A Study of the Pharmacokinetics and Pharmacodynamics of Vibegron (MK-4618) in Women With Overactive Bladder (MK-4618-004)
Condition: Overactive Bladder; Overactive Urinary Bladder
MeSH terms: Urinary Bladder, Overactive
Intervention: Vibegron; Tolterodine ER; Placebo (vibegron); Placebo (tolterodine ER); Prophylactic Antibiotic
Intervention description: Tablet, 50 or 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.; Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.; Inactive agent in tablet form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.; Inactive agent in capsule form, oral administration, once daily, up to 5 weeks, based on treatment assignment in each treatment period.; 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 MeSH terms: Anti-Bacterial Agents; Tolterodine Tartrate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 4.0
Sex: Female
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

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