Clinical trial NCT03456960: A Study to Evaluate the Bioequivalence (BE) and the Food Effect of TAK-438ASA Tablet
Official title: A Phase 1, Randomized, Open-Label, Crossover Study to Evaluate the Bioequivalence of Single Oral Dose of TAK-438ASA Tablet and Single Oral Dose of TAK-438 Tablet Plus Aspirin Enteric-Coated Tablet (Study 1) and the Food Effect of Single Oral Dose of TAK-438ASA Tablet (Study 2) in Healthy Adult Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-03-07
Enrollment: 276
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 purposes of this study are to evaluate BE between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 milligram (mg) and aspirin enteric-coated tablet 100 mg in Japanese healthy adult men (Study 1), and to evaluate the effects of food on the pharmacokinetics of TAK-438ASA tablet in Japanese healthy adult men (Study 2).

Detailed description: The drug under investigation in this study is called TAK-438ASA. TAK-438ASA is being tested in Japanese healthy adult men. This study consists of two studies to evaluate bioequivalence (Study 1) and the effects of food (Study 2). Study 1 (split into a Pilot phase and a Pivotal phase) will look at bioequivalence between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 mg and aspirin enteric-coated tablet 100 mg. Study 2 will look at the effects of food on the pharmacokinetics of TAK-438ASA tablet.

The study will enroll up to 440 participants in total (Study 1 + 2). For Study 1, 12 participants per group (24 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups for the pilot study to estimate the sample size of Pivotal study. After pilot study, 202 participants as a maximum per group (404 participants in total) will be randomly assigned to one of the two treatment groups:

* TAK-438ASA tablet (Period 1) + TAK-438 10 mg tablet and Aspirin 100 mg tablet (Period 2)
* TAK-438 10 mg tablet and Aspirin 100 mg tablet (Period 1) + TAK-438ASA tablet (Period 2)

For Study 2, 6 participants per group (12 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

* TAK-438ASA tablet (Fasted condition) + TAK-438ASA tablet (Fed condition)
* TAK-438ASA tablet (Fed condition) + TAK-438ASA tablet (Fasted condition) This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 18 days. Participants will make two visits to the clinic and be hospitalized for eight days in total.

Eligibility criteria: Inclusion Criteria:

1. In the opinion of the investigator or sub-investigator, participants are capable of understanding the procedures required for the study and complying with its requirements.
2. Participants sign and date an informed consent form by themselves prior to the initiation of any study procedures.
3. Japanese healthy men aged greater than or equal to (\>=) 20 and less than or equal to (=\<) 60, inclusive, at the time of consent.
4. Body weight \>=50 kilogram (kg) as well as body mass index (BMI) \>=18.5 kilogram per meter square (kg/m\^2) and =\<25.0 kg/m\^2 at screening test.

Exclusion Criteria:

1. Participants who received study drug within 16 weeks (112 days) prior to the start of study treatment in Period 1.
2. Participants who received TAK-438 or aspirin in a previous study.
3. Staffs at the study site and their family, or participants who depend on the study-related staffs at the study site (example, husband and wife, parents, children, brothers and sisters), or participants who may be constrained to consent to the study.
4. Participants with uncontrolled and clinically significant neurological, cardiovascular, lung, hepatic, renal, metabolic, gastrointestinal, urinary or endocrine disease, or other abnormalities (except for diseases investigated) that might affect the study participation or impact the results of the study.
5. Participants with a previous or current history of aspirin asthma (asthmatic attack induced by non-steroidal anti-inflammatory drugs, etc.).
6. Participants with hypersensitivity for components of TAK-438 tablet or aspirin enteric-coated tablet, or salicylic acid-based products.
7. Positive result in urinary test for illegal drug abuse at screening.
8. Participants who have a history of illegal drug abuse or alcoholism within the past 2 years prior to the screening visit, or who are not willing to refrain from alcohol consumption and drug use during the study period.
9. Participants who ingested a medicine, a supplement or food forbidden to be used in combination during the specified time period.
10. Participants with a current history or recent episodes (within the past 6 months) of gastrointestinal diseases (malabsorption, gastroesophageal reflux, peptic ulcer disease, erosive oesophagitis), frequent (at least once per week) heartburn or surgical intervention that might affect drug absorption.
11. Participants with a history of cancer, except for basal cell carcinoma in remission for \>=5 years prior to Day 1.
12. Positive results at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological test for syphilis.
13. Participants who have difficulties in blood draw from peripheral veins.
14. Participants who had \>=200 milliliter (mL) of whole blood drawn within 4 weeks (28 days) prior to the start of study treatment in Period 1 or who had \>=400 mL of whole blood drawn within 12 weeks (84 days) prior to the start of study treatment in Period 1.
15. Participants who had a total of \>=800 mL of whole blood drawn within 52 weeks (364 days) prior to the start of study treatment in Period 1.
16. Participants who had blood components drawn within 2 weeks (14 days) prior to the start of study treatment in Period 1.
17. Clinically significant abnormalities in electrocardiogram at screening or admission (Day -1).
18. Participants with abnormal laboratory parameters suggestive of clinically significant underlying diseases or who have abnormal values in the following measures at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) over the upper limit of normal.
19. Participants who are unlikely to comply with the protocol or deemed ineligible due to other reasons by the principal investigator or other investigators.

Primary outcomes:
measure: Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Secondary outcomes:
measure: Study 1, 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) post-dose
measure: Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin
timeFrame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Fukuoka Mirai Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: