Overactive Bladder
Conditions
Brief summary
This study will investigate the impact of impaired renal function on the plasma pharmacokinetics of vibegron (MK-4618) to guide use of vibegron in clinical trials in participants with overactive bladder and to guide recommendations on potential dosing adjustments for individuals with varying degrees of renal impairment.
Interventions
DRUGVibegron 100 mg
Vibegron tablets, orally, on Day 1
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
- Renal Impaired Patients * Body mass index (BMI) ≤40 kg/m\^2 * Clinical diagnosis of renal insufficiency * Stable baseline health Inclusion Criteria - Healthy Subjects \- Stable baseline health
Exclusion criteria
- Renal Impaired Patients * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary disease * History of recent stroke, chronic seizures, or major neurological disorder * Demonstrated or suspected renal artery stenosis * Renal transplant or nephrectomy * History of cancer excepting certain skin or cervical cancers or cancers that were successfully treated 10 or more years prior to screening * History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food * Unable to refrain from or anticipates the use of any medication including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of study drug, throughout the study, and until the post study visit * Unable to avoid taking diuretics within 4 hours prior to dosing and 4 hours post dosing; must be on a stable dose for at least approximately 2 weeks (or 5 half-lives of the compound, whichever is longer) * Unwilling to refrain from consuming any food or drink/beverage containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats 2 weeks prior to dosing until the post-study visit * Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day * Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day * Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) within 4 weeks prior to administration of study drug * Plasma donation within 7 days prior to administration of study drug * Current regular user (including recreational use) of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months * Nursing mother * Participation in another investigational study within 4 weeks of study enrollment
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 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine AUC0-∞ after a single oral dose of vibegron 100 mg. |
| Maximum Plasma 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 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine Cmax after a single oral dose of vibegron 100 mg. |
| Apparent Total Body Clearance (CL/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 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine CL/F after a single oral dose of vibegron 100 mg. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Severe Renal Insufficiency Participants received a single oral dose of vibegron 100 mg on Day 1. | 8 |
| Participants With Moderate Renal Insufficiency Participants received a single oral dose of vibegron 100 mg on Day 1. | 8 |
| Participants With Mild Renal 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 | 32 |
Baseline characteristics
| Characteristic | Participants With Severe Renal Insufficiency | Participants With Moderate Renal Insufficiency | Participants With Mild Renal Insufficiency | Healthy Matched Control Participants | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65 Years | 64 Years | 66 Years | 57 Years | 63 Years |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 4 / 8 | 3 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg
Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine CL/F after a single oral dose of vibegron 100 mg.
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 Severe Renal Insufficiency | Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg | 35.5 L/hr |
| Participants With Moderate Renal Insufficiency | Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg | 31.5 L/hr |
| Participants With Mild Renal Insufficiency | Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg | 43.6 L/hr |
| Healthy Matched Control Participants | Apparent Total Body Clearance (CL/F) After a Single Oral Dose of Vibegron 100 mg | 64.9 L/hr |
90% CI: [0.41, 0.74]ANCOVA
90% CI: [0.36, 0.65]ANCOVA
90% CI: [0.5, 0.9]ANCOVA
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 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine AUC0-∞ after a single oral dose of vibegron 100 mg.
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) |
|---|---|---|
| Participants With Severe Renal Insufficiency | Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg | 6337.17 nM•hr |
| Participants With Moderate Renal Insufficiency | Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg | 7137.53 nM•hr |
| Participants With Mild Renal Insufficiency | Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) After a Single Oral Dose of Vibegron 100 mg | 5156.07 nM•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 | 3466.04 nM•hr |
90% CI: [1.36, 2.46]ANCOVA
90% CI: [1.55, 2.74]ANCOVA
90% CI: [1.11, 2]ANCOVA
Primary
Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg
Blood samples were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 216, and 336 hours after dosing in order to determine Cmax after a single oral dose of vibegron 100 mg.
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 Severe Renal Insufficiency | Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 342.83 nM |
| Participants With Moderate Renal Insufficiency | Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 404.50 nM |
| Participants With Mild Renal Insufficiency | Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 473.01 nM |
| Healthy Matched Control Participants | Maximum Plasma Concentration (Cmax) After a Single Oral Dose of Vibegron 100 mg | 240.80 nM |
90% CI: [0.89, 2.27]ANCOVA
90% CI: [1.07, 2.63]ANCOVA
90% CI: [1.23, 3.13]ANCOVA