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

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

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).

Study Overview

• Status: Terminated
• Conditions: Attention-Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: TAK-137; Drug: TAK-137 Placebo

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 Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Marlton, New York, United States, 08053

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 12, 2014
• First Posted (Estimate): June 16, 2014

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: June 1, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: TAK-137_102; U1111-1152-6846 (Other Identifier: World Health Organization)