A Phase 1, Bio-equivalence Study of TAK-536 Pediatric Formulation

Phase 1

Completed

• Conditions: Japanese Healthy Adult Male Participants
• Interventions: Drug: TAK-536

• Registration Number: NCT03042299
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the bio-equivalence of a single oral administration of TAK-536 pediatric formulation (granules) in comparison with a TAK-536 commercial formulation (tablet) in Japanese healthy adult male participants in an open label, 2-period, 2-treatment, cross-over design.

Detailed Description

The purpose of this study is to evaluate the bio-equivalence of a single oral administration of TAK-536 pediatric formulation (granules) in comparison with a TAK-536 commercial formulation (tablet) in healthy adult male participants in an open label, 2-period, 2-treatment, cross-over design.

Study Timeline

• Study First Submitted: 2017-02-01
• Study First Submitted QC: 2017-02-01
• Study First Posted: 2017-02-03
• Study Start: 2017-02-10
• Primary Completion: 2017-03-11
• Study Completion: 2017-03-11
• Results First Submitted: 2018-02-23
• Results First Submitted QC: 2018-02-23
• Status Verified: 2018-10
• Results First Posted: 2018-10-09
• Last Update Submitted: 2018-10-15
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 14

Inclusion Criteria

1. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
2. Signs and dates a written, informed consent form prior to the initiation of any study procedures.
3. Is a Japanese healthy adult male.
4. Aged 20 to 35 years, inclusive, at the time of informed consent.
5. Weighs at least 50.0 kilogram (kg), and has a body mass index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m^2), inclusive, at Screening.

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Exclusion Criteria

1. Has suspected hypotension with associated physical findings, such as dizziness postural, facial pallor, or cold sweats based on evaluation/physical examination at Screening, on the day before the study drug administration (Day -1) in Period 1, or up to the study drug administration on the Period 1.
2. Has received any study drug within 16 weeks (112 days) prior to the study drug administration in Period 1.
3. Has received TAK-536 or TAK-491 in a previous clinical study or as a therapeutic agent.
4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
5. Has a known hypersensitivity to any component of the formulation of TAK-536 or any angiotensin II receptor blocker (ARB).
6. Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening.
7. 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.
8. Has taken any excluded medication, supplements, dietary products, or food products during the time periods specified in the protocol.
9. Has any current or recent (within 6 months) gastrointestinal diseases that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention).
10. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.
11. 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.
12. Has poor peripheral venous access.
13. 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 the study drug administration in Period 1.
14. Has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of the study drug administration in Period 1.
15. Has undergone blood component collection within 2 weeks (14 days) prior to the start of the study drug administration in Period 1.
16. Has an abnormal (clinically significant) ECG at Screening or prior to the study drug administration in Period 1.
17. Has abnormal laboratory values that suggest a clinically significant underlying disease, or participant with the following laboratory abnormalities at Screening or prior to the study drug administration in Period 1: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than (>) 1.5 * the upper limits of normal (ULN).
18. Who, in the opinion of the investigator or sub-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
TAK-536 Granules + TAK-536 Tablet	TAK-536	TAK-536 10 milligram (mg), granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2.
TAK-536 Tablet + TAK-536 Granules	TAK-536	TAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2.

Primary Outcome Measures

Name	Time	Method
Cmax: Maximum Observed Plasma Concentration for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With TEAEs Related to Vital Signs	Baseline up to Day 6 of Intervention Period 2 (Day 18)
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 6 of Intervention Period 2 (Day 18)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with this treatment or study participation. An AE can therefore be any unfavorable and unintended sign (for example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study participation, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Terminal Disposition Phase Rate Constant (λz) for TAK-536	Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Number of Participants With TEAEs Related to Body Weight	Baseline up to Day 6 of Intervention Period 2 (Day 18)
Number of Participants With TEAEs Related to Electrocardiograms (ECGs)	Baseline up to Day 6 of Intervention Period 2 (Day 18)
Number of Participants With TEAEs Related to Clinical Laboratory Tests	Baseline up to Day 6 of Intervention Period 2 (Day 18)

Trial Locations

Locations (1)

Nishi Kumamoto Hospital; 🇯🇵 Kumamoto, Japan