, acute liver disease, severe hepatic encephalopathy, or biliary liver cirrhosis.

17. A history of significant acute medical illness (new conditions and/or exacerbation of pre existing conditions or major surgery within 4 weeks of study drug administration), active alcoholic hepatitis, current or recent (within 2 months before Day 0) history of significant gastrointestinal disease

18. Clinical evidence of severe ascites, as judged by the Investigator

19. A history of surgical portosystemic shunt

20. For subjects in the healthy control group only:

• A seated systolic blood pressure (SBP) of < 90 or > 140 mmHg, confirmed by repeat measurement

• A seated diastolic blood pressure (DBP) of < 40 or > 90 mmHg

• A history of vitamin preparation or supplement use (including St. John's Wort and ginseng) within 7 days prior to Day 0, or caffeine and methylxanthine (e.g., tea, chocolate) containing foods/beverages within 48 h prior to Day 0

• A history of prescription or over-the-counter (OTC) drug use within 7 days or 5 half lives of the drug, whichever was longer, prior to Day 0

• A history of liver disease or liver injury as indicated by an alanine aminotransferase (ALT), aspartate aminotransferase (AST), > 2.5 × the upper limit of normal (ULN) at Screening, or serum bilirubin > 1.5 × ULN

• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

1. For subjects in the hepatic impairment group only:

• A seated SBP of < 80 or > 160 mmHg, confirmed by repeat measurement

• A seated DBP of < 40 or > 100 mmHg

• A history of any new prescription medication within 30 days prior to Day 0

• A history of fluctuating or rapidly deteriorating hepatic function or the production of widely varying or worsening clinical and/or laboratory signs of hepatic impairment within the screening period

1. Any other serious medical condition that, in the opinion of the Investigator, would pose a significant risk to the subject or interfere with the interpretation of safety, PK, or PD data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Site 1	Boston	Massachusetts	United States	02114
2	Clinical Research Site 2	Saint Paul	Minnesota	United States	55114

Sponsors and Collaborators

• Theracos

Investigators

• Study Director: J. P. Lock, M.D., Theracos Sub, LLC

Study Documents (Full-Text)

• Study Protocol - Aug 21, 2018
• Statistical Analysis Plan - May 31, 2019

More Information

Publications

None provided.

• Responsible Party: Theracos
• ClinicalTrials.gov Identifier: NCT03557658
• Other Study ID Numbers: THR-1442-C-455
• First Posted: Jun 15, 2018
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Bexagliflozin

Study Results

Participant Flow

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment	Total
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg	Total of all reporting groups
Overall Participants	8	8	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.1 (4.16)	59.9 (4.58)	58.5 (4.46)
Sex: Female, Male (Count of Participants)
Female	2 25%	2 25%	4 25%
Male	6 75%	6 75%	12 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 12.5%	1 6.3%
Not Hispanic or Latino	8 100%	6 75%	14 87.5%
Unknown or Not Reported	0 0%	1 12.5%	1 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 12.5%	1 6.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	7 87.5%	15 93.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Child-Pugh Total Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	0 (0)	8.3 (0.89)	4.13 (4.30)
Smoking Status (Count of Participants)
Current Smoker	2 25%	2 25%	4 25%
Former Smoker	3 37.5%	3 37.5%	6 37.5%
Non-Smoker	3 37.5%	3 37.5%	6 37.5%
Pack Years of Cigarette Smoking (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.2 (5.27)	13.2 (20.09)	9.23 (14.47)

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Plasma Concentration)
Description	Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) population included all subjects without major protocol violations who were dispensed the study drug and provided an observation for at least one primary PK endpoint.

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Measure Participants	8	8
Total Bexagliflozin	90.8 (34.0)	96.5 (37.3)
Unbound Bexagliflozin	6.0 (45.5)	6.6 (46.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function, Moderate Hepatic Impairment
	Comments	Geometric LS Mean was used as PK parameters for total bexagliflozin by hepatic function group.
	Type of Statistical Test	Equivalence
	Comments	The acceptance range for bioequivalence is 80.0 - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	106.22
	Confidence Interval	(2-Sided) 90%; 78.34 to 144.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point Estimate is the estimated ratio of exponentiated mean difference of log-transformed PK parameter from ANOVA. Confidence interval is obtained from ANOVA with hepatic function group as a fixed effect, and the subject as a random effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function, Moderate Hepatic Impairment
	Comments	Geometric LS Mean was used as PK parameters for unbound bexagliflozin by hepatic function group
	Type of Statistical Test	Equivalence
	Comments	The acceptance range for bioequivalence is 80.00 - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	110.84
	Confidence Interval	(2-Sided) 90%; 75.34 to 163.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point Estimate is the estimated ratio of exponentiated mean difference of log-transformed PK parameter from ANOVA. Confidence interval is obtained from ANOVA with hepatic function group as a fixed effect, and the subject as a random effect.

2. Primary Outcome

Title	Tmax (Time of Maximum Observed Plasma Concentration)
Description	Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Measure Participants	8	8
Total Bexagliflozin	3.00	3.00
Unbound Bexagliflozin	3.00	3.00

3. Primary Outcome

Title	T1/2 (Apparent Terminal Elimination Half-life)
Description	Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The adjusted r2 value for the regression for Subject 4551383007 (normal hepatic function group) was less than 0.7. The T1/2 was not estimated.

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Measure Participants	8	8
Total Bexagliflozin	9.4 (40.2)	9.5 (51.0)
Unbound Bexagliflozin	11.3 (44.1)	10.6 (37.7)

4. Primary Outcome

Title	AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Description	Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

The adjusted r2 value for the regression for Subject 4551383007 (normal hepatic function group) was less than 0.7. The AUC0-inf was not estimated.

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Measure Participants	8	8
Total Bexagliflozin	695.8 (25.3)	893.0 (32.2)
Unbound Bexagliflozin	47.9 (31.0)	63.3 (38.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function, Moderate Hepatic Impairment
	Comments	Geometric LS Mean was used as PK parameters for total bexagliflozin by hepatic function group
	Type of Statistical Test	Equivalence
	Comments	The acceptance range for bioequivalence is 80.00 - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	128.34
	Confidence Interval	(2-Sided) 90%; 99.98 to 164.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point Estimate is the estimated ratio of exponentiated mean difference of log-transformed PK parameter from ANOVA. Confidence interval is obtained from ANOVA with hepatic function group as a fixed effect, and the subject as a random effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function, Moderate Hepatic Impairment
	Comments	Geometric LS Mean was used as PK parameters for unbound bexagliflozin by hepatic function group
	Type of Statistical Test	Equivalence
	Comments	The acceptance range for bioequivalence is 80.00 - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	132.16
	Confidence Interval	(2-Sided) 90%; 96.46 to 181.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point Estimate is the estimated ratio of exponentiated mean difference of log-transformed PK parameter from ANOVA. Confidence interval is obtained from ANOVA with hepatic function group as a fixed effect, and the subject as a random effect.

5. Primary Outcome

Title	Urinary Glucose Excretion 0-48 Hours
Description	Pre-dose urine samples were collected from -12 to 0 h for baseline measurement of pharmacodynamic parameters. Post-dose urine samples were collected without preservative in four batches: 0 to 12 h, 12 to 24 h, 24 to 36h, and 36 to 48 h after dosing. Urine aliquots were prepared from well mixed collections for the assessment of pharmacodynamics.
Time Frame	0-48 hours

Outcome Measure Data

Analysis Population Description

The Pharmacodynamic (PD) Population included all subjects without major protocol violations who were dispensed the study drug and produced at least the first 12 h post-dose urine. The PD Population was used to summarize the PD parameters. One subject in the Normal Hepatic Function group did not have the urinary glucose concentration measurement on the 36 to 48-hour urine collection.

Arm/Group Title	Normal Hepatic Function	Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.	Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
Measure Participants	8	8
Pre-dose (-12 - 0 hours)	0.04 (0.045)	0.91 (2.464)
0 - 12 hours post-dose	37.76 (7.253)	29.57 (8.492)
12 - 24 hours post-dose	21.99 (5.780)	19.25 (6.311)
24 - 36 hours post-dose	26.76 (14.588)	20.96 (11.340)
36 - 48 hours post-dose	5.87 (4.785)	5.11 (5.165)
0 - 24 hours post-dose	59.75 (12.497)	48.82 (12.405)
0 - 48 hours post-dose	91.92 (28.142)	74.89 (25.410)

Adverse Events

Time Frame	The adverse event data were collected from Day 0 up to Day 16 after drug administration
Arm/Group Title	Normal Hepatic Function		Moderate Hepatic Impairment
Arm/Group Description	Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.		Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
All Cause Mortality
	Normal Hepatic Function		Moderate Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Normal Hepatic Function		Moderate Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Normal Hepatic Function		Moderate Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		3/8 (37.5%)
General disorders
Feeling abnormal	1/8 (12.5%)	1	0/8 (0%)	0
Fatigue	0/8 (0%)	0	1/8 (12.5%)	1
Vessel puncture site haemorrhage	0/8 (0%)	0	1/8 (12.5%)	1
Infections and infestations
Pneumonia	0/8 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Myalgia	1/8 (12.5%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Investigator does not have the right to publish trial results.