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Efficacy and Safety of MK-7622 as Adjunct Therapy to Donepezil in Participants With Alzheimer's Disease (MK-7622-012)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01852110
First received: May 8, 2013
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of this multicenter trial is to assess the efficacy and safety of MK-7622 compared with placebo as adjunctive therapy to donepezil for the symptomatic treatment of participants with mild to moderate Alzheimer's Disease (AD). The trial consists of two stages: Stage 1 and Stage 2. Participants in Stage 1 will be randomized to receive either placebo or MK-7622 45 mg once daily. In Stage 2, participants will be randomized to receive either placebo, or MK-7622 5, 15 or 45 mg once daily. Participants will be enrolled in only one stage. Interim analyses will be performed in both Stage 1 and Stage 2 to determine whether the trial should continue. Duration of each stage is approximately 26 weeks; all participants receive placebo at some time during the trial. The primary study hypotheses are the following: Stage 1 - MK-7622 45 mg once daily is superior to placebo in improving cognition in participants with mild to moderate AD as assessed by mean change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Week 12; Stage 2 - At least one of the top two doses of MK-7622 (15 mg once daily, 45 mg once daily) is superior to placebo in improving cognition in participants with mild to moderate AD as assessed by mean change from baseline in ADAS-Cog11 at Week 12.


Condition Intervention Phase
Alzheimer's Disease
Drug: MK-7622
Drug: Placebo
Drug: Donepezil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Seamless Phase IIa/IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial to Evaluate the Efficacy and Safety of MK-7622 as an Adjunctive Therapy to Donepezil for Symptomatic Treatment in Subjects With Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from baseline in ADAS-Cog11 score at Week 12 (Stage 1, MK-7622 45 mg versus placebo) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in ADAS-Cog11 score at Week 12 (Stage 2, MK-7622 45 mg and 15 mg versus placebo) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) at Week 24 (combining Stage 1 and 2, MK-7622 45 mg versus placebo) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Composite Cognition Score-3 Domain (CCS-3D) at Week 12 (Stage 1, MK-7622 45 mg versus placebo) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in CCS-3D at Week 12 (Stage 2, MK-7622 45 mg and 15 mg versus placebo) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 830
Study Start Date: October 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-7622 High Dose - 45 mg (Stage 1)
Dose titration to single 45 mg MK-7622 capsule once daily, taken orally: - 15 mg MK-7622 once daily for 1 week - 30 mg MK-7622 once daily for 1 week - 45 mg MK-7622 once daily for remainder of treatment. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: MK-7622
MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician
Placebo Comparator: Placebo (Stage 1)
Matching placebo to MK-7622 capsule once daily, taken orally. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: Placebo
Matching placebo to MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician
Experimental: MK-7622 Low Dose - 5 mg (Stage 2)
Single 5 mg MK-7622 capsule once daily, taken orally. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: MK-7622
MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician
Experimental: MK-7622 Mid Dose - 15 mg (Stage 2)
Single 15 mg MK-7622 capsule once daily, taken orally. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: MK-7622
MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician
Experimental: MK-7622 High Dose - 45 mg (Stage 2)
Dose titration to single 45 mg MK-7622 capsule once daily, taken orally: - 15 mg MK-7622 once daily for 1 week - 30 mg MK-7622 once daily for 1 week - 45 mg MK-7622 once daily for remainder of treatment. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: MK-7622
MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician
Placebo Comparator: Placebo (Stage 2)
Matching placebo to MK-7622 capsule once daily, taken orally. Duration of each study stage is approximately 26 weeks; all participants receive placebo at some time during the trial.
Drug: Placebo
Matching placebo to MK-7622 capsule
Drug: Donepezil
Donepezil 10 mg/day, as prescribed by the participant's primary care physician

Detailed Description:

If double-blind treatment dose is not tolerated during first 2 weeks, participant will be discontinued. After first 2 weeks, if dose is not tolerated regimen may be modified according to defined algorithm, beginning with administration of reduced dose for 2 weeks, then rechallenge at original dose, if tolerability issues diminish at reduced dose.

  Eligibility

Ages Eligible for Study:   55 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)

criteria for AD

  • AD is of mild to moderate severity
  • Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the participant well
  • On a stable daily dose of 10 mg donepezil, for at least three months before Screening, and willing to remain on the same dose for the duration of the trial
  • Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
  • Participant must have a reliable and competent trial partner/caregiver who must have a close relationship with the subject

Exclusion Criteria:

  • History of stroke
  • Evidence of a neurological disorder other than the disease being studied (ie, probable AD)
  • History of seizures or epilepsy within the last 5 years before Screening
  • Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission for >2 years
  • Participant is at imminent risk of self-harm or of harm to others
  • History of alcoholism or drug dependency/abuse within the last 5 years before Screening
  • Participant is unwilling or not eligible to undergo a magnetic resonance imaging (MRI) scan
  • History of hepatitis or liver disease that has been active within the six months prior to Screening Visit
  • Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the participant. Controlled co-morbid conditions are not exclusionary if stable within three months of the Screening Visit
  • History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year posttherapy
  • Clinically significant vitamin B12 deficiency, or increased thyroid stimulating hormone (TSH) in the six months before Screening
  • Major surgery within 3 months of Screening
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852110

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 40 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Additional Information:
No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01852110     History of Changes
Other Study ID Numbers: 7622-012, 2013-000937-11
Study First Received: May 8, 2013
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014