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

This study has been terminated.
(This study was terminated early due to insufficient recruitment.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01500382
First received: December 22, 2011
Last updated: August 2, 2016
Last verified: August 2016
  Purpose

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.


Condition Intervention Phase
Overactive Bladder
Overactive Urinary Bladder
Drug: Vibegron
Drug: Tolterodine ER
Other: Placebo (vibegron)
Other: Placebo (tolterodine ER)
Drug: Prophylactic Antibiotic
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo and Active-Comparator Controlled Multiple-Dose Study to Evaluate the Pharmacokinetics and Pharmacodynamics of MK-4618 in Patients With Overactive Bladder

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Fold-change From Baseline in Maximum Cystometric Capacity Post-dose on Day 7 [ Time Frame: Baseline (pre-dose Day 1) and Day 7 (post-dose) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Use of Study Drug Due to an AE [ Time Frame: Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Fold-change From Baseline in Volume of Urine at First Desire to Void Post-dose on Day 7 [ Time Frame: Baseline (pre-dose Day 1) and Day 7 (post-dose) ] [ Designated as safety issue: No ]
    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.


Enrollment: 4
Study Start Date: February 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Vibegron
Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.
Other Name: MK-4618
Drug: Tolterodine ER
Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.
Other Name: Detrol LA™
Other: Placebo (vibegron)
Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
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.
Drug: 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.
Other Names:
  • Levaquin
  • Biocef
  • Ed A-Ceph
  • Keflex
  • Keftab
  • Panixine DisperDose
  • Zartan
Experimental: 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.
Drug: Vibegron
Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.
Other Name: MK-4618
Other: Placebo (vibegron)
Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
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.
Drug: 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.
Other Names:
  • Levaquin
  • Biocef
  • Ed A-Ceph
  • Keflex
  • Keftab
  • Panixine DisperDose
  • Zartan
Active Comparator: 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.
Drug: Tolterodine ER
Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.
Other Name: Detrol LA™
Other: Placebo (vibegron)
Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
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.
Drug: 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.
Other Names:
  • Levaquin
  • Biocef
  • Ed A-Ceph
  • Keflex
  • Keftab
  • Panixine DisperDose
  • Zartan
Experimental: 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.
Drug: Vibegron
Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.
Other Name: MK-4618
Other: Placebo (vibegron)
Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.
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.
Drug: 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.
Other Names:
  • Levaquin
  • Biocef
  • Ed A-Ceph
  • Keflex
  • Keftab
  • Panixine DisperDose
  • Zartan

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.
  Eligibility

Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500382

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01500382     History of Changes
Other Study ID Numbers: 4618-004 
Study First Received: December 22, 2011
Results First Received: August 2, 2016
Last Updated: August 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Anti-Bacterial Agents
Antibiotics, Antitubercular
Tolterodine Tartrate
Anti-Infective Agents
Antitubercular Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents

ClinicalTrials.gov processed this record on September 29, 2016