Clinical trial NCT02918266: TAK-071 Scopolamine-Induced Cognitive Impairment Study
Official title: A Randomized, Double-Blind, Sponsor Unblinded, Placebo-Controlled, 5-Period Crossover, Phase 1b Study To Evaluate The Effects Of Single Oral Administration of TAK-071 On Scopolamine-Induced Cognitive Impairment In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-09-28
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline, 2 hours post scopolamine dose on Day 2
Secondary outcomes:
measure: Part 2: Change From Baseline in Total Number of Errors on the GMLT
timeFrame: Baseline, Day 2 at multiple time points post-scopolamine dose (up to 10 hours)
measure: Part 2: AUECt: GMLT Area Under the Effect Curve From Time 0 Hours to Time t (AUECt) (Net Area) for TAK-071
timeFrame: Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose
measure: Part 2: Emax: GMLT Maximum Observed Effect (Emax) for TAK-071
timeFrame: Day 2 pre-dose and at multiple time points (up to 10 hours) post-scopolamine dose
measure: Part 2: TEmax: Time to Reach GMLT Emax for TAK-071
timeFrame: Day 2 pre-dose and at multiple timepoints (up to 10 hours) post-scopolamine dose
measure: Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
timeFrame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
measure: Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Postdose
timeFrame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
measure: Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose
timeFrame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
measure: Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Electrocardiogram (ECG) at Least Once Postdose
timeFrame: Part 1: Baseline up to Day 12; Part 2: Baseline up to Day 9 of Period 1
measure: Cmax: Maximum Observed Plasma Concentration for TAK-071
timeFrame: 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
measure: Tmax: Time to Reach the Maximum Observed Plasma Concentration(Cmax) for TAK-071
timeFrame: 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
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-071
timeFrame: 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
measure: AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for TAK-071
timeFrame: 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
measure: AUCt1-t2: Area Under the Plasma Concentration-Time Curve From Time t1 to Time t2 for TAK-071
timeFrame: 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
measure: AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-071
timeFrame: 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
measure: T1/2z: Terminal Disposition Phase Elimination Half-Life in Plasma for TAK-071
timeFrame: 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
Other outcomes:
Locations:
city: Glendale
country: United States
state: California
Study officials:
References: