Single-Dose Phase 1 Study of TAK-792

A Randomized, Single-Center, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Oral Dose of TAK-792 in Healthy Subjects

The purpose of this study is to characterize the safety and tolerability profile of TAK-792 when administered as a single oral dose in healthy Japanese and Caucasian male participants.

Study Overview

• Status: Completed
• Conditions: Healthy Male Adults Participants
• Intervention / Treatment: Drug: TAK-792 30 mg; Drug: TAK-792 30 mg placebo; Drug: TAK-792 100 mg; Drug: TAK-792 100 mg placebo; Drug: TAK-792 250 mg; Drug: TAK-792 250 mg placebo; Drug: TAK-792 500 mg; Drug: TAK-792 500 mg placebo; Drug: TAK-792 750 mg; Drug: TAK-792 750 mg placebo; Drug: TAK-792 1250 mg; Drug: TAK-792 1250 mg placebo

Detailed Description

This study will be double-blind and placebo-controlled to avoid subjective bias in the assessment of safety and tolerability of TAK-792. Sentinel dosing will be used in the first cohort (cohort 1) to ensure adequate safety and tolerability evaluation prior to administering TAK-792 to the remainder of participants within the cohort. The dose escalation to the next cohort for Cohorts 2 to 6 will occur after full review of safety and tolerability of the current cohort, and available pharmacokinetic data up to 24 hours in the preceding cohorts. The planned dose levels are 30, 100, 250, 500, 750 and 1250 mg, to be administered in the morning after a fast of at least 10 hours.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kagoshima, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The participant is a healthy male of Japanese descent (born to Japanese parents and grandparents) or Caucasian descent (born to Caucasian parents and grandparents).
4. The participant is aged 20 to 45 years, inclusive, at the time of informed consent.
5. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) between 18.5 kilogram per square meter (kg/m^2) and 25.0 kg/m^2 for Japanese, BMI between 18.5 kg/m^2 and 30.0 kg/m^2 for Caucasian, inclusive at Screening and Day -1.
6. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.

Exclusion Criteria:.

1. The participant has received any investigational compound within 16 weeks (112 days) prior to the dose of study medication.
2. The participant is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
3. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
4. The participant has a positive urine drug result for drugs of abuse at Screening.
5. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
6. Participant has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.
7. The participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
8. Participant 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.
9. Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy]).
10. Participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.
11. Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at Screening.
12. Participant 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. Cotinine test is positive at Screening.
13. The participant has poor peripheral venous access.
14. The participant has undergone whole blood collection of at least 200 milliliter (mL) within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of study drug administration.
15. The participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of study drug administration.
16. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration.
17. Participant has a Screening abnormal (clinically significant) electrocardiogram (ECG).
18. Participant has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than (>)1.5 the upper limits of normal.
19. Participant who, in the opinion of the investigator or sub-investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1-active; Single oral administration of TAK-792 30 milligram (mg) in Japanese participants	Drug: TAK-792 30 mg; TAK-792 30 mg was administered in the morning after a fast.
Placebo Comparator: Cohort 1-placebo; Single oral administration of TAK-792 30 mg placebo in Japanese participants	Drug: TAK-792 30 mg placebo; TAK-792 30 mg placebo was administered in the morning after a fast.
Experimental: Cohort 2-active; Single oral administration of TAK-792 100 mg in Japanese participants	Drug: TAK-792 100 mg; TAK-792 100 mg was administered in the morning after a fast.
Placebo Comparator: Cohort 2-placebo; Single oral administration of TAK-792 100 mg placebo in Japanese participants	Drug: TAK-792 100 mg placebo; TAK-792 100 mg placebo was administered in the morning after a fast.
Experimental: Cohort 3-active; Single oral administration of TAK-792 250 mg in Japanese participants	Drug: TAK-792 250 mg; TAK-792 250 mg was administered in the morning after a fast.
Placebo Comparator: Cohort 3-placebo; Single oral administration of TAK-792 250 mg placebo in Japanese participants	Drug: TAK-792 250 mg placebo; TAK-792 250 mg placebo was administered in the morning after a fast.
Experimental: Cohort 4-active; Single oral administration of TAK-792 500 mg in Japanese and Caucasian participants	Drug: TAK-792 500 mg; TAK-792 500 mg was administered in the morning after a fast or after breakfast.
Placebo Comparator: Cohort 4-placebo; Single oral administration of TAK-792 500 mg placebo in Japanese and Caucasian participants	Drug: TAK-792 500 mg placebo; TAK-792 500 mg placebo was administered in the morning after a fast or after breakfast.
Experimental: Cohort 5-active; Single oral administration of TAK-792 750 mg in Japanese and Caucasian participants	Drug: TAK-792 750 mg; TAK-792 750 mg was administered in the morning after a fast.
Placebo Comparator: Cohort 5-placebo; Single oral administration of TAK-792 750 mg placebo in Japanese and Caucasian participants	Drug: TAK-792 750 mg placebo; TAK-792 750 mg placebo was administered in the morning after a fast.
Experimental: Cohort 6-active; Single oral administration of TAK-792 1250 mg in Japanese and Caucasian participants	Drug: TAK-792 1250 mg; TAK-792 1250 mg was administered in the morning after a fast.
Placebo Comparator: Cohort 6-placebo; Single oral administration of TAK-792 1250 mg placebo in Japanese and Caucasian participants	Drug: TAK-792 1250 mg placebo; TAK-792 1250 mg placebo was administered in the morning after a fast.

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)		Baseline up to Day 8
Number of Participants With TEAE Related to Vital Signs	Vital signs included body temperature (infra-axillary measurement), supine blood pressure (systolic and diastolic) after the participant has rested for at least 5 minutes, respiratory rate, and pulse (beats per minute [bpm]).	Baseline up to Day 5
Number of Participants With TEAE Related to Body Weight		Baseline up to Day 5
Number of Participants With TEAE Related to Electrocardiograms (ECG)		Baseline up to Day 5
Number of Participants With TEAEs Related to Laboratory Tests	Reported TEAE Related to Laboratory Tests are following; Occult blood positive, Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Blood creatine phosphokinase increased, Blood glucose increased, Blood triglycerides increased, Blood urine present, Protein urine present, and White blood cell count increased.	Baseline up to Day 5
Number of Participants With TEAE Related to Gastrointestinal Symptom Rating Scale (GSRS)	The gastrointestinal (GI) symptoms (abdominal pain, heartburn, acid regurgitation, hunger pains, nausea, borborygmus, abdominal distension, eructation, increased flatus, constipation, diarrhoea, loose stools, hard stools, urgent need for defecation, and feeling of incomplete evacuation) using GSRS questionnaires at each assessment point. The GSRS a 15-item self-administered questionnaire that assesses the impact of GI symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms. TEAEs related to GSRS were reported as follows: Diarrhoea, Constipation, Faeces hard, and Faeces soft.	Baseline up to Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC(0-96): Area Under the Plasma Concentration-time Curve From Time 0 to 96 Hours Postdose for TAK-792F and Its Metabolites M-I and M-II	Day 1: pre-dose and at multiple timepoints (0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 hours post dose; up to 96 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-792F and Its Metabolites M-I and M-II	Day 1: pre-dose and at multiple timepoints (0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 hours post dose; up to 96 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-792F and Its Metabolites M-I and M-II	Day 1: pre-dose and at multiple timepoints (0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 hours post dose; up to 96 hours) post-dose
Tmax: Time to Reach the Cmax for TAK-792F and Its Metabolites M-I and M-II	Day 1: pre-dose and at multiple timepoints (0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 hours post dose; up to 96 hours) post-dose
Urinary Excretion Ratio of TAK-792F and Its Metabolites M-I and M-II as Percentage of TAK-792 Dose From 0 to 96 Hours Postdose	Day 1: pre-dose and at multiple timepoints (6, 12, 24, 36, 48, 72, 96 hours post dose; up to 96 hours) post-dose
AUC(0-2.5): Area Under the Plasma Concentration-time Curve From Time 0 to 2.5 Hours Postdose for Total Branched Chain Amino Acids (BCAA) Parameter in Cohorts 4a-2, 4b-2, 5a-2 and 5b-2	Day -1: pre-dose and Day 1 (2.5 hours post dose)
Cmax: Maximum Observed Plasma Concentration for Total BCAA Parameter in Cohorts 4a-2, 4b-2, 5a-2 and 5b-2	Day -1: pre-dose and Day 1 at multiple time points (0.5, 1, 1.5, 2, 2.5, 4, 5, 6, 10, 11, 12, 24 hours; up to 24 hours) post-dose
Tmax: Time to Reach the Cmax for Total BCAA Parameter in Cohorts 4a-2, 4b-2, 5a-2 and 5b-2	Day -1: pre-dose and Day 1 at multiple time points (0.5, 1, 1.5, 2, 2.5, 4, 5, 6, 10, 11, 12, 24 hours; up to 24 hours) post-dose

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2015
• Primary Completion (Actual): January 28, 2016
• Study Completion (Actual): January 28, 2016

Study Registration Dates

• First Submitted: May 15, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 3, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: TAK-792-1001; U1111-1170-1571 (Other Identifier: WHO); JapicCTI-152897 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.