Study to Assess the Bioequivalence Between D961S and Esomeprazole/Buffered Acetylsalicylic Acid (ASA) in Japanese Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess bioequivalence between D961S and esomeprazole/buffered ASA, safety, tolerability of esomeprazole in combination with ASA and pharmacokinetics (PK) of D961S, esomeprazole and buffered ASA following repeated administration in healthy male Japanese subjects.

Detailed Description
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A Phase I, Open label, Randomized, Single center, 2 way Crossover Bioequivalence Study Comparing D961S (a Fixed-dose Combination Capsule of Esomeprazole 20 mg and Acetylsalicylic Acid 81 mg) with a Free Combination of Esomeprazole Capsule 20 mg + Buffered Acetylsalicylic Acid Tablet 81 mg After Repeated Oral Administration in Japanese Healthy Male Subjects

Official Title
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A Phase I, Open Label, Randomized, Single Center, 2 Way Crossover Bioequivalence Study Comparing D961S (a Fixed-dose Combination Capsule of Esomeprazole 20 mg and Acetylsalicylic Acid 81 mg) With a Free Combination of Esomeprazole Capsule 20 mg + Buffered Acetylsalicylic Acid Tablet 81 mg After Repeated Oral Administration in Japanese Healthy Male Subjects

Conditions
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Bioequivalence Study

Intervention / Treatment
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* Drug: D961S
* Drug: Esomeprazole
* Drug: Buffered acetylsalicylic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese males 20-45 years of age Classified as homo-EM Negative for HIV, Hepatitis B, Hepatitis C and syphilis Body Mass Index (BMI=weight/height2) 19-27 (kg/m2) Body weight 50-85 kg Exclusion Criteria: Significant clinical illness from 2 weeks preceding the pre-entry visit to the randomization Past or present cardiac, renal, hepatic, neurological or gastrointestinal disease Need for concomitant medication in the study Past or present NSAIDs induced asthma History of bleeding diathesis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D961S<br>2 way crossover | Drug: D961S<br>* Oral gelatine capsule<br>|
| Experimental: esomeprazole + buffered acetylsalicylic acid<br>2 way crossover | Drug: Esomeprazole<br>* Oral HPMC capsule<br>* Other names: Nexium® capsule 20 mg;Drug: Buffered acetylsalicylic acid<br>* Tablet<br>* Other names: Bufferin Combination Tablet A81;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of bioequivalence of D961S to combination of esomeprazole + buffered ASA in terms of Area under the plasma concentration(AUCτ). | All PK variables at each time point will be listed by subject and summarised for each treatment using appropriate descriptive statistics. | Baseline, which is 30 minutes before dose at day 5 of treatment period, till day 6 | 
| Description of bioequivalence of D961S to combination of esomeprazole + buffered ASA in term maximum plasma concentration (Cmax,ss) | All PK variables at each time point will be listed by subject and summarised for each treatment using appropriate descriptive statistics. | Baseline, which is 30 minutes before dose at day 5 of treatment period, till day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of D961S PK profile comparing to esomeprazole and ASA combination in terms of AUC0-t,ss, mean residence time (MRT), time to reach Cmax (tmax,ss) and t1/2,ss of esomeprazole and ASA, and AUCτ, Cmax,ss, AUC0-t,ss, MRT, tmax,ss and t1/2,ss of SA | All PK variables and plasma concentrations of esomeprazole, ASA and SA at each time point will be listed by subject and summarised for each treatment using appropriate descriptive statistics. | Baseline, which is 30 minutes before dose at day 5 of treatment period, till day 6 | 
| Description of Safety and tolerability profile of esomeprazole in combination with ASA in terms of adverse events, clinical laboratory tests, blood pressure, pulse rate and body temperature. | Descriptive statistics will be provided for all safety variables, and the analyses will be performed according to the actual treatment. No formal comparison will be performed. | Pre-entry, Day 5 of treatment period and follow up (5-7 days after last dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteer, Japanese males, homo-EM