Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of TAK-137 in Healthy Participants

Dose Finding Study Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02334982
• Other study ID #: TAK-137_101
• Secondary ID: U1111-1164-7376
• Status: Completed
• Phase: Phase 1
• First received: January 6, 2015
• Last updated: January 29, 2015
• Start date: June 2013
• Est. completion date: January 2014

Study information

• Verified date: January 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Dose Finding Study

Intervention

Drug:
• TAK-137
TAK-137 tablets
• Placebo
TAK-137 placebo-matching tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event	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 (eg, 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 is defined as an adverse event with an onset that occurs after receiving study drug.	Day 1 to 14 days after the last dose of study medication(Up to 30 days)	Yes
Primary	Percentage of Participants With Abnormal Safety Laboratory Findings	The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study.	Day 1 to 14 days after the last dose of study medication (Up to 30 Days)	Yes
Primary	Percentage of Participants With Markedly Abnormal Vital Sign Measurements	The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study.	Day 1 to 14 days after the last dose of study medication	Yes
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.	Day 1	No
Secondary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137	Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.	Day 1	No
Secondary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137	(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).	Day 1	No
Secondary	AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137	AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.	Day 1	No
Secondary	Terminal Elimination Half-life (T1/2) for TAK-137_101	Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.	Day 1	No
Secondary	Apparent Clearance (CL/F) for TAK-137_101	CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-inf), expressed in liters per hour (L/hr).	Day 1	No
Secondary	Apparent Volume of Distribution (Vz/F) for TAK-137_101	Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by ?z.	Day 1	No
Secondary	Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t])	Total amount of drug excreted in urine from time 0 to time t, calculated as Sum (Cu*Vu), where Cu is the concentration of drug excreted in urine and Vu is the volume of urine excreted.	Day 1	No
Secondary	Fraction of TAK-137 Excreted in Urine (Fe)	Fraction of drug excreted in urine, calculated as Fe=(Ae[0-t]/dose)×100.	Day 1	No
Secondary	Renal Clearance (CLr) for TAK-137	CLr is a measure of apparent clearance of the drug from the urine, calculated as CLr=Ae(0-t)/AUC(0-96).	Day 1	No