Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012)
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: MK-7622; Placebo; AChEI
Intervention description: MK-7622 capsule; Matching placebo to MK-7622 capsule; 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 240.0
Sex: All
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

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