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

A Randomized, Open Label, 2-Period, 2-Treatment, Cross-over Phase 1 Study to Evaluate the Bio-equivalence of Single Oral Dose of TAK-536 Pediatric Formulation and TAK-536 Commercial Formulation in Healthy Adult Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Japanese Healthy Adult Male Participants
• Intervention / Treatment: Drug: TAK-536; Drug: TAK-536

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan
    • Nishi Kumamoto Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 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. 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TAK-536 Granules + TAK-536 Tablet; 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.	Drug: TAK-536; TAK-536 granules.; Drug: TAK-536; TAK-536 tablet.
EXPERIMENTAL: TAK-536 Tablet + TAK-536 Granules; 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.	Drug: TAK-536; TAK-536 granules.; Drug: TAK-536; TAK-536 tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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 Reporting One or More Treatment-emergent Adverse Events (TEAEs)	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.	Baseline up to Day 6 of Intervention Period 2 (Day 18)
Number of Participants With TEAEs Related to Vital Signs		Baseline up to Day 6 of Intervention Period 2 (Day 18)
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)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 10, 2017
• Primary Completion (ACTUAL): March 11, 2017
• Study Completion (ACTUAL): March 11, 2017

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (ESTIMATE): February 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Azilsartan medoxomil
• Other Study ID Numbers: Azilsartan-1004; U1111-1190-0845 (REGISTRY: WHO); JapicCTI-173503 (REGISTRY: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No