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

NCT01500382 | Terminated Phase 1 Results

• 1 other identifier: 4618-004
• Study Type: interventional
• Target: 4
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Overactive Bladder; Overactive Urinary Bladder

Outcome Measures

Primary Outcomes (3)

• Fold-change From Baseline in Maximum Cystometric Capacity Post-dose on Day 7

  Filling cystometry procedures were performed pre-dose on Day 1 and post-dose on Day 7 in each treatment period. Individual values in fold-change from baseline and post-dose on Day 7 will be natural log-transformed and evaluated with a linear mixed effects model having period and treatment as fixed effects and participant as a random effect.

  Baseline (pre-dose Day 1) and Day 7 (post-dose)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.

  Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)

• Number of Participants Who Discontinued Use of Study Drug Due to an AE

  An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. The number of participants who discontinued study drug due to an AE were reported.

  Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)

Secondary Outcomes (1)

• Fold-change From Baseline in Volume of Urine at First Desire to Void Post-dose on Day 7

  Baseline (pre-dose Day 1) and Day 7 (post-dose)

Study Arms (4)

Vibegron 100 mg + tolterodine ER 4 mg → placebo

EXPERIMENTAL

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.

Drug: Vibegron; Drug: Tolterodine ER; Other: Placebo (vibegron); Other: Placebo (tolterodine ER); Drug: Prophylactic Antibiotic

Placebo → vibegron 100 mg

EXPERIMENTAL

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.

Drug: Vibegron; Other: Placebo (vibegron); Other: Placebo (tolterodine ER); Drug: Prophylactic Antibiotic

Placebo → tolterodine ER 4 mg

ACTIVE COMPARATOR

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.

Drug: Tolterodine ER; Other: Placebo (vibegron); Other: Placebo (tolterodine ER); Drug: Prophylactic Antibiotic

Placebo → vibegron 50 mg

EXPERIMENTAL

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.

Drug: Vibegron; Other: Placebo (vibegron); Other: Placebo (tolterodine ER); Drug: Prophylactic Antibiotic

Interventions

Vibegron DRUG

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

Also known as: MK-4618

Placebo → vibegron 100 mg; Placebo → vibegron 50 mg; Vibegron 100 mg + tolterodine ER 4 mg → placebo

Tolterodine ER DRUG

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

Also known as: Detrol LA™

Placebo → tolterodine ER 4 mg; Vibegron 100 mg + tolterodine ER 4 mg → placebo

Placebo (vibegron) 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 4 mg; Placebo → vibegron 100 mg; Placebo → vibegron 50 mg; Vibegron 100 mg + tolterodine ER 4 mg → placebo

Placebo (tolterodine ER) OTHER

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

Placebo → tolterodine ER 4 mg; Placebo → vibegron 100 mg; Placebo → vibegron 50 mg; Vibegron 100 mg + tolterodine ER 4 mg → placebo

Prophylactic Antibiotic 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.

Also known as: Levaquin, Biocef, Ed A-Ceph, Keflex, Keftab, Panixine DisperDose, Zartan

Placebo → tolterodine ER 4 mg; Placebo → vibegron 100 mg; Placebo → vibegron 50 mg; Vibegron 100 mg + tolterodine ER 4 mg → placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

N-(4-((5-(hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo(1,2-a)pyrimidine-6-carboxamide; Tolterodine Tartrate; Chemoprevention; Levofloxacin; Cephalexin

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols; Drug Therapy; Therapeutics; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds

Limitations and Caveats

This study was terminated early due to insufficient recruitment. Only four participants in total participated in the study with three completing and one discontinuation.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: February 27, 2012
• Primary Completion: January 2, 2013
• Study Completion: January 2, 2013
• Last Updated: December 24, 2018
• Results First Posted: September 26, 2016

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share