A Phase 1 Food Effect Study of Azilsartan (TAK-536) Pediatric Formulation

A Randomized, Open-Label, Cross-over Phase 1 Study to Evaluate the Food Effect of Single Oral Dose of TAK-536 Pediatric Formulation in Healthy Adult Male Subjects

The purpose of this study is to assess the PK of TAK-536 and effect of food on the PK following single oral administration of TAK-536 pediatric formulation in Japanese healthy adult male participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-536

Detailed Description

The drug being tested in this study is called TAK-536. TAK-536 is being tested in Japanese healthy adult male participants. This study will look at the PK and effect of food on the PK following single oral administration of TAK-536 pediatric formulation.

The study will enroll 12 healthy participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups and will receive a single oral dose of 10 mg of TAK-536 pediatric formulation with 200 mL of water according to the following treatments in each period during the study.

• Treatment Group A: single oral administration in the morning under fasted condition (Period 1), followed by single oral administration after breakfast (Period 2)
• Treatment Group B: single oral administration after breakfast (Period 1), followed by in the morning under fasted condition (Period 2)

This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately one month. Participants will make five visits to the clinic and be hospitalized for eight days in total.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Fukuoka Mirai 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. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
3. The participant is a Japanese healthy adult male.
4. The participant ages 20 to 35 years inclusive at the time of informed consent.
5. The participant 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. The participant 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 in Period 1.
2. The participant has received any study drug within 16 weeks (112 days) prior to the study drug administration in Period 1.
3. The participant has received TAK-536 or TAK-491 in a previous clinical study or as a therapeutic agent.
4. The participant 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. The participant has a hypersensitivity to any component of the formulation of TAK-536 or any ARB.
6. The participant has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening.
7. 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.
8. The participant has taken any excluded medication, supplements, dietary products or food products during the specified time periods.
9. The participant has any current or recent (within 6 months prior to the start of the study drug administration in Period 1) 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. The participant 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. The participant has a positive test result for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at Screening.
12. The participant has poor peripheral venous access.
13. 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 the study drug administration in Period 1.
14. The participant 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. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of the study drug administration in Period 1.
16. The participant has an abnormal (clinically significant) ECG at Screening or prior to the study drug administration in Period 1.
17. The participant 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 Transaminase (AST) greater than (>) 1.5× the upper limits of normal (ULN).
18. The 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: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TAK-536 10 mg (fasted) + TAK-536 10 mg (fed); TAK-536 10 milligram (mg) granule formulation (pediatric formulation), once daily on Day 1 of Period 1 (6 days) in the morning under fasted condition, followed by wash-out (6 days), followed by TAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 2 (6 days) after starting breakfast.	Drug: TAK-536; TAK-536 granule formulation
EXPERIMENTAL: TAK-536 10 mg (fed) + TAK-536 10 mg (fasted); TAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 1 (6 days) after starting breakfast, followed by wash-out (6 days), followed by TAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 2 (6 days) in the morning under fasted condition.	Drug: TAK-536; TAK-536 granule formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
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 (up to 48 hours) post-dose
T1/2z: Terminal Disposition Phase Half-life for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
MRT∞, ev: Mean Residence Time From Time 0 to Infinity for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
λz: Terminal Disposition Phase Rate Constant for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
CL/F: Apparent Clearance for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Vz/F: Apparent Volume of Distribution for TAK-536	Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	Baseline up to Day 18 (End of Period 2)
Number of Participants With TEAE Related to Vital Sign	Baseline up to Day 18 (End of Period 2)
Number of Participants With TEAE Related to Body Weight	Baseline up to Day 18 (End of Period 2)
Number of Participants With TEAE Related to Clinical Laboratory Tests (Eosinophil Count Increased)	Baseline up to Day 18 (End of Period 2)
Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECGs)	Baseline up to Day 18 (End of Period 2)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 14, 2018
• Primary Completion (ACTUAL): March 11, 2018
• Study Completion (ACTUAL): March 11, 2018

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (ACTUAL): February 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

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-1005; U1111-1206-5973 (OTHER: WHO); JapicCTI-183856 (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 for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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