Clinical trial NCT01500382: A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Overactive Bladder
Overactive Urinary Bladder
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-12-28
Enrollment: 4
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Fold-change From Baseline in Maximum Cystometric Capacity Post-dose on Day 7
timeFrame: Baseline (pre-dose Day 1) and Day 7 (post-dose)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)
measure: Number of Participants Who Discontinued Use of Study Drug Due to an AE
timeFrame: Up to 6 weeks (up to 3 weeks in Period 1 and up to 3 weeks in Period 2)
Secondary outcomes:
measure: Fold-change From Baseline in Volume of Urine at First Desire to Void Post-dose on Day 7
timeFrame: Baseline (pre-dose Day 1) and Day 7 (post-dose)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: