A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)

Merck Sharp & Dohme (MSD)

Status and phase

Terminated

Phase 1

Conditions

Overactive Urinary Bladder

Overactive Bladder

Treatments

Other: Placebo (vibegron)

Drug: Vibegron

Other: Placebo (tolterodine ER)

Drug: Tolterodine ER

Drug: Prophylactic Antibiotic

Study type

Interventional

Funder types

Industry

Identifiers

NCT01500382

4618-004

Details and patient eligibility

About

The study is designed to investigate the effects of the investigational drug vibegron (MK-4618) compared to placebo on maximum urinary bladder capacity in women with overactive bladder. The study will also evaluate the safety and tolerability of multiple oral doses of vibegron in women with overactive bladder. Overactive bladder is best described as urgency and frequency of urination, with or without involuntary urination and/or the need to awaken during the night to urinate.

The primary efficacy hypothesis is that vibegron is superior to placebo with respect to change from baseline in maximum cystometric capacity at 2 hours postdose on Day 7 (i.e., steady state) in participants with overactive bladder. A true mean increase (vibegron/placebo) of 25% in bladder volume is expected.

The primary safety hypothesis is that administration of multiple oral doses of vibegron is sufficiently well-tolerated in participants with overactive bladder, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.

Full description

Participants will be randomized in each of 2 treatment periods to 1 of 4 possible treatments, which will be administered in double-dummy fashion, and participants will undergo urodynamic procedures prior to dosing on Day 1 and after 7 days of treatment.

Enrollment

4 patients

Sex

Female

Ages

40 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Non-child bearing potential (status post menopausal or post hysterectomy,oophorectomy or tubal ligation). If of reproductive potential, must be non-pregnant (confirmed via blood test) and agree to use (and/or have their partner use) two acceptable methods of birth control beginning at least 2 weeks prior to administration of the first dose of study drug,throughout the study (including washout intervals between treatment periods/panels) and until at least 2 weeks after administration of the last dose of study drug in the last treatment period.
Body mass index (BMI) of ≤40 kg/m^2 (ie, not morbidly obese)
Clinical history of overactive bladder symptoms (OAB) for at least 3 months
Capable of completing an accurate daily diary for reporting purposes

Exclusion criteria

Mentally or legally incapacitated, such as significant emotional problems (other than situational depression) or diagnosed with a significant psychiatric disorder during the past 5-10 years
Other types of urinary incontinence (ie,stress or mixed)
History (current or past)of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain or Stage III or greater pelvic organ prolapse
Other types of kidney/urinary bladder disease/obstruction or infection. Participants with with a history of uncomplicated kidney stones may be enrolled in the study at the discretion of the investigator
Inability to control bowel movements
History of narrow angle glaucoma, immunocompromise, stroke, chronic seizures, major neurological disorders and/or other serious and chronic organ-system health conditions (ie, heart disease)
Urinary catheter, either permanent or intermittent placement
Failure to meet medication profile requirements or directives required for study eligibility
Condition for which there is a warning, contraindication, or precaution against the use of tolterodine ER or anticipates the use of prescription medications contraindicated with the use of tolterodine ER
Daily alcohol or caffeine intake exceeds study requirements (for alcohol: defined as greater than 2 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; and for caffeine: defined as greater than 3 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee,tea, cola, or other caffeinated beverages (ie, Red Bull) per day
Inability to refrain from smoking throughout the study's duration
Illicit drug use
Recent surgery or recent participation in another clinical trial
Severe, frequent allergies or history of life-threatening reactions or intolerability to prescription or non prescription medications or food
Intended or unintended extended absence or exposure to significant change in time zone or sleep schedule (ie, transmeridian travel or shift work) that will interfere with accurate completion of scheduled daily diary entries

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

4 participants in 4 patient groups

Vibegron 100 mg + tolterodine ER 4 mg → placebo

Experimental group

Description:

During Treatment Period 1, participants will receive 7 days of once-daily vibegron 100 mg and tolterodine extended-release (ER) 4 mg. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER.

Treatment:

Drug: Prophylactic Antibiotic

Other: Placebo (tolterodine ER)

Drug: Tolterodine ER

Drug: Vibegron

Other: Placebo (vibegron)

Placebo → vibegron 100 mg

Experimental group

Description:

During Treatment Period 1, participants will receive 7 days of once-daily placebo to match vibegron and placebo to match tolterodine ER. Participants will then complete a 2-week single-blind double-dummy placebo washout period prior to Treatment Period 2. During Treatment Period 2, participants will receive 7 days of once-daily vibegron 100 mg and placebo to match tolterodine ER.

Treatment:

Drug: Prophylactic Antibiotic

Other: Placebo (tolterodine ER)

Drug: Vibegron

Other: Placebo (vibegron)

Placebo → tolterodine ER 4 mg

Active Comparator group

Description:

Treatment:

Drug: Prophylactic Antibiotic

Other: Placebo (tolterodine ER)

Drug: Tolterodine ER