TAK-071 Scopolamine-Induced Cognitive Impairment Study

NCT02918266 | Terminated Phase 1 Results

• 2 other identifiers: TAK-071-1002U1111-1184-2278
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of a single oral dose of TAK-071 on the attenuation of cognitive deficit induced by scopolamine as measured by Groton Maze Learning Test (GMLT) (total number of errors).

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Part 2: Change From Baseline in Total Number of Errors on the Groton Maze Learning Test (GMLT) at 2 Hours Post-Scopolamine Dose on Day 2

  Baseline, 2 hours post scopolamine dose on Day 2

Secondary Outcomes (15)

• Part 2: Change From Baseline in Total Number of Errors on the GMLT

  Baseline, Day 2 at multiple time points post-scopolamine dose (up to 10 hours)

• Part 2: AUECt: GMLT Area Under the Effect Curve From Time 0 Hours to Time t (AUECt) (Net Area) for TAK-071

  Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose

• Part 2: Emax: GMLT Maximum Observed Effect (Emax) for TAK-071

  Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose

• Part 2: TEmax: Time to Reach GMLT Emax for TAK-071

  Day 2 pre-dose and at multiple timepoints (up to 10 hours) post-scopolamine dose

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

  Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1

Study Arms (11)

Part 1: TAK-071 80 mg + Scopolamine 0.5 mg

EXPERIMENTAL

TAK-071 80 milligram (mg), drug in capsule (DIC), orally, Day 1, followed by scopolamine 0.5 mg, injection, subcutaneously, Day 2. TAK-071 will be taken 24 hours before scopolamine injection.

Drug: Scopolamine; Drug: TAK-071

Part 2: Treatment Sequence ABDEC

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period1(A); followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(B);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(E);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(C). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence BCEAD

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(B);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(C);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(E);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period4(A);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(D). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence CDABE

EXPERIMENTAL

TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(C);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period3(A);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(B);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(E). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence DEBCA

EXPERIMENTAL

TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(E);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(B);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(C);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period5(A). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence EACDB

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(E);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period2(A);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(C);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(B). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence ACBED

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period1(A);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(C);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(B);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(E);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(D). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence BDCAE

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(B);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(D);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(C);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period4(A);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(E). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence CEDBA

EXPERIMENTAL

TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(C);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(E);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(B);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period5(A). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence DAECB

EXPERIMENTAL

TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(D);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period2(A);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period3(E);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(C); followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(B). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Part 2: Treatment Sequence EBADC

EXPERIMENTAL

TAK-071 placebo-matching DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period1(E);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period2(B);followed by TAK-071 placebo-matching DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection,SC,Day2 of Period3(A);followed by TAK-071 80mg, DIC, orally,Day1, donepezil 10mg, over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period4(D);followed by TAK-071 80mg, DIC, orally,Day1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5mg, injection,SC,Day2 of Period5(C). TAK-071 and donepezil will be taken 24 and 3 hours before scopolamine injection. A washout period of 3-weeks will be maintained between each treatment period.

Drug: Scopolamine; Drug: TAK-071; Drug: Donepezil; Drug: Scopolamine Placebo; Drug: TAK-071 Placebo; Drug: Donepezil Placebo

Interventions

Scopolamine DRUG

Scopolamine subcutaneous injection

Part 1: TAK-071 80 mg + Scopolamine 0.5 mg; Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

TAK-071 DRUG

TAK-071 DIC

Part 1: TAK-071 80 mg + Scopolamine 0.5 mg; Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

Donepezil DRUG

Donepezil over-encapsulated tablet

Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

Scopolamine Placebo DRUG

Scopolamine placebo-matching subcutaneous injection

Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

TAK-071 Placebo DRUG

TAK-071 placebo-matching DIC

Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

Donepezil Placebo DRUG

Donepezil placebo-matching over-encapsulated tablet

Part 2: Treatment Sequence ABDEC; Part 2: Treatment Sequence ACBED; Part 2: Treatment Sequence BCEAD; Part 2: Treatment Sequence BDCAE; Part 2: Treatment Sequence CDABE; Part 2: Treatment Sequence CEDBA; Part 2: Treatment Sequence DAECB; Part 2: Treatment Sequence DEBCA; Part 2: Treatment Sequence EACDB; Part 2: Treatment Sequence EBADC

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2), inclusive at Screening.
• Able to perform the CogState battery.
• Change from Baseline (average) in total GMLT errors of less than or equal to (\<=) -5 at 2 hours postdose of scopolamine.
• Sleepiness score less than (\<) 8 on the karolinska sleepiness scale (KSS) at 2 hours postdose of scopolamine.
• Passes a hearing test with at least 80 percent (%) correct responses and no more than 20% false positives. This test can be repeated once to determine eligibility.

You may not qualify if:

• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of 4 or more units per day) within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.
• Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1 of Period 1. Cotinine test is positive at Screening or Check-in (Day -1) of Period 1.
• Has poor peripheral venous access.
• Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1 of Period 1.
• Is a shift worker (night, late, or early resulting in irregular bed times) or has crossed or will cross more than 2 time zones within 48 hours in the period from 48 hours prior to Treatment Period 1, Day 1 until the end of Treatment Period 5.
• Reports symptoms suggesting evidence of a current sleep disorder or history of sleep disorder, including but not limited to sleep apnea, heavy snoring, primary or chronic insomnia, narcolepsy or restless leg syndrome, as judged by medical history.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Glendale, California, United States

Location

MeSH Terms

Interventions

Scopolamine; TAK-071; Donepezil

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Polycyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2016
• First Posted: September 28, 2016
• Study Start: November 21, 2016
• Primary Completion: August 2, 2017
• Study Completion: August 8, 2017
• Last Updated: June 14, 2019
• Results First Posted: June 14, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)