Trial Outcomes & Findings for 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) (NCT NCT02959892)

Last Updated: 2021-03-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Baseline (Day 1 of Confinement Period 1) and Day 2 post-AMPH dose in Confinement Period 1

Results posted on

2021-03-19

Participant Flow

Participants took part in the study at 1 investigative site in United Kingdom from 05 December 2016 to 23 August 2017.

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.

Participant milestones

Participant milestones
Measure	TAK-041 20 mg \[11C\] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (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.	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.
Overall Study STARTED	6	6
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TAK-041 20 mg \[11C\] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (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.	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.
Overall Study PET tracer synthesis failure	1	0
Overall Study Study termination	0	1

Baseline Characteristics

Alcohol consumption was assessed in the participants who were current alcohol drinker.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAK-041 20 mg n=6 Participants \[11C\] 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.	TAK-041 40 mg n=6 Participants \[11C\] 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.
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	36 percentage of reduction Standard Deviation 8
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	23 percentage of reduction Standard Deviation 20

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	TAK-041 20 mg n=6 Participants \[11C\] 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.	TAK-041 40 mg n=6 Participants \[11C\] 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.
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	36 percentage of reduction Standard Deviation 8
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	23 percentage of reduction Standard Deviation 20

Adverse Events

TAK-041 20 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

TAK-041 40 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	TAK-041 20 mg n=6 participants at risk \[11C\] 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.	TAK-041 40 mg n=6 participants at risk \[11C\] 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.
Infections and infestations Pharyngitis	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 92 days after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 92 days after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Herpes Zoster	0.00% 0/6 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 92 days after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 92 days after the last dose of study drug At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Publication restrictions are in place

Restriction type: OTHER

Measure	TAK-041 20 mg n=6 Participants \[11C\] 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.	TAK-041 40 mg n=6 Participants \[11C\] 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.	Total n=12 Participants Total of all reporting groups
Age, Continuous	33.2 years STANDARD_DEVIATION 10.98 • n=6 Participants	46.2 years STANDARD_DEVIATION 8.16 • n=6 Participants	39.7 years STANDARD_DEVIATION 11.45 • n=12 Participants
Sex: Female, Male Female	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Sex: Female, Male Male	6 Participants n=6 Participants	6 Participants n=6 Participants	12 Participants n=12 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Black or African American	2 Participants n=6 Participants	1 Participants n=6 Participants	3 Participants n=12 Participants
Race (NIH/OMB) White	4 Participants n=6 Participants	5 Participants n=6 Participants	9 Participants n=12 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Height	179.0 centimeter (cm) STANDARD_DEVIATION 7.46 • n=6 Participants	177.5 centimeter (cm) STANDARD_DEVIATION 7.12 • n=6 Participants	178.3 centimeter (cm) STANDARD_DEVIATION 7.00 • n=12 Participants
Weight	85.22 kilogram (kg) STANDARD_DEVIATION 4.585 • n=6 Participants	87.90 kilogram (kg) STANDARD_DEVIATION 7.714 • n=6 Participants	86.56 kilogram (kg) STANDARD_DEVIATION 6.210 • n=12 Participants
Body Mass Index (BMI)	26.65 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.814 • n=6 Participants	27.88 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.375 • n=6 Participants	27.26 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.662 • n=12 Participants
Smoking History Never smoked	4 Participants n=6 Participants	4 Participants n=6 Participants	8 Participants n=12 Participants
Smoking History Current smoker	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Smoking History Ex-smoker	2 Participants n=6 Participants	2 Participants n=6 Participants	4 Participants n=12 Participants
Alcohol History Never drunk	1 Participants n=6 Participants	1 Participants n=6 Participants	2 Participants n=12 Participants
Alcohol History Current drinker	5 Participants n=6 Participants	5 Participants n=6 Participants	10 Participants n=12 Participants
Alcohol Consumption of Less Than or Equal to (<=) 21 Units per Week	5 Participants n=5 Participants • Alcohol consumption was assessed in the participants who were current alcohol drinker.	5 Participants n=5 Participants • Alcohol consumption was assessed in the participants who were current alcohol drinker.	10 Participants n=10 Participants • Alcohol consumption was assessed in the participants who were current alcohol drinker.
Caffeine History Had caffeine consumption	4 Participants n=6 Participants	6 Participants n=6 Participants	10 Participants n=12 Participants
Caffeine History Had no caffeine consumption	2 Participants n=6 Participants	0 Participants n=6 Participants	2 Participants n=12 Participants