Bioequivalence of Single Dose Extended Release Naproxen Sodium (660 mg) Tablet Versus Naproxen Sodium (220 mg) Tablet Three Times Daily

Study Overview
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Brief Summary
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Bioequivalence trial in healthy adult subjects to determine the bioavailability of 3 different sustained release formulations of naproxen 660 mg relative to the established commercial Aleve 220 mg tablet.

Official Title
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A Pilot Four-Way Crossover Bioequivalence Trial of Sustained Release Forms of Naproxen Versus Aleve Tablets in Healthy Adult Subjects in a Fasted State

Conditions
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Pain

Intervention / Treatment
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* Drug: Naproxen Sodium ER (BAY117031), 20% HPMC
* Drug: Naproxen Sodium ER (BAY117031), 30% HPMC
* Drug: Naproxen Sodium ER (BAY117031), 40% HPMC
* Drug: Aleve (Naproxen Sodium, BAY117031)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy ambulatory male and female subjects 18 to 55 years of age, inclusive Body Mass Index (BMI) of approximately 18.0 to 30.0 kg/m2, and a total body weight >50 kg (110 lbs) Results of screening and clinical laboratory tests are within normal limits or considered not clinically significant by the Principal Investigator or Sponsor Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, intramuscular injection or double-barrier and have a negative pregnancy test at Screening and on Day 0 of each treatment period. Female subjects of nonchildbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy. Provide a personally signed and dated informed consent prior to inclusion in the trial indicating that the subject has been informed of all pertinent aspects of the trial. Exclusion Criteria: History of hypersensitivity to aspirin (ASA), naproxen sodium, or acetaminophen, and similar pharmacological agents or components of the products History of gastrointestinal bleeding or perforation, including bleeding related to previous NSAID therapy. Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding). Have taken ASA, ASA-containing products, acetaminophen (acetyl-para-amino-phenol or APAP) or any other NSAID (OTC or prescription) 7 days prior to dosing or during the treatment period, other than study treatment Loss of blood in excess of 500 mL within 56 days of the first dose of trial treatment (e.g., donation, plasmapheresis, or injury) Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) Positive alcohol or drug screen at Screening or on Day 0 of Treatment Periods 1 or 2 Females who are pregnant or lactating Smokers or currently consuming any type of tobacco product(s) including any smoking cessation nicotine-containing product (eg, nicotine patch, nicotine gum).

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naproxen sodium extended release 660 mg, 20% HPMC<br>Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve (Naproxen sodium) 220 mg tablet | Drug: Naproxen Sodium ER (BAY117031), 20% HPMC<br>* 1 tablet 660 mg administered orally once daily<br>|
| Experimental: Naproxen sodium extended release 660 mg, 30% HPMC<br>Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve 220 mg tablet | Drug: Naproxen Sodium ER (BAY117031), 30% HPMC<br>* 1 tablet 660 mg administered orally once daily<br>|
| Experimental: Naproxen sodium extended release 660 mg, 40% HPMC<br>Bioequivalence in healthy adult subjects in a fasted state relative to the established commercial Aleve 220 mg tablet | Drug: Naproxen Sodium ER (BAY117031), 40% HPMC<br>* 1 tablet 660 mg administered orally once daily<br>|
| Active Comparator: Naproxen sodium 220 mg<br>Bioequivalence in healthy adult subjects in a fasted state | Drug: Aleve (Naproxen Sodium, BAY117031)<br>* 1 tablet 220 mg administered orally three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum plasma concentration) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC0-24 (partial area under the curve ) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC0-t (areas under the curve ) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC0-∞ (area under the curve) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| Tmax (The first time point where Cmax is reached) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC0-8 (partial area under the curve) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC8-16 (partial area under the curve ) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| AUC16-24 (partial area under the curve) for naproxen sodium |  | Days 0, 1, 2, and 3 | 
| λz (terminal elimination rate constant) |  | Days 0, 1, 2, and 3 | 
| t1/2 (terminal half life) |  | Days 0, 1, 2, and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) collection |  | up to 50 days | 
| Serious adverse events (SAEs) collection |  | up to 50 days | 
| Vital signs: sitting blood pressure |  | up to 50 days | 
| Vital signs: repiratory rate |  | up to 50 days | 
| Vital signs : pulse rate |  | up to 50 days | 
| Clinical Laboratory data | Blood and urine samples were collected according to standard medical guidelines at the Screening Visit. In addition, hematology and chemistry were obtained at the end of the study (EOS). | up to 50 days | 
| Physical examination findings | Brief physical examination, including height, weight and BMI, was performed at the Screening Visit and at EOS | up to 50 days |