A Single- and Multiple-Dose Study of the Pharmacokinetics of TAK-491 in Healthy Chinese Participants

Healthy Volunteer Clinical Trial

Official title:

A Randomized, Open-Label and Double-Blind, Placebo-Controlled, Single- and Multiple-Dose, Phase 1 Study of the Pharmacokinetics of TAK-491 40 mg and 80 mg in Healthy Chinese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02541669
• Other study ID #: TAK-491_112
• Secondary ID: U1111-1159-5559
• Status: Completed
• Phase: Phase 1
• Start date: November 20, 2015
• Est. completion date: March 17, 2017

Study information

• Verified date: January 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the pharmacokinetics and safety of single- and multiple-dose of TAK-491 in healthy Chinese participants.

Description:

The drug being tested in this study is called TAK-491. TAK-491 is being tested to treat people who have hypertension. This study will look at the pharmacokinetics of TAK-491 in Chinese participants who take TAK-491.

The study will enroll approximately 64 participants.

The first 16 enrolled participants have been randomly assigned (by chance, like flipping a coin) to 1 of the 2 treatment groups:

• TAK-491 40 mg

• TAK-491 80 mg

All participants will be asked to take 1 tablet at the same time on Day 1 and Day 4 to 10 during the study.

The following 48 randomized participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 3 treatment groups:

• TAK-491 40 mg

• TAK-491 80 mg

• TAK-491 placebo

All participants will be asked to take two tablets at the same time on Day 1 and Day 4 to 10 during the study.

This single-center trial will be conducted in China. The overall time to participate in this study is approximately 52 days. Participants will be admitted in the clinic for the first 12 days, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 17, 2017
• Est. primary completion date: March 17, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Is a healthy adult male or female of Chinese descent.

4. Is aged 18 to 45 years, inclusive, at the time of informed consent and first study medication dose.

5. Has a body mass index (BMI) greater than or equal to (>=) 19.0 kilogram per square meter (kg/m^2) and less than (<) 24.0 kg/m^2, inclusive at Screening.

6. Has clinical laboratory evaluations (including clinical chemistry [fasted for at least 8 hours for the screening assessment], hematology, and complete urinalysis) within the reference range for the testing laboratory, unless the results were deemed by the investigator to be not clinically significant at Screening and Check-in (Day -1).

7. Is willing to refrain from strenuous exercise, from 72 hours before Check-in (Day-1) until after Final Visit.

8. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.

2. Has received TAK-491 in a previous clinical study or as a therapeutic agent.

3. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.

4. Has history of uncontrolled, clinically significant manifestations of metabolic (including diabetes mellitus, hypercholesterolemia, or dyslipidemia), endocrine, hematologic, pulmonary, cardiovascular, gastrointestinal, neurological, rheumatologic, skin and subcutaneous tissue disorders, infectious, hepatic, renal, urologic, immunologic, psychiatric or mood disorders (including any past history of suicide attempt), or a history of lactose intolerance, 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-491 or other AII inhibitors or related compounds.

6. Has a positive urine drug result for drugs of abuse or breath alcohol test at Screening or Check-in (Day -1).

7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year 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, or food products.

9. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.

10. Has current or recent (within 6 months) gastrointestinal disease 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 [example, cholecystectomy]).

11. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.

12. Has positive test result for anti-Human immunodeficiency virus (HIV), anti- hepatitis C virus (HCV) antibodies, or for hepatitis B surface antigen (HBsAg) at Screening.

13. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1). Cotinine test is positive at Screening or Check-in (Day -1).

14. Has poor peripheral venous access.

15. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1.

16. Has a Screening or Check-in (Day -1) abnormal (clinically significant) electrocardiogram (ECG). Entry of any participants with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator.

17. Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than (>) 1.5 times the upper limits of normal.

18. Has a hemoglobin value <12 gram per deciliter (g/dL) at Screening.

19. Has a systolic blood pressure <110 and >=160 millimeter of Mercury (mmHg) or a diastolic blood pressure <60 and >=100 mmHg at Screening or Check-in (Day -1).

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• TAK-491
TAK-491 tablets
• TAK-491 placebo
TAK-491 placebo-matching tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-536 (the Active Moiety Derived From TAK-491) on Day 1		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Cmax: Maximum Observed Plasma Concentration for TAK-536 (the Active Moiety Derived From TAK-491) on Day 10		Day 10 pre-dose and at multiple time points (up to 24 hours) post-dose
Primary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536 (the Active Moiety Derived From TAK-491) on Day 1		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536 (the Active Moiety Derived From TAK-491) on Day 10		Day 10 pre-dose and at multiple time points (up to 24 hours) post-dose
Primary	AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536 (the Active Moiety Derived From TAK-491) on Day 1		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-536 (the Active Moiety Derived From TAK-491) on Day 10		Day 10 pre-dose and at multiple time points (up to 24 hours) post-dose
Primary	Terminal Phase Elimination Half-life (T1/2) for TAK-536 (the Active Moiety Derived From TAK-491) on Day 1		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose