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

Phase 1

Terminated

• Conditions: Attention-Deficit/Hyperactivity Disorder
• Interventions: Drug: TAK-137; Drug: TAK-137 Placebo

• Registration Number: NCT02163915
• Lead Sponsor: Takeda

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-12
• Study First Submitted QC: 2014-06-12
• Study First Posted: 2014-06-16
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Results First Submitted: 2016-03-04
• Status Verified: 2016-06
• Results First Submitted QC: 2016-06-01
• Last Update Submitted: 2016-06-01
• Results First Posted: 2016-07-11
• Last Update Posted: 2016-07-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

1. Is a male or female adult who is 18 to 55 years of age, inclusive.
2. Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30.0 kg/m^2, inclusive at Screening.
3. Has a documented diagnosis of attention-deficit/hyperactivity disorder (ADHD) for a minimum of 1 year.
4. 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).

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Exclusion Criteria

1. Has received any investigational compound within 30 days prior to the first dose of study medication.
2. 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.
3. Has previously had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion.
4. 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).
5. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products.
6. 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.
7. 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: TAK-137 2 mg	TAK-137	TAK-137 2 mg, tablets, orally once on Days 1-7.
Cohort 3: TAK-137 5 mg	TAK-137	TAK-137 5 mg, tablets, orally once on Days 1-7.
Cohort 1: TAK-137 0.5 mg	TAK-137	TAK-137 0.5 mg, tablets, orally once on Days 1-7.
Cohort 4: TAK-137 10 mg	TAK-137	TAK-137 10 mg, tablets, orally once on Days 1-7.
Cohort 5: TAK-137 TBD	TAK-137	TAK-137, tablets, orally once on Days 1-7. Dose to be determined from data collected in Cohorts 1-3.
Cohorts 1-5: Placebo	TAK-137 Placebo	TAK-137 placebo-matching tablets, orally, once on Days 1-7.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	Day 1 up to Day 14	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.
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

Name	Time	Method
AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-137	Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose	Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.
Cmax: Maximum Observed Plasma Concentration for TAK-137	Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-137	Day 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose	Maximum observed steady-state plasma concentration during a dosing interval.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137	Days 1 and 7 pre-dose and at multiple timepoints (up to 24 hours) post-dose	Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.