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

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:

Genetics Home Reference related topics: hereditary multiple exostoses

MedlinePlus related topics: Overactive Bladder Urine and Urination

Drug Information available for: Tolterodine Tolterodine tartrate

U.S. FDA Resources

Further study details as provided by Merck:

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 ]

Estimated Enrollment:	1295
Study Start Date:	March 2011
Estimated Study Completion Date:	November 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

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01314872 History of Changes
Other Study ID Numbers:	4618-008
Study First Received:	March 11, 2011
Last Updated:	December 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Overactive bladder
MK-4618
tolterodine

Additional relevant MeSH terms:

Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Tolterodine
Phenylpropanolamine
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on June 18, 2013