Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
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
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.
Interventions
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | Baseline (Day 1 of Confinement Period 1) and Day 2 post-AMPH dose in Confinement Period 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | Baseline (Day 1 of Confinement Period 1), and Day 1 post-TAK-041 and AMPH dose in Confinement Period 2 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in United Kingdom from 05 December 2016 to 23 August 2017.
Pre-assignment details
Healthy participants were enrolled in this study to receive TAK-041 in one of the 2 treatment groups: TAK-041 20 milligram (mg) or TAK-041 40 mg.
Participants by arm
| Arm | Count |
|---|---|
| TAK-041 20 mg \[11C\] 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 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. | 6 |
| TAK-041 40 mg \[11C\] 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. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | PET tracer synthesis failure | 1 | 0 |
| Overall Study | Study termination | 0 | 1 |
Baseline characteristics
| Characteristic | TAK-041 20 mg | TAK-041 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 10.98 | 46.2 years STANDARD_DEVIATION 8.16 | 39.7 years STANDARD_DEVIATION 11.45 |
| Alcohol Consumption of Less Than or Equal to (<=) 21 Units per Week | 5 Participants | 5 Participants | 10 Participants |
| Alcohol History Current drinker | 5 Participants | 5 Participants | 10 Participants |
| Alcohol History Never drunk | 1 Participants | 1 Participants | 2 Participants |
| Body Mass Index (BMI) | 26.65 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.814 | 27.88 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.375 | 27.26 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.662 |
| Caffeine History Had caffeine consumption | 4 Participants | 6 Participants | 10 Participants |
| Caffeine History Had no caffeine consumption | 2 Participants | 0 Participants | 2 Participants |
| Height | 179.0 centimeter (cm) STANDARD_DEVIATION 7.46 | 177.5 centimeter (cm) STANDARD_DEVIATION 7.12 | 178.3 centimeter (cm) STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
| Smoking History Current smoker | 0 Participants | 0 Participants | 0 Participants |
| Smoking History Ex-smoker | 2 Participants | 2 Participants | 4 Participants |
| Smoking History Never smoked | 4 Participants | 4 Participants | 8 Participants |
| Weight | 85.22 kilogram (kg) STANDARD_DEVIATION 4.585 | 87.90 kilogram (kg) STANDARD_DEVIATION 7.714 | 86.56 kilogram (kg) STANDARD_DEVIATION 6.21 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1 of Confinement Period 1) and Day 2 post-AMPH dose in Confinement Period 1
Population: The safety analysis set consisted of all participants who were enrolled and received a dose of study drug (\[11C\]PHNO, AMPH, or TAK-041) as part of this study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-041 20 mg | Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | Pu | 17 percentage of reduction | Standard Deviation 11 |
| TAK-041 20 mg | Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | VSt | 14 percentage of reduction | Standard Deviation 14 |
| TAK-041 40 mg | Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | Pu | 36 percentage of reduction | Standard Deviation 8 |
| TAK-041 40 mg | Change in Non-displaceable Binding Potential (BP-ND) in the TAK-041+AMPH Condition Compared to AMPH Alone | VSt | 23 percentage of reduction | Standard Deviation 20 |
Secondary
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.
Time frame: Baseline (Day 1 of Confinement Period 1), and Day 1 post-TAK-041 and AMPH dose in Confinement Period 2
Population: The safety analysis set consisted of all participants who were enrolled and received a dose of study drug (\[11C\]PHNO, AMPH, or TAK-041) as part of this study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-041 20 mg | Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | Pu | 17 percentage of reduction | Standard Deviation 11 |
| TAK-041 20 mg | Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | Vst | 14 percentage of reduction | Standard Deviation 14 |
| TAK-041 40 mg | Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | Pu | 36 percentage of reduction | Standard Deviation 8 |
| TAK-041 40 mg | Change in BP-ND in the TAK-041+AMPH Condition Compared to AMPH Alone as a Function of the Dose of TAK-041 Administered | Vst | 23 percentage of reduction | Standard Deviation 20 |