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

NCT01852110 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: 7622-0122013-000937-11MK-7622-012
• Study Type: interventional
• Target: 240
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at Week 12 (Stage 1, MK-7622 45 mg Versus Placebo)

  Mean change from baseline at week 12 was assessed for ADAS-Cog11 score. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in Alzheimer's Disease (AD): speech; speech comprehension; word finding; word recall; object/finger naming; orientation; obeying commands; ideational praxis; constructional praxis; word recognition; and remembering instruction. For each metric, scores range from 0 (no impairment) to (depending on the metric) either 5 (8 metrics), 8, 10, or 12 (1 metric each); higher scores indicate more severe impairment. Individual scores sum to a total ADAS-Cog11 score, ranging from 0-70. Higher total scores indicate greater cognitive impairment and AD severity. Further, increases in AD severity over time would be reflected by increases in ADAS-Cog11 score.

  Baseline and week 12

• Change From Baseline in ADAS-Cog11 Score at Week 12 (Stage 2, MK-7622 45 mg and 15 mg Versus Placebo)

  Mean change from baseline at week 12 was assessed for ADAS-Cog11 score. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in Alzheimer's Disease (AD): speech; speech comprehension; word finding; word recall; object/finger naming; orientation; obeying commands; ideational praxis; constructional praxis; word recognition; and remembering instruction. For each metric, scores range from 0 (no impairment) to (depending on the metric) either 5 (8 metrics), 8, 10, or 12 (1 metric each); higher scores indicate more severe impairment. Individual scores sum to a total ADAS-Cog11 score, ranging from 0-70. Higher total scores indicate greater cognitive impairment and AD severity. Further, increases in AD severity over time would be reflected by increases in ADAS-Cog11 score.

  Baseline and week 12

• Number of Participants Experiencing an Adverse Event (AE)

  The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.

  Up to 26 weeks

• Number of Participants Who Discontinued Study Drug Due to an AE

  The number of participants discontinuing study drug due to an AE was assessed.

  Up to 24 weeks

Secondary Outcomes (3)

• 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)

  Baseline and week 24

• Change From Baseline in Composite Cognition Score-3 Domain (CCS-3D) at Week 12 (Stage 1, MK-7622 45 mg Versus Placebo)

  Baseline and week 12

• Change From Baseline in CCS-3D at Week 12 (Stage 2, MK-7622 45 mg and 15 mg Versus Placebo)

  Baseline and Week 12

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: MK-7622; Drug: AChEI

Placebo (Stage 1)

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: AChEI

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

EXPERIMENTAL

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

Drug: MK-7622; Drug: AChEI

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

EXPERIMENTAL

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

Drug: MK-7622; Drug: AChEI

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

EXPERIMENTAL

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.

Drug: MK-7622; Drug: AChEI

Placebo (Stage 2)

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: AChEI

Interventions

MK-7622 DRUG

MK-7622 capsule

MK-7622 High Dose - 45 mg (Stage 1); MK-7622 High Dose - 45 mg (Stage 2); MK-7622 Low Dose - 5 mg (Stage 2); MK-7622 Mid Dose - 15 mg (Stage 2)

Placebo DRUG

Matching placebo to MK-7622 capsule

Placebo (Stage 1); Placebo (Stage 2)

AChEI 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 1); MK-7622 High Dose - 45 mg (Stage 2); MK-7622 Low Dose - 5 mg (Stage 2); MK-7622 Mid Dose - 15 mg (Stage 2); Placebo (Stage 1); Placebo (Stage 2)

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 29955661 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Stage 1 Interim analysis of efficacy met the clinical criteria for early trial termination (futility). As a result, the trial was terminated at Stage 1 and did not proceed to Stage 2.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Study Start: October 22, 2013
• Primary Completion: April 11, 2016
• Study Completion: April 11, 2016
• Last Updated: September 18, 2018
• Results First Posted: February 7, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share