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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Naproxen sodium extended release 660 mg, 20% HPMC; 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; 1 tablet 660 mg administered orally once daily
EXPERIMENTAL: Naproxen sodium extended release 660 mg, 30% HPMC; 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; 1 tablet 660 mg administered orally once daily
EXPERIMENTAL: Naproxen sodium extended release 660 mg, 40% HPMC; 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; 1 tablet 660 mg administered orally once daily
ACTIVE_COMPARATOR: Naproxen sodium 220 mg; Bioequivalence in healthy adult subjects in a fasted state	Drug: Aleve (Naproxen Sodium, BAY117031); 1 tablet 220 mg administered orally three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (ACTUAL): May 1, 2007
• Study Completion (ACTUAL): May 1, 2007

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (ESTIMATE): September 15, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): September 15, 2015
• Last Update Submitted That Met QC Criteria: September 11, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: 12656