A Study of the Pharmacokinetics and Pharmacodynamics of MK4618 in Women With Overactive Bladder (MK-4618-004 AM1)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01500382
First received: December 22, 2011
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The study is designed to investigate the effects of an investigational drug, MK-4618 on maximum urinary bladder capacity 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.


Condition Intervention Phase
Overactive Bladder
Overactive Urinary Bladder
Drug: MK-4618
Drug: Tolterodine ER
Drug: MK-1468 and Tolterodine ER
Other: Placebo (MK-4618)
Other: Placebo (Tolterodine ER)
Drug: Prophylactic Antibiotic
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics 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:
  • Change from baseline in maximum cystometric capacity at post-dose on Day 7 in each treatment period [ Time Frame: At baseline and post dose at Day 7 of each treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline of volume of urine at first desire to void [ Time Frame: At baseline and post dose on Day 7 in each treatment period ] [ Designated as safety issue: No ]

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: MK-4618
Each participant will be randomized to receive one of the following treatments in each of 2 treatment periods: MK-4618 100 milligrams (mg) plus matching tolterodine placebo, tolterodine ER 4 mg plus matching MK-4618 placebo, co-administration of MK-4618 100 mg and tolterodine ER 4 mg, or matching placebo).
Drug: MK-4618
Tablet, 100 mg, once daily, for up to 10 days based on treatment assignments and 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: Tolterodine ER
Each participant will be randomized to receive one of the following treatments in each of 2 treatment periods: MK-4618 100 milligrams (mg) plus matching tolterodine placebo, tolterodine ER 4 mg plus matching MK-4618 placebo, co-administration of MK-4618 100 mg and tolterodine ER 4 mg, or matching placebo).
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 (MK-4618)
Inactive agent in tablet 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
MK-4618 and tolterodine ER
Each participant will be randomized to receive one of the following treatments in each of 2 treatment periods: MK-4618 100 milligrams (mg) plus matching tolterodine placebo, tolterodine ER 4 mg plus matching MK-4618 placebo, co-administration of MK-4618 100 mg and tolterodine ER 4 mg, or matching placebo).
Drug: MK-4618
Tablet, 100 mg, once daily, for up to 10 days based on treatment assignments and treatment period.
Drug: Tolterodine ER
Capsule, 4 mg, once daily, for up to 10 days based on treatment assignment and treatment period.
Other Name: Detrol LA™
Drug: MK-1468 and Tolterodine ER
Co-administration of MK-4618 (Tablet, 100 mg, once daily, for up to 10 days) and Tolterodine ER (Capsule, 4 mg, once daily, for up to 10 days)
Other Name: Detrol LA (tolterodine ER)
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
Placebo Comparator: Placebo
Each participant will be randomized to receive one of the following treatments in each of 2 treatment periods: MK-4618 100 milligrams (mg) plus matching tolterodine placebo, tolterodine ER 4 mg plus matching MK-4618 placebo, co-administration of MK-4618 100 mg and tolterodine ER 4 mg, or matching placebo).
Other: Placebo (MK-4618)
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
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
No Contacts or Locations Provided
  More Information

No publications provided

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
Last Updated: February 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anti-Bacterial Agents
Cephalexin
Antibiotics, Antitubercular
Tolterodine
Phenylpropanolamine
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nasal Decongestants

ClinicalTrials.gov processed this record on April 15, 2014