Study of TAK-071 in Healthy Participants and Participants With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability (BA) and Food Effect of TAK-071 in Healthy Participants
Condition: Alzheimer Disease; Healthy Volunteers
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: TAK-071; Donepezil; TAK-071 Placebo; Donepezil Placebo
Intervention description: TAK-071 capsules; Donepezil over-encapsulated tablet; TAK-071 placebo-matching capsules; Donepezil placebo-matching over-encapsulated tablet
Intervention MeSH terms: Donepezil
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 179.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug Therapy

Summary:

      The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of
      TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally
      in healthy participants and participants with mild cognitive impairment (MCI) or mild
      Alzheimer disease (AD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to
             30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years,
             inclusive (nonelderly at the time of informed consent and first study drug dose) for
             Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55
             to 90 years, inclusive, for participants in Cohort 16.

          2. For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in
             Japan of Japanese parents and Japanese grandparents and living no more than 10 years
             outside of Japan, with no significant change in lifestyle, including diet, while
             living outside of Japan.

          3. Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have
             Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26
             inclusive, respectively, and no biomarker data to contradict this diagnosis.
             Participants with documented diagnosis of MCI or mild AD must be receiving ongoing
             donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in
             (Day -1) or must consent to take donepezil dose titrated to at least 21 days of
             treatment with 10 mg QD prior to Check-in.

        Exclusion Criteria:

          1. Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16)
             neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal
             (GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality
             (other than the disease being studied), which may impact the ability of the
             participant to participate or potentially confound the study results.

          2. Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to
             15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled
             (hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in
             the study.

          3. Has a risk of suicide or suicidal ideation with intent and plan according to the
             investigator's clinical judgment (affirmative answer to questions 4 and 5 of the
             ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide
             attempt in the previous 6 months.

          4. Cohort 16 only: Any significant neurologic disease (other than suspected incipient or
             mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct
             dementia, Huntington disease, head trauma with clinically significant cognitive
             sequelae, or chronic central nervous system infection, per investigator discretion.

          5. Has current or recent (within 6 months) GI disease that would be expected to influence
             the absorption of drugs (ie, a history of malabsorption, any surgical intervention
             known to impact absorption [eg, bariatric surgery or bowel resection], esophageal
             reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per
             week] occurrence of heartburn).