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)

Neurocrine Biosciences

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Amphetamine; Drug: TAK -041; Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02959892

U1111-1184-1947 (Registry Identifier)

TAK-041-1002

2016-002346-23 (EudraCT Number)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 12 patients

Sex: Male

Ages: 20 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Is in good health as determined by physical examination, electrocardiogram (ECG), and laboratory evaluations.
2. 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

1. 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.
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 on Day -1. Cotinine test is positive at Screening or Check-in (Day -1).
3. Has poor peripheral venous access.
4. 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.
5. 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.
6. 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.
7. 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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

TAK-041 20 mg

Experimental group

Description:

\[11C\] 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.

Treatment:

Drug: Amphetamine

Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Drug: TAK -041

TAK-041 40 mg

Experimental group

Description:

\[11C\] 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.

Treatment:

Drug: Amphetamine

Drug: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Drug: TAK -041