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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1152-6846 | Other Identifier | World Health Organization |
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To allow evaluation of emerging non-clinical data (see detailed description below)
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The purpose of this study is to characterize the safety and tolerability of TAK-137 when administered as multiple oral doses in adults with attention-deficit/hyperactivity disorder (ADHD).
The drug being tested in this study is called TAK-137. TAK-137 is being tested to find a safe and well-tolerated dose and to assess how TAK-137 is metabolized in people with attention-deficit/ hyperactivity disorder (ADHD). This study will look at side effects and lab results in people who take TAK-137. This study is designed as a randomized, sequential-cohort, multiple rising dose study.
Therefore, the TAK-137 2 mg Cohort will not start until the TAK-137 0.5 mg Cohort has completed, etc.
This trial will be conducted in the United States. The overall time to participate in this study is up to 42 days. Participants will make at least 2 visits to the clinic, including one 9-day period of confinement to the clinic. All participants will be contacted by telephone 7 days after the last dose of study drug for a follow-up assessment.
A decision was made to terminate this study so that emerging data from preclinical studies could be further assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: TAK-137 0.5 mg | Experimental | TAK-137 0.5 mg, tablets, orally once on Days 1-7. |
|
| Cohort 2: TAK-137 2 mg | Experimental | TAK-137 2 mg, tablets, orally once on Days 1-7. |
|
| Cohort 3: TAK-137 5 mg | Experimental | TAK-137 5 mg, tablets, orally once on Days 1-7. |
|
| Cohort 4: TAK-137 10 mg | Experimental | TAK-137 10 mg, tablets, orally once on Days 1-7. |
|
| Cohort 5: TAK-137 TBD | Experimental | TAK-137, tablets, orally once on Days 1-7. Dose to be determined from data collected in Cohorts 1-3. |
|
| Cohorts 1-5: Placebo | Experimental | TAK-137 placebo-matching tablets, orally, once on Days 1-7. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-137 | Drug | TAK-137 tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Day 1 up to Day 14 |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Day 1 up to Day 8 | |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Day 1 up to Day 8 | |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | Day 1 up to Day 8 | |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | Day 1 up to Day 8 | |
| Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Day 1 up to Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-137 | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
| Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Marlton | New York | 08053 | United States |
Participants with a historical diagnosis of attention-deficit/hyperactivity disorder (ADHD) were enrolled in one of the five cohorts to receive TAK-137 (0.5 milligram [mg], 2 mg, 5 mg, 10 mg, or matching placebo) once daily for up to 7 days.
Participants took part in the study at 1 investigative site in the United States from 23 May 2014 to 03 November 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohorts 1-4: Placebo | TAK-137 placebo-matching tablets, orally, once on Days 1-7 under fasting conditions. |
| FG001 | Cohort 1: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| FG002 | Cohort 2: TAK-137 2 mg | TAK-137 2 mg, tablets, orally once on Days 1-7 under fasting condition. |
| FG003 | Cohort 3: TAK-137 5 mg | TAK-137 5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| FG004 | Cohort 4: TAK-137 10 mg | TAK-137 10 mg, tablets, orally once on Days 1-7 under fasting condition. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis set was defined as all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohorts 1-4: Placebo | TAK-137 placebo-matching tablets, orally, once on Days 1-7 under fasting conditions. |
| BG001 | Cohort 1: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 14 |
|
Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug (Day 7).
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 | Cohorts 1-4: Placebo | TAK-137 placebo-matching tablets, orally, once on Days 1-7 under fasting conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000705611 | TAK-137 |
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|
| TAK-137 Placebo | Drug | TAK-137 placebo-matching tablets |
|
Maximum observed steady-state plasma concentration during a dosing interval. |
| Day 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
| AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval. | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
| Study termination |
|
| Physician Decision |
|
| BG002 | Cohort 2: TAK-137 2 mg | TAK-137 2 mg, tablets, orally once on Days 1-7 under fasting condition. |
| BG003 | Cohort 3: TAK-137 5 mg | TAK-137 5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| BG004 | Cohort 4: TAK-137 10 mg | TAK-137 10 mg, tablets, orally once on Days 1-7 under fasting condition. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Body Mass Index | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
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| Caffeine Consumption | Number | participants |
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| Smoking Status | The baseline characteristic was categorized as never smoked, current smoker and ex-smoker. There were no participants available under current smoker. | Number | participants |
|
| Alcohol consumption | Number | participants |
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| Female Reproductive Status | The baseline measure was categorized as Surgically sterile: permanent method of contraception; Female of childbearing potential; and Not applicable: participant was male. | Number | participants |
|
| ADHD Category | As per national institute of mental health (NIMH) ADHA was categorized as Combined: participants who had greater than equal to (>=) 6 symptoms of inattention and hyperactivity-impulsivity; Hyperactive/impulsive: participants who had >=6 symptoms of hyperactivity-impulsivity and less than (<) 6 symptoms of inattention; and Inattentive; participants who had >=6 symptoms of inattention and <6 symptoms of hyperactivity-impulsivity. There were no participants available under hyperactive/impulsive. | Number | participants |
|
| OG001 | Cohort 1: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| OG002 | Cohort 2: TAK-137 2 mg | TAK-137 2 mg, tablets, orally once on Days 1-7 under fasting condition. |
| OG003 | Cohort 3: TAK-137 5 mg | TAK-137 5 mg, tablets, orally once on Days 1-7 under fasting condition. |
| OG004 | Cohort 4: TAK-137 10 mg | TAK-137 10 mg, tablets, orally once on Days 1-7 under fasting condition. |
|
|
| Primary | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 8 |
|
|
|
| Primary | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Pulse Measurements at Least Once Post Dose | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 8 |
|
|
|
| Primary | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Blood Pressure Measurements at Least Once Post Dose | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 8 |
|
|
|
| Primary | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Heart Rate Measurements at Least Once Post Dose | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 8 |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK-137 | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
|
|
|
| Secondary | Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137 | Maximum observed steady-state plasma concentration during a dosing interval. | Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration. | Posted | Mean | Standard Deviation | ng/mL | Day 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration. | Posted | Median | Full Range | hours | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
|
|
|
| Secondary | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137 | Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval. | Pharmacokinetic analysis set was defined as all participants who received at least one dose of study drug and had at least one measurable plasma concentration. | Posted | Mean | Standard Deviation | nanogram hours per milliliter (ng*hr/mL) | Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
|
|
|
| Primary | Percentage of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Day 1 up to Day 8 |
|
|
|
| 0 |
| 10 |
| 5 |
| 10 |
| EG001 | Cohort 1: TAK-137 0.5 mg | TAK-137 0.5 mg, tablets, orally once on Days 1-7 under fasting condition. | 0 | 8 | 5 | 8 |
| EG002 | Cohort 2: TAK-137 2 mg | TAK-137 2 mg, tablets, orally once on Days 1-7 under fasting condition. | 0 | 10 | 0 | 10 |
| EG003 | Cohort 3: TAK-137 5 mg | TAK-137 5 mg, tablets, orally once on Days 1-7 under fasting condition. | 0 | 9 | 6 | 9 |
| EG004 | Cohort 4: TAK-137 10 mg | TAK-137 10 mg, tablets, orally once on Days 1-7 under fasting condition. | 0 | 10 | 2 | 10 |
| Electroencephalogram abnormal | Investigations | MedDRA (17.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Infusion site haematoma | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Heart rate decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
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| Blood pressure diastolic decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (17.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
|
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.
| Standing, After 1 Minute: < 50 bpm |
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| Standing, After 1 Minute: > 120 bpm |
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| Standing, After 3 Minutes: < 50 bpm |
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| Standing, After 3 Minutes: > 120 bpm |
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| SBP: Standing, After 3 Minutes: <85 mmHg |
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| DBP: Supine, After 5 Minutes: <50 mmHg |
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| DBP: Standing, After 1 Minute: <50 mmHg |
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| DBP: Standing, After 1 Minute: >110 mmHg |
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| DBP: Standing, After 3 Minutes: <50 mmHg |
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| DBP: Standing, After 3 Minutes: >110 mmHg |
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| Day 7 (n= 8, 8, 6, 6) |
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| Day 7 (n= 8, 8, 6, 4) |
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| PR Interval: ≥200 msec |
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| QRS Interval: ≤80 msec |
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| QT Interval: ≥460 msec |
|