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

NCT ID: NCT01500382

Last Updated: 2018-12-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-27
• Study Completion Date: 2013-01-02

Brief Summary

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.

Detailed 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.

Conditions

Overactive Bladder; Overactive Urinary Bladder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Vibegron 100 mg + tolterodine ER 4 mg → placebo

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.

Tolterodine ER

Intervention Type: DRUG

Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.

Placebo (vibegron)

Intervention Type: OTHER

Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Placebo (tolterodine ER)

Intervention Type: OTHER

Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Prophylactic Antibiotic

Intervention Type: DRUG

A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.

Placebo → vibegron 100 mg

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.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.

Placebo (vibegron)

Intervention Type: OTHER

Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Placebo (tolterodine ER)

Intervention Type: OTHER

Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Prophylactic Antibiotic

Intervention Type: DRUG

A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.

Placebo → tolterodine ER 4 mg

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 tolterodine 4 mg and placebo to match vibegron.

Group Type: ACTIVE_COMPARATOR

Tolterodine ER

Intervention Type: DRUG

Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.

Placebo (vibegron)

Intervention Type: OTHER

Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Placebo (tolterodine ER)

Intervention Type: OTHER

Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Prophylactic Antibiotic

Intervention Type: DRUG

A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.

Placebo → vibegron 50 mg

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 50 mg and placebo to match tolterodine ER.

Group Type: EXPERIMENTAL

Vibegron

Intervention Type: DRUG

Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.

Placebo (vibegron)

Intervention Type: OTHER

Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Placebo (tolterodine ER)

Intervention Type: OTHER

Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Prophylactic Antibiotic

Intervention Type: DRUG

A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.

Interventions

Vibegron

Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.

Intervention Type: DRUG

Tolterodine ER

Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.

Intervention Type: DRUG

Placebo (vibegron)

Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Intervention Type: OTHER

Placebo (tolterodine ER)

Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.

Intervention Type: OTHER

Prophylactic Antibiotic

A pre-procedural prophylactic antibiotic (ie, levofloxacin 250 mg, cephalexin) administered orally, 30 minutes prior to each scheduled urodynamic study intervention. It is up to the discretion of the Investigator, based on study protocol recommendations, as to which type of antibiotic may be administered.

Intervention Type: DRUG

Other Intervention Names

MK-4618; Detrol LA™; Levaquin; Biocef; Ed A-Ceph; Keflex; Keftab; Panixine DisperDose; Zartan

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

4618-004

Identifier Type: -

Identifier Source: org_study_id