Overactive Bladder
Conditions
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.
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.
Interventions
DRUGVibegron
50 mg tablet, oral
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Moderate Hepatic Insufficiency Participants received a single oral dose of vibegron 100 mg on Day 1. | 8 |
| Healthy Matched Control Participants Participants received a single oral dose of vibegron 100 mg on Day 1. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Participants With Moderate Hepatic Insufficiency | Healthy Matched Control Participants | Total |
|---|---|---|---|
| Age, Continuous | 58 Years | 54 Years | 56 Years |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Insufficiency | Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg | 4.10 uM•hr |
| Healthy Matched Control Participants | Area Under the Concentration Time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg | 3.23 uM•hr |
90% CI: [0.96, 1.67]ANCOVA
Secondary
Apparent Clearance (CL/F), Calculated as Dose/AUC0-∞, After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Insufficiency | 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 |
| Healthy Matched Control Participants | Apparent Clearance (CL/F), Calculated as Dose/AUC0-∞, After a Single Oral Dose of Vibegron 100 mg | 68.3 L/hr | Geometric Coefficient of Variation 36 |
Secondary
Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Insufficiency | Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg | 94.54 hr | Geometric Coefficient of Variation 8.88 |
| Healthy Matched Control Participants | Apparent Terminal Half-life (t½) After a Single Oral Dose of Vibegron 100 mg | 92.48 hr | Geometric Coefficient of Variation 9.37 |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vd/F) After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Insufficiency | 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 |
| Healthy Matched Control Participants | Apparent Volume of Distribution During the Terminal Phase (Vd/F) After a Single Oral Dose of Vibegron 100 mg | 9120 L | Geometric Coefficient of Variation 30.7 |
Secondary
Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Insufficiency | Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 378 nM |
| Healthy Matched Control Participants | Maximum Observed Plasma Drug Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 281 nM |
90% CI: [0.88, 2.06]ANCOVA
Secondary
Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Moderate Hepatic Insufficiency | Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg | 1.00 hr |
| Healthy Matched Control Participants | Time to Maximum Observed Plasma Drug Concentration (Tmax) After a Single Oral Dose of Vibegron 100 mg | 1.50 hr |