A Single-Dose Positron Emission Tomography (PET) Study to Determine the Effect of TAK-041 on Amphetamine-Induced Dopamine Release in the Central Nervous System (CNS)

Study Overview
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Brief Summary
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The purpose of this study is to determine brain penetration of single oral doses of TAK-041 and its effects on amphetamine-induced dopamine release in the Central Nervous System (CNS).

Detailed Description
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The drug being tested in this study is called TAK-041. This study will look at brain penetration of single oral doses of TAK-041 and its effects on amphetamine-induced dopamine release in the CNS. The study will enroll participants until 12 evaluable participants complete all study procedures. The first 4 participants enrolled in this study will receive a dose of 20 mg TAK-041 and 0.50 milligram per kilogram (mg/kg) dose of amphetamine. The dose for subsequent participants will be determined based on the results of amphetamine-induced dopamine release in the first 4 participants (5 to 40 for TAK-041 and 0.25 or 0.50 mg/kg for the amphetamine). This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is approximately 92 days. Participants will remain confined to the clinic for 3 to 4 days during 2 confinement periods. Participants will make monthly visits during Days 8-64 and a final visit 30 days later.

Official Title
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A Phase 1, Open-Label, Positron Emission Tomography Study in Healthy Subjects to Determine the Effect of TAK-041 on Amphetamine-Induced Dopamine Release in the CNS After Single-Dose Oral Administration

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Amphetamine
* Drug: TAK -041
* Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is in good health as determined by physical examination, electrocardiogram (ECG), and laboratory evaluations. Weighs at least 45 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. Exclusion Criteria: Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of more than 21 units per week) 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 8 grams of pure alcohol, which is equivalent to 10 milliliter (mL) of pure ethanol (alcohol) or approximately a half-pint of beer, 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 on Day -1. Cotinine test is positive at Screening or Check-in (Day -1). Has poor peripheral venous access. Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Confinement Period 1. Has had previous research-related exposure to ionizing radiation such that, in combination with the exposure from this study, their exposure will be greater than (>)10 millisievert (mSv) for the previous year. Has a contraindication to magnetic resonance imaging (MRI) based on the standard MRI screening questionnaire. Contraindications include ferromagnetic foreign bodies (example, shrapnel, ferromagnetic fragments in the orbital area), certain implanted medical devices (example, aneurysm clips, cardiac pacemakers), or claustrophobia. Has findings on the screening brain MRI scan that will potentially compromise participant safety or the scientific integrity of the study data if the participant were to participate in this study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-041 20 mg<br>[11C] PHNO 180 megabecquerel (MBq), injection, intravenously, prior to positron emission tomography (PET) scan on Day 1, followed by amphetamine (AMPH) 0.5 milligram per kilogram (mg/kg), tablet, orally, once and [11C] PHNO 180 MBq, injection, intravenously, prior to PET scan post-AMPH dose on Day 2 of Confinement Period 1, followed by a 5 to 45 days of interval period, further followed by TAK-041 20 mg, suspension, orally, once, followed by AMPH 0.5 mg, tablet, orally, once and [11C] PHNO 180 MBq, injection, intravenously, prior to PET scan post-AMPH dose on Day 1 of Confinement Period 2. | Drug: Amphetamine<br>* Amphetamine tablets.<br>Drug: TAK -041<br>* TAK-041 oral suspension.<br>Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)<br>* [11C]PHNO injection.<br>|
| Experimental: TAK-041 40 mg<br>[11C] PHNO 180 MBq, injection, intravenously, prior to PET scan on Day 1, followed by AMPH 0.5 mg/kg, tablet, orally, once and [11C] PHNO 180 MBq, injection, intravenously, prior to PET scan post-AMPH dose on Day 2 of Confinement Period 1, followed by a 5 to 45 days of interval period, further followed by TAK-041 40 mg, suspension, orally, once, followed by AMPH 0.5 mg, tablet, orally, once and [11C] PHNO 180 MBq, injection, intravenously, prior to PET scan post-AMPH dose on Day 1 of Confinement Period 2. | Drug: Amphetamine<br>* Amphetamine tablets.<br>Drug: TAK -041<br>* TAK-041 oral suspension.<br>Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)<br>* [11C]PHNO injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | The AMPH-induced change in binding potential relative to the non-displaceable component in the basal ganglia (putamen [Pu], ventral striatum [VSt]) which was the region of interest (ROI) was calculated as the percentage of reduction in specific binding from Baseline to postdose following AMPH. | Baseline (Day 1 of Confinement Period 1) and Day 2 post-AMPH dose in Confinement Period 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | The effect of predosing with TAK-041 on the AMPH challenge was calculated as the relative change in the percentage reduction in specific binding in ROI in the AMPH+TAK-041 condition compared to AMPH alone. | Baseline (Day 1 of Confinement Period 1), and Day 1 post-TAK-041 and AMPH dose in Confinement Period 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy