A Study of the Efficacy and Safety of Vibegron (MK-4618) in Participants With Overactive Bladder (OAB) (MK-4618-008)
This study has been completed.
Sponsor:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01314872
First received: March 11, 2011
Last updated: May 11, 2016
Last verified: May 2016
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Purpose
This is a 2-part study to assess if vibegron (MK-4618) reduces the number of daily urinations more effectively than placebo in participants with overactive bladder (OAB). The primary hypothesis of the base study is that administration of vibegron demonstrates a dose-related reduction, compared with placebo, in average number of daily micturitions in participants with OAB after 8 weeks of treatment.
| Condition | Intervention | Phase |
|---|---|---|
|
Urinary Bladder, Overactive |
Drug: Vibegron Drug: Tolterodine ER Drug: Placebo matching vibegron Drug: Placebo matching tolterodine ER |
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 A 52-week Extension to: 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:
- Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each micturition. The average daily number of micturitions was calculated as the total number of micturitions that occurred over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of daily micturitions that occurred during the week of placebo run-in prior to Week 0 visit.
- Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Part 1: up to 8 weeks; Part 2: up to 4 weeks. The time frame was an additional 2 weeks for participants not continuing to the Extension Study. ] [ Designated as safety issue: Yes ]An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
- Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE [ Time Frame: Part 1: up to 8 weeks; Part 2: up to 4 weeks ] [ Designated as safety issue: Yes ]An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
- Extension Study: Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Extension: up to 54 weeks (including 2-week follow-up) ] [ Designated as safety issue: Yes ]An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
- Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE [ Time Frame: Extension: up to 52 weeks ] [ Designated as safety issue: Yes ]An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Secondary Outcome Measures:
- Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
- Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
- Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of strong urge episodes that occurred during the week of placebo run-in prior to Week 0 visit.
- Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the daily occurrence of each micturition. The average daily number of micturitions was calculated as the total number of recorded micturitions that occurred during the 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
- Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each urge incontinence episode. The average daily number of urge incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
- Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
- Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 [ Time Frame: Baseline and Week 52 of Extension Study ] [ Designated as safety issue: No ]Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
| Enrollment: | 1395 |
| 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 |
|---|---|
|
Placebo Comparator: Part 1: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks.
|
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Part 1: vibegron 3 mg
Participants received one vibegron 3 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Part 1: vibegron 15 mg
Participants received one vibegron 15 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Part 1: vibegron 50 mg
Participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Part 1: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Active Comparator: Part 1: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks.
|
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
|
|
Experimental: Part 1: vibegron 50 mg + tolterodine ER 4 mg/vibegron 50 mg
Participants received one vibegron 50 mg tablet and one placebo matching vibegron tablet, taken orally each morning, for 8 weeks. They also received one tolterodine ER 4 mg capsule for the first 4 weeks and one placebo matching tolterodine ER capsule for the second 4 weeks, both taken orally each morning.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Placebo Comparator: Part 2: placebo
Participants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
|
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Part 2: vibegron 100 mg
Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Active Comparator: Part 2: tolterodine ER 4 mg
Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 4 weeks.
|
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
|
|
Experimental: Part 2: vibegron 100 mg + tolterodine ER 4 mg
Participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
|
|
Experimental: Extension Study: vibegron 50 mg
Participants in Base Study/Part 1 who received vibegron 50 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 3 mg received vibegron 50 mg in the Extension Study. Also, participants in Base Study/Part 1 who received vibegron 50 mg + tolterodine ER for 4 weeks, followed by vibegron 50 mg alone for 4 weeks, remained on vibegron 50 mg in the Extension Study. In the extension, participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Extension Study: vibegron 100 mg
Participants in Base Study/Part 1 or Part 2 who received vibegron 100 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received vibegron 15 mg received vibegron 100 mg in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 52 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Placebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
|
|
Experimental: Extension Study: tolterodine ER 4 mg
Participants in Base Study/Part 1 or Part 2 who received tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 1 who received placebo also received tolterodine ER 4 mg in the Extension Study. In the extension, participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 52 weeks.
|
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
Drug: Placebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
|
|
Experimental: Extension Study: vibegron 100 mg + tolterodine ER 4 mg
Participants in Base Study/Part 1 who received vibegron 100 mg + tolterodine ER 4 mg continued their treatment in the Extension Study. In addition, participants in Base Study/Part 2 who received placebo were assigned to the vibegron 100 mg + tolterodine ER 4 mg arm in the Extension Study. In the extension, participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 52 weeks.
|
Drug: Vibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
Other Name: MK-4618
Drug: Tolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
Other Name: Detrol®
|
Detailed Description:
All participants received placebo (run-in) for 1 week prior to randomization to Parts 1 and 2. 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 (Adult, Senior) |
| 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 vibegron (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
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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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01314872
Please refer to this study by its ClinicalTrials.gov identifier: NCT01314872
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme Corp. |
More Information
| Responsible Party: | Merck Sharp & Dohme Corp. |
| ClinicalTrials.gov Identifier: | NCT01314872 History of Changes |
| Other Study ID Numbers: | 4618-008 132241 2010-022121-15 2011-002533-18 |
| Study First Received: | March 11, 2011 |
| Results First Received: | May 11, 2016 |
| Last Updated: | May 11, 2016 |
| 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 Urinary Bladder Diseases Urologic Diseases Lower Urinary Tract Symptoms Urological Manifestations Signs and Symptoms Tolterodine Tartrate |
Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Urological Agents |
ClinicalTrials.gov processed this record on September 27, 2016