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

Healthy Volunteers Clinical Trial

Official title:

A Phase 1 Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Oral Doses of TAK-071 in Healthy Subjects and Subjects With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability and Food Effect of TAK-071 in Healthy Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02769065
• Other study ID #: TAK-071-1001
• Secondary ID: U1111-1176-7435
• Status: Terminated
• Phase: Phase 1
• Start date: May 5, 2016
• Est. completion date: June 8, 2017

Study information

• Verified date: March 2019
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 179
• Est. completion date: June 8, 2017
• Est. primary completion date: June 8, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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).

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Healthy Volunteers

Intervention

Drug:
• TAK-071
TAK-071 capsules
• Donepezil
Donepezil over-encapsulated tablet
• TAK-071 Placebo
TAK-071 placebo-matching capsules
• Donepezil Placebo
Donepezil placebo-matching over-encapsulated tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 up to Day 41
Primary	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.	Day 1 up to Day 41
Primary	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.	Day 1 up to Day 41
Primary	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.	Day 1 up to Day 41
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 21]		Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 8]		Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 28]		Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 8]		Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Japanese Participants [Day 28]		Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 MRD Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Primary	Tmax: Time of First Occurrence of Cmax for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 Single-Rising Dose (SRD) Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 Multiple-Rising Dose (MRD) Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 21]		Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 8]		Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 28]		Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 8]		Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Japanese Participants [Day 28]		Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 MRD Non-Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	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		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	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]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	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]		Pre-dose on Day 21 and multiple time points (up to 24 hours) post-dose
Primary	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]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	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]		Pre-dose on Day 8 and multiple time points (up to 24 hour) post-dose
Primary	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]		Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Primary	AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 1]		Pre-dose on Day 1 and multiple time points (up to 96 hours) post-dose
Primary	AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 8]		Pre-dose on Day 8 and multiple time points (up to 24 hours) post-dose
Primary	AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-071 MRD Japanese Participants [Day 28]		Pre-dose on Day 28 and multiple time points (up to 24 hours) post-dose
Primary	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]		Pre-dose on Day 1 and multiple time points (up to 24 hours) post-dose
Primary	AUC8: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Primary	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		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Primary	AUC8: 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		Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Primary	AUC8: 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		Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Secondary	AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese Participants		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
Secondary	AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Japanese Participants		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
Secondary	AUClast: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-071 MRD Non-Japanese		Pre-dose on Day 1 and at multiple time points (up to 24 hours) post-dose
Secondary	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		Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Secondary	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		Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Secondary	Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	Terminal Disposition Phase Half-life (t1/2z) for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Secondary	Terminal Disposition Phase Half-life (t1/2z) for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil		Pre-dose on Day 1 and multiple time points (up to 168 hours) post-dose
Secondary	CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	CL/F: Apparent Clearance After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Secondary	CL/F: Apparent Clearance After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071+Donepezil		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 Relative Bioavailability and Food Effect		Pre-dose on Day 21 and multiple time points (up to 168 hours) post-dose
Secondary	Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-071 SRD Non-Japanese Participants TAK-071 + Donepezil		Pre-dose on Day 1 and at multiple time points (up to 168 hours) post-dose
Secondary	Accumulation Ratio Based on AUCt (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants		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
Secondary	Accumulation Ratio Based on AUCt (Rac[AUC]) for TAK-071 MRD Japanese Participants		Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Secondary	Accumulation Ratio Based on AUCt (Rac[AUC]) for TAK-071 MRD Non-Japanese Participants		Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
Secondary	Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants		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
Secondary	Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Japanese Participants		Pre-dose on Day 28 and at multiple time points [up to 24 hours] post-dose
Secondary	Accumulation Ratio Based on Plasma Cmax (Rac[Cmax]) for TAK-071 MRD Non-Japanese Participants		Pre-dose on Day 21 and at multiple time points [up to 24 hours] post-dose
Secondary	AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
Secondary	AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants		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
Secondary	AEt: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants		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
Secondary	Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points (up to 96 hours) post-dose
Secondary	Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Non-Japanese Participants		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
Secondary	Fet: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time t for TAK-071 MRD Japanese Participants		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
Secondary	CLR: Renal Clearance for TAK-071 SRD Non-Japanese Participants		Pre-dose on Day 1 and at multiple time points [up to 96 hours] post-dose
Secondary	CLR: Renal Clearance for TAK-071 MRD Non-Japanese Participants		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
Secondary	CLR: Renal Clearance for TAK-071 MRD Japanese Participants		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
Secondary	CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071		Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
Secondary	CSF Cmax: Maximum Observed Concentration in Cerebrospinal Fluid (CSF) for TAK-071		Pre-dose on Day 28 and at multiple time points (up to 36 hours) post-dose
Secondary	CSF AUC(0-12): Area Under the CSF Concentration-time Curve From Time 0 to 12 Hours for TAK-071		Pre-dose on Day 1 and at multiple time points (up to 12 hours) post-dose
Secondary	CSF AUC(0-36): Area Under the CSF Concentration-time Curve From Time 0 to 36 Hours for TAK-071		Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose
Secondary	Ratio of CSF AUC(0-12) to the Plasma AUC(0-12) for TAK-071		Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose
Secondary	Ratio of CSF AUC(0-36) to the Plasma AUC(0-36) for TAK-071		Pre-dose on Day 28 and multiple time points (up to 36 hours) post-dose Cohort 9
Secondary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Donepezil MRD Non-Japanese Participants		Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Secondary	Cmax: Maximum Observed Plasma Concentration for Donepezil MRD Non-Japanese Participants		Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Secondary	AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Donepezil		Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Secondary	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.	Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose
Secondary	Ratio of Geometric Mean of AUC(0-24) 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.	Pre-dose on Days -1 and 21 and multiple time points (up to 24 hours) post-dose