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

NCT ID: NCT02769065

Last Updated: 2019-06-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-05
• Study Completion Date: 2017-06-08

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.

Conditions

Alzheimer Disease; Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

SRD: Cohort 1: TAK-071 1 mg

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

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: PLACEBO_COMPARATOR

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: PLACEBO_COMPARATOR

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

MRD: Placebo Cohorts 13-15

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

Group Type: EXPERIMENTAL

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Cohort 16

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

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.

Group Type: PLACEBO_COMPARATOR

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

Donepezil Placebo

Intervention Type: DRUG

Donepezil placebo-matching over-encapsulated tablet

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.

Group Type: PLACEBO_COMPARATOR

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

TAK-071 Placebo

Intervention Type: DRUG

TAK-071 placebo-matching capsules

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

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.

Group Type: EXPERIMENTAL

TAK-071

Intervention Type: DRUG

TAK-071 capsules

Donepezil

Intervention Type: DRUG

Donepezil over-encapsulated tablet

Interventions

TAK-071

TAK-071 capsules

Intervention Type: DRUG

Donepezil

Donepezil over-encapsulated tablet

Intervention Type: DRUG

TAK-071 Placebo

TAK-071 placebo-matching capsules

Intervention Type: DRUG

Donepezil Placebo

Donepezil placebo-matching over-encapsulated tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years, inclusive (nonelderly at the time of informed consent and first study drug dose) for Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55 to 90 years, inclusive, for participants in Cohort 16.

2. For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in Japan of Japanese parents and Japanese grandparents and living no more than 10 years outside of Japan, with no significant change in lifestyle, including diet, while living outside of Japan.

3. Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26 inclusive, respectively, and no biomarker data to contradict this diagnosis. Participants with documented diagnosis of MCI or mild AD must be receiving ongoing donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in (Day -1) or must consent to take donepezil dose titrated to at least 21 days of treatment with 10 mg QD prior to Check-in.

Exclusion Criteria

1. Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16) neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.

2. Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to 15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled (hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in the study.

3. Has a risk of suicide or suicidal ideation with intent and plan according to the investigator's clinical judgment (affirmative answer to questions 4 and 5 of the ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.

4. Cohort 16 only: Any significant neurologic disease (other than suspected incipient or mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct dementia, Huntington disease, head trauma with clinically significant cognitive sequelae, or chronic central nervous system infection, per investigator discretion.

5. Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption [eg, bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per week] occurrence of heartburn).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Glendale, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1176-7435

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-071-1001

Identifier Type: -

Identifier Source: org_study_id