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

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

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).

Study Overview

• Status: Terminated
• Conditions: Alzheimer Disease; Healthy Volunteers
• Intervention / Treatment: Drug: TAK-071 Placebo; Drug: TAK-071; Drug: Donepezil; Drug: Donepezil Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

30

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: SRD: Placebo Cohorts 1-6, 18 and 19; TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules
Experimental: SRD: Cohort 1: TAK-071 1 mg; TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 2: TAK-071 3 mg; TAK-071 3 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety, tolerability and pharmacokinetic (PK) data from cohort 1.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 3: TAK-071 9 mg; TAK-071 9 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK and 12-hour CSF PK data.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 4: TAK-071 20 mg; TAK-071 20 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on the 24-hour post-dose safety and tolerability data from previous cohort.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 5: TAK-071 40 mg; TAK-071 40 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 will be based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 4.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 6: TAK-071 80 mg; TAK-071 80 mg capsules, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 5	Drug: TAK-071; TAK-071 capsules
Placebo Comparator: MRD: Placebo Cohorts 7-9; TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules
Experimental: MRD: Cohort 7: TAK-071 3 mg; TAK-071 3 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability from Cohort 4 and the 24-hour preliminary plasma PK and 12-hour CSF PK data from Cohort 3.	Drug: TAK-071; TAK-071 capsules
Experimental: MRD: Cohort 8: TAK-071 9 mg; TAK-071 9 mg capsules, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants. Dose of TAK-071 was based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.	Drug: TAK-071; TAK-071 capsules
Experimental: MRD: Cohort 9: TAK-071 15 mg; TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to non-Japanese healthy participants. Dose of TAK-071 will be based on safety, tolerability and available PK data arising from the ongoing SRD part and previous MRD cohort.	Drug: TAK-071; TAK-071 capsules
Placebo Comparator: MRD: TAK-071 Placebo Cohorts 10-12+Donepezil; TAK-071 placebo-matching capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg; TAK-071 3 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 7.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg; TAK-071 9 mg capsules, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 8.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg; TAK-071 15 mg capsule, orally, once daily along with donepezil 5 mg, tablets, orally, once daily from Day 1 up to Day 21 to non-Japanese healthy participants who were pre-treated with donepezil 5 mg, tablet, once daily for 3 weeks prior to administration of TAK-071. Dose of TAK-071 was same as the dose used in MRD Cohort 9.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: MRD: Placebo Cohorts 13-15; TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules
Experimental: MRD: Cohort 13: TAK-071 3 mg; TAK-071 3 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 7.	Drug: TAK-071; TAK-071 capsules
Experimental: MRD: Cohort 14: TAK-071 9 mg; TAK-071 9 mg capsule or matching placebo, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 8.	Drug: TAK-071; TAK-071 capsules
Experimental: MRD: Cohort 15: TAK-071 15 mg; TAK-071 15 mg capsule, orally, once on Day 1, followed by a washout period of 7 days, then TAK-071 once daily for 21 days to Japanese healthy participants. Dose of TAK-071 was same as the dose used in MRD Cohort 9.	Drug: TAK-071; TAK-071 capsules
Experimental: Cohort 16	Drug: TAK-071; TAK-071 capsules
Experimental: Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC; A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 1, followed by B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 2, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.	Drug: TAK-071; TAK-071 capsules
Experimental: BA/Food Effect: Cohort 17 Sequence BCA; B: TAK-071 10 mg tablet, orally, once on Day 1 in the fasted state in Period 1, followed by C: TAK-071 10 mg tablet, orally, once on Day 1 in the Fed state in Period 2, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.	Drug: TAK-071; TAK-071 capsules
Experimental: BA/Food Effect: Cohort 17 Sequence CAB; C: TAK-071 10 mg tablet, orally, once on Day 1 in the fed state in Period 1, followed by A: TAK-071 10 mg capsule, orally once on Day 1 in the fasted state in Period 2, followed by B: TAK-20 10 mg tablet, orally, once on Day 1 in the fasted state in Period 3 in non-Japanese healthy participants. There was a 21-day washout after each period.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 18: TAK-071 120 mg; TAK-071 120 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 6.	Drug: TAK-071; TAK-071 capsules
Experimental: SRD: Cohort 19: TAK-071 160 mg; TAK-071 160 mg capsule, orally, once on Day 1 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 18.	Drug: TAK-071; TAK-071 capsules
Placebo Comparator: SRD: TAK-071 Placebo+Donepezil Placebo; TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil placebo-matching tablet, orally on Day 2 to non-Japanese healthy participants.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules; Drug: Donepezil Placebo; Donepezil placebo-matching over-encapsulated tablet
Placebo Comparator: SRD: TAK-071 Placebo+Donepezil; TAK-071 placebo-matching capsule, orally, once on Day 1 followed by donepezil 10 mg tablet, orally, on Day 2 to non-Japanese healthy participants.	Drug: TAK-071 Placebo; TAK-071 placebo-matching capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: SRD: Cohort 20: TAK-071 40 mg+Donepezil; TAK-071 40 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety, tolerability, and preliminary plasma PK data from Cohort 19.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: SRD: Cohort 21: TAK-071 60 mg+Donepezil; TAK-071 60 mg capsule, orally, once on Day 1 followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 20.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet
Experimental: SRD: Cohort 22: TAK-071 80 mg+Donepizil; TAK-071 80 mg capsule, orally, once on Day 1, followed by donepezil 10 mg, tablets, orally, once on Day 2 to non-Japanese healthy participants. Dose of TAK-071 was based on 24-hour safety and tolerability data from Cohort 21.	Drug: TAK-071; TAK-071 capsules; Drug: Donepezil; Donepezil over-encapsulated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
AUC∞: 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
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
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		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		Pre-dose on Day 1 and at multiple time points [up to 168 hours] post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Accumulation Ratio Based on AUCτ (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
Accumulation Ratio Based on AUCτ (Rac[AUC]) for TAK-071 MRD Japanese Participants		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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		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.	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	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

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2016
• Primary Completion (Actual): June 8, 2017
• Study Completion (Actual): June 8, 2017

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: TAK-071-1001; U1111-1176-7435 (Registry Identifier: WHO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No