Clinical trial NCT02334982: Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of TAK-137 in Healthy Participants
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Escalating Single Doses of TAK-137 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dose Finding Study
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-01-09
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to characterize the safety and tolerability profile of TAK-137 when administered as a single dose of tablets at escalating dose levels in healthy participants.

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. This study looked at safety (lab results and side effects) and pharmacokinetic properties (drug absorption, distribution, metabolism, and excretion) in people who took TAK-137. This study was designed as a single ascending 6 Cohort dose study with planned doses of 2, 5, 15, 50, and 100 mg and Cohort 6 dose to be determined if the maximum tolerated dose (MTD) was not reached. Anticipated enrollment was 48.

This study enrolled 47 participants and consisted of 6 Cohorts. Participants in Cohorts 1, 2, 3, 5 and 6 were randomized to receive a single dose of TAK-137 or placebo after a 10-hour fast. Participants in Cohort 4 were randomized to receive a single dose of TAK-137 or placebo under fasted conditions, followed by a single dose of TAK-137 or placebo under fed conditions 14 days later. Participants in cohort 4 will receive the same dose in both fasted and fed conditions. The starting dose was 2 mg followed by administrations of 5, 10, 0.5 and 20 mg.

This single-center trial was conducted in the United States. For Cohorts 1, 2, 3, 5, and 6 the overall time to participate in this study was up to 42 days. Participants made 4 visits to the clinic including one 5-day period of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

For Cohort 4 the overall time to participate in this study was up to 56 days. Participants made 7 visits to the clinic including two 5-day periods of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Is a healthy male or non-pregnant, non-lactating female adult who is 18 to 55 years of age inclusive at the time of informed consent and first study medication dose.
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. Is able to comply with the protocol and is willing to sign the informed consent prior to undergoing any study-related procedures.

Exclusion Criteria:

1. Has a known hypersensitivity to any component of the formulation of TAK-137.
2. Has a medical condition such as mental retardation that can cause cognitive impairment.
3. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale \[C-SSRS\] or has made a suicide attempt in the previous 6 months).
4. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash.
5. There is any finding in the participant's medical history, physical examination, or safety laboratory tests (including safety electroencephalogram \[EEG\]) giving reasonable suspicion of a disease that would contraindicate taking TAK-137, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
6. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.

Primary outcomes:
measure: Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
timeFrame: Day 1 to 14 days after the last dose of study medication(Up to 30 days)
measure: Percentage of Participants With Abnormal Safety Laboratory Findings
timeFrame: Day 1 to 14 days after the last dose of study medication (Up to 30 Days)
measure: Percentage of Participants With Markedly Abnormal Vital Sign Measurements
timeFrame: Day 1 to 14 days after the last dose of study medication
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-137
timeFrame: Day 1
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137
timeFrame: Day 1
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137
timeFrame: Day 1
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137
timeFrame: Day 1
measure: Terminal Elimination Half-life (T1/2) for TAK-137_101
timeFrame: Day 1
measure: Apparent Clearance (CL/F) for TAK-137_101
timeFrame: Day 1
measure: Apparent Volume of Distribution (Vz/F) for TAK-137_101
timeFrame: Day 1
measure: Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t])
timeFrame: Day 1
measure: Fraction of TAK-137 Excreted in Urine (Fe)
timeFrame: Day 1
measure: Renal Clearance (CLr) for TAK-137
timeFrame: Day 1
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: