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

NCT ID: NCT01852110

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-22
• Study Completion Date: 2016-04-11

Brief Summary

The purpose of this multicenter trial is to assess the efficacy and safety of MK-7622 compared with placebo as adjunctive therapy to acetylcholinesterase inhibitors (AChEIs) 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. In Stage 1, participants 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 (dose: 5, 15 or 45 mg once daily). Participants will be enrolled in only one stage; the duration of each stage is approximately 26 weeks. Interim analyses will be performed in both Stage 1 and Stage 2 to determine whether the trial should continue. The primary study hypotheses are the following: Stage 1 - MK-7622 45 mg once daily is superior to placebo with respect to 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 with respect to improving cognition in participants with mild to moderate AD as assessed by mean change from baseline in ADAS-Cog11 at Week 12.

Detailed Description

If the double-blind treatment dose is not tolerated during the first 2 weeks, the participant will be discontinued. After the first 2 weeks, if the dose is not tolerated, the regimen may be modified according to a defined algorithm. Specifically, the participant will begin administration of a reduced dose for up to 2 weeks, followed by a re-challenge at the original dose only if tolerability issues diminish or resolve at the reduced dose.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MK-7622 High Dose - 45 mg (Stage 1)

Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.

Group Type: EXPERIMENTAL

MK-7622

Intervention Type: DRUG

MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

Placebo (Stage 1)

Matching placebo to MK-7622 capsule once daily, taken orally.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo to MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

MK-7622 Low Dose - 5 mg (Stage 2)

Single 5 mg MK-7622 capsule once daily, taken orally.

Group Type: EXPERIMENTAL

MK-7622

Intervention Type: DRUG

MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

MK-7622 Mid Dose - 15 mg (Stage 2)

Single 15 mg MK-7622 capsule once daily, taken orally.

Group Type: EXPERIMENTAL

MK-7622

Intervention Type: DRUG

MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

MK-7622 High Dose - 45 mg (Stage 2)

Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.

Group Type: EXPERIMENTAL

MK-7622

Intervention Type: DRUG

MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

Placebo (Stage 2)

Matching placebo to MK-7622 capsule once daily, taken orally.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo to MK-7622 capsule

AChEI

Intervention Type: DRUG

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

Interventions

MK-7622

MK-7622 capsule

Intervention Type: DRUG

Placebo

Matching placebo to MK-7622 capsule

Intervention Type: DRUG

AChEI

One of the following AChEIs, as prescribed by the participant's primary care physician:

Donepezil: 10 mg total daily dose, administered orally

Rivastigmine: 9.5 or 13.3 mg/24 hours, administered by transdermal patch; or 6-12 mg total daily dose administered orally

Galantamine: 16-24 mg total daily dose, administered orally

Intervention Type: DRUG

Eligibility 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 and effective daily dose of AChEI (either donepezil, rivastigmine, or galantamine), for at least two months before Screening, and willing to remain on the same dose for the duration of the trial. Effective doses are considered to be: donepezil, 10 mg total daily dose administered orally; rivastigmine, 9.5 or 13.3 mg/24 hours administered by transdermal patch or 6-12 mg total daily dose administered orally; galantamine, 16-24 mg total daily dose administered orally
• 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
• Have a reliable and competent trial partner who must have a close relationship with the subject

Exclusion Criteria

• History of clinically significant stroke
• Evidence of a neurological disorder other than the disease being studied (i.e., 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
• 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
• Does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of Screening and is unwilling or not eligible to undergo an MRI scan at Screening
• 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 post-therapy
• Clinically significant vitamin B12 deficiency, or increased thyroid stimulating hormone (TSH) in the six months before Screening
• Major surgery within 3 months of Screening

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Voss T, Li J, Cummings J, Farlow M, Assaid C, Froman S, Leibensperger H, Snow-Adami L, McMahon KB, Egan M, Michelson D. Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease. Alzheimers Dement (N Y). 2018 Apr 26;4:173-181. doi: 10.1016/j.trci.2018.03.004. eCollection 2018.

Reference Type: RESULT

PMID: 29955661 (View on PubMed)

Other Identifiers

2013-000937-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-7622-012

Identifier Type: OTHER

Identifier Source: secondary_id

7622-012

Identifier Type: -

Identifier Source: org_study_id