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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

Primary Purpose

Alzheimer Disease, Healthy Volunteers

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

TAK-071

Donepezil

TAK-071 Placebo

Donepezil Placebo

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Drug Therapy

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.
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.
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:

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.
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.
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.
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.
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).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm 21

Arm 22

Arm 23

Arm 24

Arm 25

Arm 26

Arm 27

Arm 28

Arm 29

Arm 30

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

SRD: Placebo Cohorts 1-6, 18 and 19

SRD: Cohort 1: TAK-071 1 mg

SRD: Cohort 2: TAK-071 3 mg

SRD: Cohort 3: TAK-071 9 mg

SRD: Cohort 4: TAK-071 20 mg

SRD: Cohort 5: TAK-071 40 mg

SRD: Cohort 6: TAK-071 80 mg

MRD: Placebo Cohorts 7-9

MRD: Cohort 7: TAK-071 3 mg

MRD: Cohort 8: TAK-071 9 mg

MRD: Cohort 9: TAK-071 15 mg

MRD: TAK-071 Placebo Cohorts 10-12+Donepezil

MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg

MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg

MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg

MRD: Placebo Cohorts 13-15

MRD: Cohort 13: TAK-071 3 mg

MRD: Cohort 14: TAK-071 9 mg

MRD: Cohort 15: TAK-071 15 mg

Cohort 16

Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC

BA/Food Effect: Cohort 17 Sequence BCA

BA/Food Effect: Cohort 17 Sequence CAB

SRD: Cohort 18: TAK-071 120 mg

SRD: Cohort 19: TAK-071 160 mg

SRD: TAK-071 Placebo+Donepezil Placebo

SRD: TAK-071 Placebo+Donepezil

SRD: Cohort 20: TAK-071 40 mg+Donepezil

SRD: Cohort 21: TAK-071 60 mg+Donepezil

SRD: Cohort 22: TAK-071 80 mg+Donepizil

Arm Description

TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period.

TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants.

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.

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.

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.

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.

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

TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period.

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.

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.

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.

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.

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.

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.

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.

TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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]

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]

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]

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]

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]

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

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

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

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]

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

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

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

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

Secondary Outcome Measures

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CLR: Renal Clearance for TAK-071 MRD Japanese Participants

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

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

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

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

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

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

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

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

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.

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

Full Information

NCT ID

NCT02769065

First Posted

May 10, 2016

Last Updated

March 8, 2019

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT02769065

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Terminated

Why Stopped

Terminated prematurely as data from cohort no longer needed due to indication change.

Study Start Date

May 5, 2016 (Actual)

Primary Completion Date

June 8, 2017 (Actual)

Study Completion Date

June 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Healthy Volunteers

Keywords

Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

179 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SRD: Placebo Cohorts 1-6, 18 and 19

Arm Type

Placebo Comparator

Arm Description

TAK-071 placebo-matching capsules, orally, once on Day 1 to non-Japanese healthy participants in the single-rising dose (SRD) period.

Arm Title

SRD: Cohort 1: TAK-071 1 mg

Arm Type

Experimental

Arm Description

TAK-071 1 mg, capsule, orally, once on Day 1 to non-Japanese healthy participants.

Arm Title

SRD: Cohort 2: TAK-071 3 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: Cohort 3: TAK-071 9 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: Cohort 4: TAK-071 20 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: Cohort 5: TAK-071 40 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: Cohort 6: TAK-071 80 mg

Arm Type

Experimental

Arm Description

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

Arm Title

MRD: Placebo Cohorts 7-9

Arm Type

Placebo Comparator

Arm Description

TAK-071 placebo-matching capsule, orally, once on Day 1 to non-Japanese healthy participants in the multiple-rising dose (MRD) period.

Arm Title

MRD: Cohort 7: TAK-071 3 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 8: TAK-071 9 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 9: TAK-071 15 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: TAK-071 Placebo Cohorts 10-12+Donepezil

Arm Type

Placebo Comparator

Arm Description

Arm Title

MRD: Cohort 10: TAK-071 3 mg+Donepezil 5 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 11: TAK-071 9 mg + Donepezil 5 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 12: TAK-071 15 mg+Donepezil 5 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Placebo Cohorts 13-15

Arm Type

Experimental

Arm Description

TAK-071 placebo-matching capsule, orally, once on Day 1 to Japanese healthy participants.

Arm Title

MRD: Cohort 13: TAK-071 3 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 14: TAK-071 9 mg

Arm Type

Experimental

Arm Description

Arm Title

MRD: Cohort 15: TAK-071 15 mg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 16

Arm Type

Experimental

Arm Title

Bioavailability (BA)/Food Effect: Cohort 17 Sequence ABC

Arm Type

Experimental

Arm Description

Arm Title

BA/Food Effect: Cohort 17 Sequence BCA

Arm Type

Experimental

Arm Description

Arm Title

BA/Food Effect: Cohort 17 Sequence CAB

Arm Type

Experimental

Arm Description

Arm Title

SRD: Cohort 18: TAK-071 120 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: Cohort 19: TAK-071 160 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

SRD: TAK-071 Placebo+Donepezil Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

SRD: TAK-071 Placebo+Donepezil

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

SRD: Cohort 20: TAK-071 40 mg+Donepezil

Arm Type

Experimental

Arm Description

Arm Title

SRD: Cohort 21: TAK-071 60 mg+Donepezil

Arm Type

Experimental

Arm Description

Arm Title

SRD: Cohort 22: TAK-071 80 mg+Donepizil

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TAK-071

Intervention Description

TAK-071 capsules

Intervention Type

Drug

Intervention Name(s)

Donepezil

Intervention Description

Donepezil over-encapsulated tablet

Intervention Type

Drug

Intervention Name(s)

TAK-071 Placebo

Intervention Description

TAK-071 placebo-matching capsules

Intervention Type

Drug

Intervention Name(s)

Donepezil Placebo

Intervention Description

Donepezil placebo-matching over-encapsulated tablet

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Day 1 up to Day 41

Title

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

Description

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

Time Frame

Day 1 up to Day 41

Title

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

Description

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

Title

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

Description

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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: 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. 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. 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. 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. 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

City

Glendale

State/Province

California

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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