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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1184-1947 | Registry Identifier | WHO | |
| 2016-002346-23 | EudraCT Number |
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| Name | Class |
|---|---|
| Takeda | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-041 20 mg | Experimental | [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. |
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| TAK-041 40 mg | Experimental | [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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amphetamine | Drug | Amphetamine tablets. |
| |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Medicines Research | London | NW107EW | United Kingdom |
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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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 took part in the study at 1 investigative site in United Kingdom from 05 December 2016 to 23 August 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 27, 2019 | Dec 5, 2019 |
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| TAK -041 |
| Drug |
TAK-041 oral suspension. |
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| [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) | Drug | [11C]PHNO injection. |
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| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | centimeter (cm) |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
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| Smoking History | Count of Participants | Participants |
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| Alcohol History | Count of Participants | Participants |
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| Alcohol Consumption of Less Than or Equal to (<=) 21 Units per Week | Alcohol consumption was assessed in the participants who were current alcohol drinker. | Count of Participants | Participants |
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| Caffeine History | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | percentage of reduction | Baseline (Day 1 of Confinement Period 1) and Day 2 post-AMPH dose in Confinement Period 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | percentage of reduction | Baseline (Day 1 of Confinement Period 1), and Day 1 post-TAK-041 and AMPH dose in Confinement Period 2 |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG001 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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| Herpes Zoster | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Feb 21, 2017 | Dec 5, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D000661 | Amphetamine |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Had no caffeine consumption |
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