A Study of the Efficacy and Safety of MK-4618 in Patients With Overactive Bladder (OAB) (MK-4618-008 AM3 EXT1[AM2])

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01314872
First received: March 11, 2011
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

This is a 2-part study to assess if MK-4618 reduces the number of daily urinations more effectively than placebo in participants with overactive bladder (OAB).


Condition Intervention Phase
Urinary Bladder, Overactive
Drug: MK-4618 low-dose
Drug: MK-4618 mid-low dose
Drug: MK-4618 mid-high dose
Drug: tolterodine ER
Drug: Placebo for MK-4618
Drug: Placebo for tolterodine ER
Drug: MK-4618 high dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb Randomized, Placebo- and Active Comparator (Tolterodine)-Controlled, 2-Part Clinical Study of the Efficacy and Safety 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 Average Daily Micturitions [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Base Study: Number of Participants Who Experienced an Adverse Event (AE) and/ or Serious Adverse Event (SAE) [ Time Frame: Day 1, up to Week 8 ] [ Designated as safety issue: Yes ]
  • Extension: Number of Participants Who Discontinued the Study Due to an AE and/or SAE [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: Yes ]
  • Extension: Number of Participants Who Experienced an Adverse Event (AE) and/ or Serious Adverse Event (SAE) [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: Yes ]
  • Base Study: Number of Participants Who Discontinued the Study Due to an AE and/or SAE [ Time Frame: Day 1, up to Week 8 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from Baseline in Number of Urge Incontinence Episodes [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change from Baseline in Total Incontinence Episodes [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change from Baseline in Number of Strong Urge Episodes [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Extension: Change From Extension Baseline in Average Daily Micturitions [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: No ]
  • Extension: Change from Extension Baseline in Average Daily Urge Incontinence Episodes [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: No ]
  • Extension: Change from Extension Baseline in Average Daily Total Incontinence Episodes [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: No ]
  • Extension: Change from Extension Baseline in Average Daily Strong Urge Episodes [ Time Frame: Day 1 of Week 8, up to Week 60 ] [ Designated as safety issue: No ]

Enrollment: 1307
Study Start Date: March 2011
Study Completion Date: October 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Base Study Part 1: MK-4618 low-dose
Participants may be randomized to receive MK-4618 low-dose + placebo for MK-4618 + placebo for tolterodine extended release (ER)
Drug: MK-4618 low-dose
One low-dose tablet taken orally each morning, for 8 weeks.
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Experimental: Base Study Part 1: MK-4618 mid-low dose
Participants may be randomized to receive MK-4618 mid low-dose + placebo for MK-4618 + placebo for tolterodine ER
Drug: MK-4618 mid-low dose
One mid-low dose tablet taken orally each morning, for 8 weeks.
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Experimental: Base Study Part 1: MK-4618 mid-high dose
Participants may be randomized to receive MK-4618 mid high-dose + placebo for MK-4618 + placebo for tolterodine ER
Drug: MK-4618 mid-high dose
One mid-high dose tablet taken orally each morning, for up to 60 weeks.
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Experimental: Base Study Part 1 and Part 2: MK-4618 high dose
Participants may be randomized to receive MK-4618 high dose + placebo for tolterodine ER
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Drug: MK-4618 high dose
Two tablets taken orally each morning, for up to 60 weeks.
Active Comparator: Base Study Part 1 and Part 2: tolterodine ER
Participants may be randomized to receive tolterodine ER + two tablets of placebo for MK-4618
Drug: tolterodine ER
One 4 mg capsule taken orally each morning, for up to 60 weeks.
Other Name: Detrol®
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Experimental: Base Study Part 1: MK-4618 mid-high dose + tolterodine ER
Participants may be randomized to receive MK-4618 mid-high dose + tolterodine ER + placebo for MK-4618 for 4 weeks, and continue with MK-4618 mid-high dose + placebo for MK-4618 + placebo for tolterodine ER for an additional 4 weeks
Drug: MK-4618 mid-high dose
One mid-high dose tablet taken orally each morning, for up to 60 weeks.
Drug: tolterodine ER
One 4 mg capsule taken orally each morning, for up to 60 weeks.
Other Name: Detrol®
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Placebo Comparator: Base Study Part 1 and Part 2: placebo
Participants may be randomized to receive two placebo tablets for MK-4618 + placebo for tolterodine ER
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Experimental: Extension: MK-4618 high-dose
Participants may continue to receive or be assigned to receive MK-4618 high-dose + placebo for tolterodine ER for the duration of the study; up to 60 weeks.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.
Drug: MK-4618 high dose
Two tablets taken orally each morning, for up to 60 weeks.
Experimental: Extension: MK-4618 high-dose + tolterodine ER
Participants may continue to receive or be assigned to receive high-dose MK-4618 + tolterodine ER for the duration of the study; up to 60 weeks.
Drug: tolterodine ER
One 4 mg capsule taken orally each morning, for up to 60 weeks.
Other Name: Detrol®
Drug: MK-4618 high dose
Two tablets taken orally each morning, for up to 60 weeks.
Active Comparator: Extension: tolterodine ER
Participants may continue to receive or be assigned to receive tolterodine ER + 2 placebo tablets for MK-4618 for the duration of the study; up to 60 weeks
Drug: tolterodine ER
One 4 mg capsule taken orally each morning, for up to 60 weeks.
Other Name: Detrol®
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Experimental: Base Study Part 2: MK-4618 high-dose + tolterodine ER
Participants may be randomized to receive MK-4618 high dose + tolterodine ER for 4 weeks
Drug: tolterodine ER
One 4 mg capsule taken orally each morning, for up to 60 weeks.
Other Name: Detrol®
Drug: MK-4618 high dose
Two tablets taken orally each morning, for up to 60 weeks.
Experimental: Extension: MK-4618 mid-high dose
Participants may continue to receive or be assigned to receive MK 4618 mid-high dose + placebo for tolterodine ER + placebo for MK-4618 for the duration of the extension, up to 60 weeks
Drug: MK-4618 mid-high dose
One mid-high dose tablet taken orally each morning, for up to 60 weeks.
Drug: Placebo for MK-4618
One or two tablets taken orally each morning for dose-duration of matched drug.
Drug: Placebo for tolterodine ER
One capsule taken orally each morning for dose-duration of matched drug.

Detailed Description:

Participants who complete the base study may be screened for a year-long, multicenter extension for assessment of long-term safety and efficacy

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • If participant is of reproductive potential, must agree to remain abstinent or use (or have his/her partner use) 2 acceptable methods of birth control within the projected duration of the study
  • Clinical history of OAB for at least 3 months and meets either the OAB wet or OAB dry criteria
  • Is able to read, understand and complete questionnaires and voiding diaries without assistance
  • Is ambulatory and in good general physical and mental health
  • No clinically significant electrocardiogram or laboratory abnormality

Exclusion Criteria:

  • If female, is currently pregnant or breast-feeding, or expecting to conceive within the projected duration of the study
  • Evidence of diabetes insipidus, uncontrolled hyperglycemia or uncontrolled hypercalcemia
  • Allergy, intolerance, or history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of tolterodine ER or MK-4618 formulation; or has a history or active diagnosis of any condition contraindicated in the tolterodine ER prescribing label
  • Has lower urinary tract pathology that could be responsible for urgency, frequency, or incontinence
  • History of injury, surgery, or neurodegenerative diseases (e.g., multiple sclerosis) that could affect the lower urinary tract or its nerve supply
  • History of continual urine leakage
  • Surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months
  • Known history of elevated postvoid residual
  • Bladder training or electrostimulation within 2 weeks or is planning to initiate either procedure during the study
  • Active or recurrent (>6 episodes per year) urinary tract infections
  • Current hematuria
  • Required use of an indwelling catheter or requires intermittent catheterization
  • History of fecal incontinence
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01314872     History of Changes
Other Study ID Numbers: 4618-008
Study First Received: March 11, 2011
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Overactive bladder
MK-4618
tolterodine

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

ClinicalTrials.gov processed this record on October 21, 2014