Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of TAK-137 in Adults With Attention-Deficit/Hyperactivity Disorder.

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Multiple Rising Doses of TAK-137 in Adult Subjects With Attention-Deficit/Hyperactivity Disorder

Conditions
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Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: TAK-137
* Drug: TAK-137 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a male or female adult who is 18 to 55 years of age, inclusive. Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30.0 kg/m^2, inclusive at Screening. Has a documented diagnosis of attention-deficit/hyperactivity disorder (ADHD) for a minimum of 1 year. Is willing to discontinue all medications to treat adult ADHD (eg, stimulants, antidepressants) and all other medications and dietary products as specified in the protocol, from Day -7 until Follow-up phone call (Day 14). Exclusion Criteria: Has received any investigational compound within 30 days prior to the first dose of study medication. Has uncontrolled, clinically significant neurologic (including mildly abnormal or significantly abnormal EEG at screening), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder (other than ADHD), or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. Has previously had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion. Has a positive urine drug result for drugs of abuse other than amphetamines or other medications to treat ADHD or positive result for alcohol at Screening or Check-in (Day -1). Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products. Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period. 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 (Day -1).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TAK-137 0.5 mg<br>TAK-137 0.5 mg, tablets, orally once on Days 1-7. | Drug: TAK-137<br>* TAK-137 tablets<br>|
| Experimental: Cohort 2: TAK-137 2 mg<br>TAK-137 2 mg, tablets, orally once on Days 1-7. | Drug: TAK-137<br>* TAK-137 tablets<br>|
| Experimental: Cohort 3: TAK-137 5 mg<br>TAK-137 5 mg, tablets, orally once on Days 1-7. | Drug: TAK-137<br>* TAK-137 tablets<br>|
| Experimental: Cohort 4: TAK-137 10 mg<br>TAK-137 10 mg, tablets, orally once on Days 1-7. | Drug: TAK-137<br>* TAK-137 tablets<br>|
| Experimental: Cohort 5: TAK-137 TBD<br>TAK-137, tablets, orally once on Days 1-7. Dose to be determined from data collected in Cohorts 1-3. | Drug: TAK-137<br>* TAK-137 tablets<br>|
| Experimental: Cohorts 1-5: Placebo<br>TAK-137 placebo-matching tablets, orally, once on Days 1-7. | Drug: TAK-137 Placebo<br>* TAK-137 placebo-matching tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy