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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
TAK-792 30 mg was administered in the morning after a fast.
TAK-792 30 mg placebo was administered in the morning after a fast.
TAK-792 100 mg was administered in the morning after a fast.
Unnamed facility
Kagoshima, Japan
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: 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 \[bpm\]).
Time frame: Baseline up to Day 5
Number of Participants With TEAE Related to Body Weight
Time frame: Baseline up to Day 5
Number of Participants With TEAE Related to Electrocardiograms (ECG)
Time frame: 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.
Time frame: 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.
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TAK-792 100 mg placebo was administered in the morning after a fast.
TAK-792 250 mg was administered in the morning after a fast.
TAK-792 250 mg placebo was administered in the morning after a fast.
TAK-792 500 mg was administered in the morning after a fast or after breakfast.
TAK-792 500 mg placebo was administered in the morning after a fast or after breakfast.
TAK-792 750 mg was administered in the morning after a fast.
TAK-792 750 mg placebo was administered in the morning after a fast.
TAK-792 1250 mg was administered in the morning after a fast.
TAK-792 1250 mg placebo was administered in the morning after a fast.
Time frame: Baseline up to Day 5
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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