A Single-Dose Study of the Pharmacokinetics of Vibegron (MK-4618) in Adults With Hepatic Insufficiency (MK-4618-013)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01737684
• Collaborator: (none)
• Enrollment: 16
• Arms: 3
• Actual Duration (Months): 4.9

Study Details

Study Description

Brief Summary

This study will investigate the pharmacokinetics of a single oral dose of vibegron (MK-4618) administered to participants with moderate hepatic insufficiency and healthy participants matched for age, gender, and body mass index (BMI). Participants may be enrolled with mild hepatic insufficiency.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: Vibegron	Phase 1

Detailed Description

This study is planned to be conducted in two parts. Part 1 of the study will include participants with moderate hepatic insufficiency and healthy participants. If Part 2 is conducted, Part 2 of the study will include participants with mild hepatic insufficiency.

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 Two-Part, Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-4618 in Patients With Hepatic Insufficiency
• Actual Study Start Date: Jan 15, 2013
• Actual Primary Completion Date: Jun 14, 2013
• Actual Study Completion Date: Jun 14, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants With Moderate Hepatic Insufficiency Participants with moderate hepatic insufficiency will receive a single oral dose of vibegron 100 mg.	Drug: Vibegron; 50 mg tablet, oral; Other Names: MK-4618
Experimental: Healthy Matched Control Participants Participants who are healthy will receive a single oral dose of vibegron 100 mg.	Drug: Vibegron; 50 mg tablet, oral; Other Names: MK-4618
Experimental: Participants With Mild Hepatic Insufficiency Participants with mild hepatic insufficiency will receive a single oral dose of vibegron 100 mg.	Drug: Vibegron; 50 mg tablet, oral; Other Names: MK-4618

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

Secondary Outcome Measures

1. Apparent Clearance (CL/F), Calculated as Dose/AUC0-∞, After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

2. Apparent Volume of Distribution During the Terminal Phase (Vd/F) After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

3. Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

4. Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

5. Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg [Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose]

   Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.

Eligibility Criteria

Criteria

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

Inclusion Criteria

For both healthy participants and participants with hepatic insufficiency:

• Continuous non-smokers who haven't used nicotine-containing products for at least 3 months prior to study drug administration

• Body mass index (BMI) ≤39 kg/m^2

• Good health based on medical history, physical examination, vital signs, laboratory safety tests, and electrocardiogram (ECG)

• Females of childbearing potential must be sexually inactive for 14 days prior to study drug administration and throughout study or use acceptable birth control method

• Females of non-childbearing potential must have undergone an acceptable sterilization procedure at least 6 months prior to Day 1 of study or be postmenopausal with amenorrhea for at least 1 year prior to Day 1

• Non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse during the trial and for 3 months after study drug administration

For participants with hepatic insufficiency only:

• Diagnosis of chronic, stable, hepatic insufficiency

• For Part 1 Participants: Child-Pugh scale range from 7 to 9

• For Part 2 Participants: Child-Pugh scale range from 5 to 6

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01737684
• Other Study ID Numbers: 4618-013
• First Posted: Nov 29, 2012
• Last Update Posted: Dec 24, 2018
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatic Insufficiency; Liver Failure; Urinary Bladder, Overactive

Study Results

Participant Flow

Pre-assignment Detail	This study was planned to be conducted in two parts. Part 1 was to include participants with moderate hepatic insufficiency and healthy participants. Part 2 was to include participants with mild hepatic insufficiency. After a review of the safety and pharmacokinetic data from Part 1, a decision was made not to conduct Part 2.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants	Participants With Mild Hepatic Insufficiencey
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants with mild hepatic insufficiency were to receive a single oral dose of vibegron 100 mg.
Period Title: Overall Study
STARTED	8	8	0
COMPLETED	8	8	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants	Total
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.	Total of all reporting groups
Overall Participants	8	8	16
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	58	54	56
Sex: Female, Male (Count of Participants)
Female	1 12.5%	1 12.5%	2 12.5%
Male	7 87.5%	7 87.5%	14 87.5%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population, which included the subset of participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Geometric Mean (95% Confidence Interval) [uM•hr]	4.10	3.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Moderate Hepatic Insufficiency, Healthy Matched Control Participants
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-squares mean ratio
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 90%; 0.96 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Apparent Clearance (CL/F), Calculated as Dose/AUC0-∞, After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population, which included participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	56.0 (31.2)	68.3 (36)

3. Secondary Outcome

Title	Apparent Volume of Distribution During the Terminal Phase (Vd/F) After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

PP population, which included participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [L]	7640 (33.3)	9120 (30.7)

4. Secondary Outcome

Title	Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

PP population, which included participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Geometric Mean (95% Confidence Interval) [nM]	378	281

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Moderate Hepatic Insufficiency, Healthy Matched Control Participants
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-squares mean ratio
	Estimated Value	1.35
	Confidence Interval	(2-Sided) 90%; 0.88 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

PP population, which included participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Median (Full Range) [hr]	1.00	1.50

6. Secondary Outcome

Title	Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg
Description	Blood samples were collected for determination of vibegron levels predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

PP population, which included participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Participants With Moderate Hepatic Insufficiency	Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.	Participants received a single oral dose of vibegron 100 mg on Day 1.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [hr]	94.54 (8.88)	92.48 (9.37)

Adverse Events

Time Frame	Up to 336 hours post-dose
Adverse Event Reporting Description	The All Subjects as Treated (AST) population, which consisted of all participants who received at least 1 dose of the investigational drug, was used for the safety analysis.
Arm/Group Title	Participants With Moderate Hepatic Insufficiency		Healthy Matched Control Participants
Arm/Group Description	Participants received a single oral dose of vibegron 100 mg on Day 1.		Participants received a single oral dose of vibegron 100 mg on Day 1.
All Cause Mortality
	Participants With Moderate Hepatic Insufficiency		Healthy Matched Control Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Participants With Moderate Hepatic Insufficiency		Healthy Matched Control Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Participants With Moderate Hepatic Insufficiency		Healthy Matched Control Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		1/8 (12.5%)
Vascular disorders
Flushing	0/8 (0%)	0	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication or presentation.