Healthy Volunteers
Conditions
Keywords
Drug Therapy
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).
Detailed description
The drug being tested in this study is called TAK-071. This study will look at the effect of a single oral dose of TAK-071, a novel muscarinic acetylcholine receptor 1 positive allosteric modulator, on scopolamine-induced deficits in cognitive function in healthy adult male participants. The study consists of two parts: Part 1 is a substudy to explore PK profile of TAK-071 in the presence of light meal and coadministration of scopolamine to determine TAK-071 dose for the next part; Part 2 is the main the study to assess the effects of TAK-071 on scopolamine-induced cognitive impairment. The study will enroll approximately 6 participants in Part 1 and 40 participants in Part 2. Participant will be assigned to received TAK-071 along with scopolamine in Part 1 and will be randomly assigned to one of the ten treatment sequences in Part 2-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need): Part 2: Treatment Sequence ABDEC Part 2: Treatment Sequence BCEAD Part 2: Treatment Sequence CDABE Part 2: Treatment Sequence DEBCA Part 2: Treatment Sequence EACDB Part 2: Treatment Sequence ACBED Part 2: Treatment Sequence BDCAE Part 2: Treatment Sequence CEDBA Part 2: Treatment Sequence DAECB Part 2: Treatment Sequence EBADC Where A=scopolamine matching placebo SC + TAK-071 matching placebo oral (PO) + donepezil matching placebo PO; B=scopolamine 0.5 mg SC + TAK-071 matching placebo PO + donepezil matching placebo PO; C=scopolamine 0.5 mg SC + TAK-071 PO + donepezil matching placebo PO; D=scopolamine 0.5 mg SC + TAK-071 PO + donepezil 10 mg PO; and E=scopolamine 0.5 mg SC + TAK-071 matching placebo PO + donepezil 10 mg PO. The dose of TAK-071 that was well-tolerated in the TAK-071-1001 study (NCT02769065) will be selected, based on the safety and tolerability data from the single-rising dose (SRD) study for administration in Part 1. Each participant will also receive scopolamine 0.5 mg, injection, SC, once at the time of Screening. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 5.7 weeks in Part 1 and 21 weeks in Part 2. Participants will remain confined to the clinic for 4 days during Part 1 and 3 days during the each intervention period in Part 2. Participants will be contacted by telephone on Day 12 in Part 1 and Day 9 of Period 5 in Part 2 for a follow-up assessment.
Interventions
DRUGScopolamine
Scopolamine subcutaneous injection
DRUGTAK-071
TAK-071 DIC
DRUGDonepezil
Donepezil over-encapsulated tablet
Scopolamine placebo-matching subcutaneous injection
DRUGTAK-071 Placebo
TAK-071 placebo-matching DIC
Donepezil placebo-matching over-encapsulated tablet
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. 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. Additional inclusion criteria for Part 2: 1. Able to perform the CogState battery. 2. Change from Baseline (average) in total GMLT errors of less than or equal to (\<=) -5 at 2 hours postdose of scopolamine. 3. Sleepiness score less than (\<) 8 on the karolinska sleepiness scale (KSS) at 2 hours postdose of scopolamine. 4. 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.
Exclusion criteria
1. 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. 2. 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. 3. Has poor peripheral venous access. 4. 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. 5. 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. 6. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1 |
| 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) |
| Tmax: Time to Reach the Maximum Observed Plasma Concentration(Cmax) for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
| AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 24 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 24 hours) post-scopolamine dose |
| AUCt1-t2: Area Under the Plasma Concentration-Time Curve From Time t1 to Time t2 for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
| AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
| T1/2z: Terminal Disposition Phase Elimination Half-Life in Plasma for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-071 | Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United states from 21 November 2016 to 08 August 2017.
Pre-assignment details
Healthy male participants were enrolled in this 2-part study to receive: TAK-071, scopolamine in Part 1; TAK-071, scopolamine and donepezil in a cross-over sequence in Part 2. The study was terminated prior to start of Part 2 intervention period 2 due to indication change.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: TAK-071 80 mg + Scopolamine 0.5 mg TAK-071 80 mg, DIC, orally, on Day 1, followed by scopolamine 0.5 mg, injection, SC, on Day 2. TAK-071 will be taken 24 hours before scopolamine injection. | 6 |
| Part 2: Treatment Sequence ABDEC TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 1 (A); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (B); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (E); followed by TAK-071, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (C). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence BCEAD TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (B); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (C); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (E); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 4 (A); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (D). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence CDABE TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (C); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 3 (A); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (B); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (E). A washout period of 3-weeks was maintained between each treatment period | 1 |
| Part 2: Treatment Sequence DEBCA TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (E); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (B); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (C); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 5 (A). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence EACDB TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (E); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 2 (A);followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (C); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (B). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence ACBED TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 1 (A); followed by TAK-071 DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (C); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (B); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (E); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (D). A washout period of 3-weeks was maintained between each treatment period. | 2 |
| Part 2: Treatment Sequence BDCAE TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (B);followed by TAK-071 80 mg, DIC, orally, Day1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (D);followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (C);followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 4 (A); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (E). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence CEDBA TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (C); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (E); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, Day 2 of Period 4 (B); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 5 (A). A washout period of 3-weeks was maintained between each treatment period. | 2 |
| Part 2: Treatment Sequence DAECB TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (D); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 2 (A); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 3 (E); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (C); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (B). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Part 2: Treatment Sequence EBADC TAK-071 80 mg, placebo-matching DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 1 (E); followed by TAK-071 placebo-matching DIC, orally, Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 2 (B); followed by TAK-071 placebo-matching DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine placebo-matching injection, SC, on Day 2 of Period 3 (A); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil 10 mg, over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 4 (D); followed by TAK-071 80 mg, DIC, orally, on Day 1, donepezil placebo-matching over-encapsulated tablet, orally along with scopolamine 0.5 mg, injection, SC, on Day 2 of Period 5 (C). A washout period of 3-weeks was maintained between each treatment period. | 1 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 2: Intervention Period 1 (2 Days) | Study termination | 0 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Part 2: Treatment Sequence EBADC | Part 1: TAK-071 80 mg + Scopolamine 0.5 mg | Part 2: Treatment Sequence ABDEC | Part 2: Treatment Sequence BCEAD | Part 2: Treatment Sequence CDABE | Part 2: Treatment Sequence DEBCA | Part 2: Treatment Sequence EACDB | Part 2: Treatment Sequence ACBED | Part 2: Treatment Sequence BDCAE | Part 2: Treatment Sequence CEDBA | Part 2: Treatment Sequence DAECB | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Academic Qualifications Elementary school | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Academic Qualifications High school | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Academic Qualifications No degree or diploma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Academic Qualifications Non university degree | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Academic Qualifications University | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 11 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 18 Participants |
| Alcohol Classification Current drinker: had 4 or more units per day | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Alcohol Classification Current drinker: had less than (<) 4 units per day | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
| Alcohol Classification Ex-drinker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Alcohol Classification Never drunk | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 10 Participants |
| Caffeine Consumption Had caffeine consumption | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Caffeine Consumption Had no caffeine consumption | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 10 Participants |
| Region of Enrollment United States | 1 participants | 6 participants | 1 participants | 1 participants | 1 participants | 1 participants | 1 participants | 2 participants | 1 participants | 2 participants | 1 participants | 18 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 18 Participants |
| Smoking Classification Current smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Classification Ex-smoker | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Smoking Classification Never smoked | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 2 | 0 / 3 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 4 / 6 | 2 / 3 | 2 / 2 | 3 / 3 | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 2 | 0 / 3 | 0 / 2 | 0 / 2 |
Outcome results
Primary
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
Time frame: Baseline, 2 hours post scopolamine dose on Day 2
Population: No data was collected for Part 2 due to premature study termination because of indication change.
Secondary
AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 24 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 24 hours) post-scopolamine dose
Population: The PK set included all participants who received study drug and had at least 1 measurable plasma concentration. No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Treatment A | AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for TAK-071 | 19330 h*ng/mL | Geometric Coefficient of Variation 16 |
Secondary
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: The PK set included all participants who received study drug and had at least 1 measurable plasma concentration. No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Treatment A | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071 | 94100 h*ng/mL | Geometric Coefficient of Variation 26.8 |
Secondary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: The PK set included all participants who received study drug and had at least 1 measurable plasma concentration.No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Treatment A | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-071 | 82010 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25 |
Secondary
AUCt1-t2: Area Under the Plasma Concentration-Time Curve From Time t1 to Time t2 for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: As per change in planned analyses, data was not collected.
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: The pharmacokinetic (PK) set included all participants who received study drug and had at least 1 measurable plasma concentration. No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Treatment A | Cmax: Maximum Observed Plasma Concentration for TAK-071 | 1066 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16.8 |
Secondary
Part 2: AUECt: GMLT Area Under the Effect Curve From Time 0 Hours to Time t (AUECt) (Net Area) for TAK-071
Time frame: Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: No data was collected for Part 2 due to premature study termination because of indication change.
Secondary
Part 2: Change From Baseline in Total Number of Errors on the GMLT
Time frame: Baseline, Day 2 at multiple time points post-scopolamine dose (up to 10 hours)
Population: No data was collected for Part 2 due to premature study termination because of indication change.
Secondary
Part 2: Emax: GMLT Maximum Observed Effect (Emax) for TAK-071
Time frame: Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: No data was collected for Part 2 due to premature study termination because of indication change.
Secondary
Part 2: TEmax: Time to Reach GMLT Emax for TAK-071
Time frame: Day 2 pre-dose and at multiple timepoints (up to 10 hours) post-scopolamine dose
Population: No data was collected for Part 2 due to premature study termination because of indication change.
Secondary
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
Population: The safety analysis set included all participants who were enrolled and received 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Treatment A | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 100.0 percentage of participants |
Secondary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose
Time frame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
Population: The safety analysis set included all participants who were enrolled and received 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose | 0 percentage of participants |
Secondary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose
Time frame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
Population: The safety analysis set included all participants who were enrolled and received 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 16.7 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 50.0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose | 50.0 percentage of participants |
Secondary
Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose
Time frame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
Population: The safety analysis set included all participants who were enrolled and received 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 0 percentage of participants |
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 33.3 percentage of participants |
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment A | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 16.7 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 0 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 0 percentage of participants |
| Part 2: Treatment B | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 33.3 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 0 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 0 percentage of participants |
| Part 2: Treatment C | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 50.0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 0 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 33.3 percentage of participants |
| Part 2: Treatment D | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Diastolic Blood Pressure (mmHg)/Supine <50 mmHg | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: <35.6 Celsius | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Temperature: >37.7 Celsius | 0 percentage of participants |
| Part 2: Treatment E | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Pulse rate/supine: <50 beats per minute | 50.0 percentage of participants |
Secondary
T1/2z: Terminal Disposition Phase Elimination Half-Life in Plasma for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: The PK set included all participants who received study drug and had at least 1 measurable plasma concentration. No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 2: Treatment A | T1/2z: Terminal Disposition Phase Elimination Half-Life in Plasma for TAK-071 | 47.02 hours | Standard Deviation 14.864 |
Secondary
Tmax: Time to Reach the Maximum Observed Plasma Concentration(Cmax) for TAK-071
Time frame: Part 1: Day 1 pre-TAK-071 dose and at multiple time points (up to 168 hours) post-TAK-071 dose; Part 2: Day 2 pre-TAK-071 dose and at multiple time points (up to 10 hours) post-scopolamine dose
Population: The PK set included all participants who received study drug and had at least 1 measurable plasma concentration. No data was collected for Part 2 due to premature study termination because of indication change.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2: Treatment A | Tmax: Time to Reach the Maximum Observed Plasma Concentration(Cmax) for TAK-071 | 30.00 hours |