Clinical trial NCT03808493: A Bioequivalence (BE) Study of TAK-438 Orally Disintegrating (OD) Tablet
Official title: A Randomized, Open-Label, Single-Dose, 2×2 Crossover Phase 1 Study to Evaluate the Bioequivalence of TAK-438 OD (Orally Disintegrating) 20 mg Tablet When Administered Without Water (Study 1) or With Water (Study 2) and TAK-438 20 mg Tablet When Administered With Water in Japanese Healthy Volunteer Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Japanese Healthy Adult Male
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-01-17
Enrollment: 48
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the BE of single oral dose of TAK-438 OD 20 milligram (mg) tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2) in Japanese healthy adult male participants.

Detailed description: The drug being tested in this study is called TAK-438 OD tablet. TAK-438 OD tablet is being tested in Japanese healthy adult men. This study will evaluate bioequivalence of single oral dose of TAK-438 OD 20 mg tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2).

The study will enroll up to 144 participants in total (Study 1 + 2). In Study 1 and 2, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups;

Study 1:

* TAK-438 OD 20 mg tablet without water (Period 1) + TAK-438 20 mg tablet with water (Period 2)
* TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet without water (Period 2)

Study 2:

* TAK-438 OD 20 mg tablet with water (Period 1) + TAK-438 20 mg tablet with water (Period 2)
* TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet with water (Period 2)

This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 11 days. Participants will make two visits to the clinic and be hospitalized for four days each in Periods 1 and 2.

Eligibility criteria: 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 healthy Japanese adult male, aged 20 to 60 years, inclusive, at the time of informed consent.
4. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.5 to 25.0 kilogram per square meter (kg/m\^2), inclusive at Screening.
5. The participant must be a current nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months prior to the start of study drug administration in Period 1.
6. The participant must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram (ECG), and vital sign measurements performed at the Screening Visit and prior to the start of study drug administration in Period 1.

Exclusion Criteria:

1. The participant has received any investigational compound within 16 weeks (112 days) prior to the start of study drug administration in Period 1.
2. The participant has received TAK-438 in a previous clinical study or as a therapeutic agent.
3. The participant is an immediate family member of or a study site employee, or is in a dependent 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. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, or endocrine disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate in the study or potentially confound its results.
5. The participant has hypersensitivity to any component of TAK-438 OD tablet or TAK-438 tablet.
6. The participant has a positive urine drug result for drugs of abuse at Screening.
7. The participant has a history of drug or 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, or food products during the specified time periods.
9. The participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, 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.
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 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 study drug administration in Period 1.
15. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration in Period 1.
16. The participant has a Screening or Check-in (Day -1) ECG that was abnormal (clinically significant).
17. The participant has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above 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.

Primary outcomes:
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Secondary outcomes:
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
measure: λz: Terminal Disposition Phase Rate Constant for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Other outcomes:
Locations:
city: Toshima-ku
country: Japan
facility: Sekino Clinical Pharmacology Clininc
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: