A Bioequivalence Study to Compare VIMOVO Manufactured at AstraZenca AB to VIMOVO Manufactured by Patheon Pharmaceuticals and Marketed Enteric-coated Naproxen Formulation

Study Overview
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Brief Summary
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The primary purpose is to demonstrate the bioequivalence of naproxen administered as VIMOVO manufactured at a new facility in Sweden (AstraZeneca) to that of naproxen administered as VIMOVO manufactured in the USA (Patheon) and to a marketed enteric-coated naproxen formulation.

Detailed Description
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A Phase I, Open-label, Randomised, 3-way Crossover Study to demonstrate Bioequivalence of a Single Oral Dose of Naproxen administered as VIMOVO manufactured at AstraZeneca AB compared to that of VIMOVO manufactured by Patheon Pharmaceuticals and a marketed enteric-coated Naproxen Formulation (Manufactured by Roche) in Healthy Volunteers.

Official Title
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A Phase I, Open-label, Randomised, 3-way Crossover Study to Demonstrate Bioequivalence of a Single Oral Dose of Naproxen Administered as VIMOVO Manufactured at AstraZeneca AB Compared to That of VIMOVO Manufactured by Patheon Pharmaceuticals and a Marketed Enteric-coated Naproxen Formulation (Manufactured by Roche) in Healthy Volunteers

Conditions
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Healthy Volunteers, Bioequivalence

Intervention / Treatment
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* Drug: VIMOVO (AstraZeneca)
* Drug: VIMOVO (Patheon)
* Drug: Marketed enteric-coated naproxen formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female volunteer, aged 18 - 55 years (inclusive) Female volunteers must be non-pregnant and non-lactating and have a negative urine pregnancy test result prior to enrolment into the study. Female volunteers of childbearing potential must be using appropriate birth control during the entire duration of the study Body mass index of = 19 to =30 kg/m2 (inclusive) and weights of = 50 to = 100 kg (inclusive) Exclusion Criteria: Volunteer who is likely to have unrecognized cardiovascular or cerebrovascular disease, based on history or risk factors, or who has a clinical significant ECG finding at screening Uncontrolled hypertension defined as resting systolic pressure >140 mmHg or diastolic pressure >90 mmHg at screening or admission to Period 1 Presence or prior history of abnormal bleeding or bleeding disorders, or any volunteer with significant history of peptic ulcer disease or other acid related gastrointestinal symptoms Any gastrointestinal disease, abnormality or gastric surgery that may interfere with gastric emptying, motility and drug absorption

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: 1<br>Treatment order : A, B, C | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|
| Experimental: 2<br>Treatment order : B, C, A | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|
| Experimental: 3<br>Treatment order : C, A, B | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|
| Experimental: 4<br>Treatment order : A, C, B | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|
| Experimental: 5<br>Treatment order : B, A, C | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|
| Experimental: 6<br>Treatment order : C, B, A | Drug: VIMOVO (AstraZeneca)<br>* VIMOVO (AstraZeneca) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment A;Drug: VIMOVO (Patheon)<br>* VIMOVO (Patheon) 500 mg naproxen/20 mg esomeprazole<br>* Other names: Treatment B;Drug: Marketed enteric-coated naproxen formulation<br>* Marketed enteric-coated naproxen formulation (manufactured by Roche) 500 mg tablet<br>* Other names: Treatment C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in area under the plasma concentration-time curve (AUC) from time zero to infinity |  | Pre-dose to Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse Events as a measure of Safety and Tolerability |  | Day 1 | 
| Number of subjects with Adverse Events as a measure of Safety and Tolerability |  | Day 2 | 
| Number of subjects with Adverse Events as a measure of Safety and Tolerability |  | Day 3 | 
| Number of subjects with Adverse Events as a measure of Safety and Tolerability |  | Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esomeprazole, Phase 1, crossover, bioequivalence, naproxen, vimovo, healthy volunteers