Trial Outcomes & Findings for A Single-Dose Study of the Pharmacokinetics of Vibegron (MK-4618) in Adults With Hepatic Insufficiency (MK-4618-013) (NCT NCT01737684)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Results posted on

2018-12-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Participants With Moderate Hepatic Insufficiency Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Total n=16 Participants Total of all reporting groups
Age, Continuous	58 Years n=5 Participants	54 Years n=7 Participants	56 Years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg	4.10 uM•hr Interval 3.25 to 5.16	3.23 uM•hr Interval 2.56 to 4.07

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Apparent Clearance (CL/F), Calculated as Dose/AUC0-∞, After a Single Oral Dose of Vibegron 100 mg	56.0 L/hr Geometric Coefficient of Variation 31.2	68.3 L/hr Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Apparent Volume of Distribution During the Terminal Phase (Vd/F) After a Single Oral Dose of Vibegron 100 mg	7640 L Geometric Coefficient of Variation 33.3	9120 L Geometric Coefficient of Variation 30.7

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg	378 nM Interval 265.0 to 540.0	281 nM Interval 197.0 to 401.0

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg	1.00 hr Interval 0.5 to 3.0	1.50 hr Interval 0.5 to 4.0

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours postdose

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Participants With Moderate Hepatic Insufficiency n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 Participants Participants received a single oral dose of vibegron 100 mg on Day 1.
Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg	94.54 hr Geometric Coefficient of Variation 8.88	92.48 hr Geometric Coefficient of Variation 9.37

Adverse Events

Participants With Moderate Hepatic Insufficiency

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Matched Control Participants

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Participants With Moderate Hepatic Insufficiency n=8 participants at risk Participants received a single oral dose of vibegron 100 mg on Day 1.	Healthy Matched Control Participants n=8 participants at risk Participants received a single oral dose of vibegron 100 mg on Day 1.
Vascular disorders Flushing	0.00% 0/8 • Up to 336 hours post-dose 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.	12.5% 1/8 • Number of events 1 • Up to 336 hours post-dose 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.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER