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

Phase 1TerminatedNCT02769065

Takeda179 enrolled

Overview

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).

TAK-071 was being tested to find a safe and well-tolerated dose in healthy participants (non-Japanese and Japanese) and participants with MCI or mild AD (non-Japanese). The study enrolled 179 participants. The study consisted of 4 parts: Single-rising dose (SRD) part (Cohorts 1-6, and 18-22), multiple-rising dose (MRD) part (Cohorts 7-15), Cohort 16 with 2-arm parallel design, and Cohort 17 relative bioavailability and food effect 3 period crossover design. Participants in each cohort were randomized to receive treatment with TAK-071 or matching placebo using drug-in-capsule (DIC) in the morning following a minimum fast of 8 hours. In Cohort 16, participants were assigned to 1 of 2 possible treatments, TAK-071 or matching placebo. In Cohort 17, participants were assigned to 1 of 3 treatment sequences (ABC, BCA, or CAB) with treatment A being fasted state and capsule formulation, treatment B being fasted state and tablet formulation, and treatment C being fed state and tablet formulation. In Cohorts 20-22, participants were administered as a single dose of TAK-071 or placebo on Day 1, and a single dose of donepezil or placebo approximately 24 hours later on Day 2. This multi-center trial was conducted in United States. The overall time to participate in this study was approximately 41 days. Participants made multiple visits to the clinic and were also contacted for the follow-up through the telephone.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

179

Conditions

Alzheimer Disease Healthy Volunteers

Interventions

TAK-071DRUG

TAK-071 capsules

DonepezilDRUG

Donepezil over-encapsulated tablet

TAK-071 PlaceboDRUG

TAK-071 placebo-matching capsules

Donepezil Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (1)

Unnamed facility

Glendale, California, United States

Outcomes

Primary Outcomes

Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs or gets worse after receiving study drug.

Time frame: Day 1 up to Day 41

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post-dose

Clinical laboratory tests included serum chemistry, hematology, coagulation and urinalysis. ULN=upper limit of normal range.

Time frame: Day 1 up to Day 41

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose

Vital Sign measurements included systolic blood pressure (SBP), diastolic blood presssure (DBP), pulse, temperature, orthostatic SBP, orthostatic DBP and orthostatic pulse.

Time frame: Day 1 up to Day 41

Percentage of Participants Who Meet the Markedly Abnormal Criteria for 12-lead Electrocardiogram (ECG) Parameters at Least Once Post-dose

A standard 12-lead electrocardiogram (ECG) was performed. The percentage of participants with markedly abnormal ECG findings during the study.

Time frame: Day 1 up to Day 41

Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Data from ClinicalTrials.gov

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Donepezil placebo-matching over-encapsulated tablet

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]

Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]

Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 21]

Time frame: Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8]

Time frame: Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28]

Time frame: Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Non-Japanese Participants [Day 1]

Time frame: Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose

AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Secondary Outcomes

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and multiple timepoints (up to 24 hrs) post-dose for Cohorts 7 and 8 and Pre-dose on Day 1 and multiple timepoints (up to 96 hrs) post-dose for Cohort 9

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose and Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese

Time frame: Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose

CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect

Time frame: Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose

Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil

Time frame: Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose

Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9

Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose

Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose

Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose for Cohorts 7 and 8 and Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose for Cohort 9

Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose

Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose

AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose

AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8, and pre-dose on Day 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9

AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose

Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 and multiple time points (up to 96 hours) post-dose for Cohort 9

Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose

CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants

Time frame: Pre-dose on Days 1 and 21 and at multiple time points (up to 24 hours) post-dose for Cohorts 7 and 8 and Pre-dose on Days 1 and 28 multiple time points (up to 96 hours) post-dose for Cohort 9

CLR: Renal Clearance for TAK-071 MRD Japanese Participants

Time frame: Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose and pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose

CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071

Time frame: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose

CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071

Time frame: Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose

CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071

Time frame: Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose

CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071

Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose

Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071

Time frame: Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071

Time frame: Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants

Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants

Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil

Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Ratio of Geometric Mean of Cmax for Donepezil After 21 Daily Doses of TAK-071

A linear mixed effect model on the natural log-transformed parameters was performed with day as a fixed effect and participant as a random effect. Ratio is the exponentiated geometric mean value Day 21/Day -1 on the original scale.

Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose

Ratio of Geometric Mean of AUC(0-24) for Donepezil After 21 Daily Doses of TAK-071

Time frame: Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose