A Phase 1 Food Effect Study of TAK-536TCH Final Formulation Tablet

Phase 1

Completed

• Conditions: Hypertension
• Interventions: Drug: TAK-536TCH

• Registration Number: NCT02348658
• Lead Sponsor: Takeda

Brief Summary

This is a phase 1, randomized, open-label, crossover study to evaluate the food-effect of single oral dose of TAK-536TCH final formulation tablet in healthy adult male participants.

Detailed Description

The purpose of this study is to evaluate the food effect on the pharmacokinetics and safety of a single oral dose of TAK-536TCH under fasted and fed conditions in the morning in healthy adult male participants.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-15
• Study First Submitted QC: 2015-01-22
• Study First Posted: 2015-01-28
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Status Verified: 2016-03
• Results First Submitted: 2016-03-24
• Results First Submitted QC: 2016-03-24
• Last Update Submitted: 2016-03-24
• Results First Posted: 2016-04-26
• Last Update Posted: 2016-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• 1. In the opinion of the investigator and subinvestigator, the participant is capable of understanding and complying with protocol requirements.

  2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.

  3. The participant is a healthy Japanese adult male. 4. The participant is aged 20 to 35 years, inclusive at the time of informed consent.

  4. The participant weighs at least 50.0 kg and has a body mass index (BMI) from 18.5 to 25.0 kilograms per square meter (kg/m^2), inclusive at Screening.

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Exclusion Criteria

1. Participant has systolic blood pressure less-than (<) 90 millimeters of mercury (mmHg) at Screening.
2. Participant has suspected hypotension and associated physical findings, such as dizziness postural, facial pallor, or cold sweats based on evaluation/physical examination at Screening, on Day -1 of Period 1, or up to administration on the Period 1.
3. The participant has received any study drug within 16 weeks (that is [i.e.], 112 days) prior to study drug administration of Period 1.
4. The participant has received TAK-491*, TAK-536, amlodipine, or hydrochlorothiazide in a previous clinical study or as a therapeutic agent.
5. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, or endocrine disease, or other abnormality (other than the disease studied), which could impact the ability of the participant to participate or potentially confound the study results.
6. Participant has a known hypersensitivity to drugs.
7. Participant has a positive urine drug result for drugs of abuse at Screening.
8. 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 was unwilling to agree to abstain from alcohol and drugs throughout the study.
9. Participant required any prohibited concomitant drugs, vitamins, or food products listed in the prohibited concomitant drugs and foods table.
10. Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention [e.g., cholecystectomy]).
11. Participant has a history of cancer.
12. Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at Screening.
13. Participant has poor peripheral venous access.
14. Participant has undergone whole blood collection of at least 200 mL within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to study drug administration in Period 1.
15. Participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to study drug administration in Period 1.
16. Participant has undergone blood component collection within 2 weeks (14 days) prior to study drug administration in Period 1.
17. Participant has a hemoglobin value of less than 12.5 g/dL in laboratory testing at Screening or prior to study drug administration in Period 1.
18. Participant has a clinically significant ECG abnormality at Screening or prior to study drug administration in Period 1.
19. Participant has abnormal laboratory values at Screening or prior to study drug administration of Period 1 that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is >1.5-fold the upper limits of normal range.
20. Participant who, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fasted dosing followed by fed dosing	TAK-536TCH	Dosing in the fasted state followed by fed dosing
Fed dosing followed by fasted dosing	TAK-536TCH	Dosing in the fed state followed by fasted dosing

Primary Outcome Measures

Name	Time	Method
Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ)	Day 1: predose and at multiple time points (up to 48 hours) postdose in each period
Cmax: Maximum Plasma Concentration for Amlodipine Besilate (AML)	Day 1: predose and at multiple time points (up to 120 hours) postdose in each period
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ	Day 1: predose and at multiple time points (up to 48 hours) postdose in each period	AUC(0-48) is a measure of the area under the plasma concentration time-curve from time 0 to 48 hours postdose.
AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose in Each Period for AML	Day 1: predose and at multiple time points (up to 120 hours) postdose in each period	AUC(0-120) is a measure of the area under the plasma concentration time-curve from time 0 to 120 hours postdose.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ	Day 1: predose and at multiple time points (up to 48 hours) postdose in each period	AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for AML	Day 1: predose and at multiple time points (up to 120 hours) postdose in each period	AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ	Day 1: predose and at multiple time points (up to 48 hours) postdose in each period	AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for AML	Day 1: predose and at multiple time points (up to 120 hours) postdose in each period	AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ	Day 1: predose and at multiple time-points (up to 48 hours) postdose in each period	Urinary excretion ratio (percent \[%\] of dose) of TAK-536, its metabolite M-I, M-II and HCTZ in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period.
Urinary Excretion Ratio of AML	Day 1: predose and at multiple time-points (up to 120 hours) postdose in each period	Urinary excretion ratio (% of dose) of AML in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Number of Participants With TEAEs Related to Vital Signs	Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Number of Participants With TEAEs Related to Body Weight	Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values	Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Number of Participants With Clinical Significant Findings in Electrocardiograms After Study Drug Administration	Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )	Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measurement.