A Safety and Effectiveness Study of Acetaminophen (4000 mg/Day) and Naproxen (750 mg/Day) in the Treatment of Osteoarthritis of the Hip or Knee

Condition(s) targeted: Osteoarthritis, Knee; Osteoarthritis, Hip

Intervention: acetaminophen (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Official(s) and/or principal investigator(s):
McNeil Consumer & Specialty Pharmaceuticals Clinical Trial, Study Director, Affiliation: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

The purpose of this study is to compare the long-term safety and effectiveness of acetaminophen (4000 mg per day) and naproxen (750 mg per day) in the treatment of osetoarthritis of the hip or knee.

Official title: A Randomized, Double-Blind, Long-Term Comparative Study Evaluating the Safety and Efficacy of Acetaminophen (4000 mg/Day) and Naproxen (750 mg/Day) in the Treatment of Osteoarthritis of the Hip or Knee

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change from baseline in the WOMAC Osteoarthritis Index pain subscale score at Month 6 or at the final visit at the time of subject discontinuation from baseline during the first six months after baseline.

Secondary outcome: Change from baseline to Month 6 (or Month 12 for subjects participating in Group 1) or final visit in the WOMAC Osteoarthritis Index stiffness and physical function subscale scores.

Detailed description: This is a randomized, double-blind study to compare the long term safety profile and effectiveness of acetaminiphen, given at a dose of 1000 mg every four to six hours, and naproxen, given at a dose of 375 mg twice daily (with matching placeno given four times daily to maintain the blind), in the treatment of osteoarthritis of the hip or knee. There are two groups of subjects. Group 1 has approximately 480 subjects randomized and a treatment duration of 12 months. Group 2 has approximately 80 subjects randomized and a treatment duration of 6 months. The primary measure of efficacy is the change from baseline in the WOMAC Osteoarthritis Index pain subscale at month 6. Safety evaluations, throughout the course of the study, include monitoring adverse events, laboratory tests and assessments of vital signs including respiration rate, pulse, blood pressure, and body weight.

Subjects are instructed to take a dose of medication orally, every 4-6 hours. The acetaminophen subjects take a total daily dose of 4 g of acetaminophen. The naproxen subjects a total daily dose of 750 mg of naproxen. The treatment duration is 12 and 6 months in Group 1 and Group 2, respectively.

Minimum age: 40 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Osteoarthritis of the hip or knee for a minimum of six months duration requiring

treatment with either an analgesic or anti-inflammatory agent on a regular basis (greater than or equal to three days/week) for at least three months

- History of osteoarthritis of the hip or knee characterized by pain of mild or moderate

intensity

- Radiographic evidence of grade 2 or 3 osteoarthritis based on the Kellgren and

Lawrence radiographic entry criteria

- Physical ability must be either American College of Rheumatology (ACR) Functional

Class I or II

- Following the washout period, reports mild to moderately severe pain over the previous

24 hours and demonstrates a minimum increase of 20% in the WOMAC Osteoarthritis Index pain sunscale score, relative to the screening score

Exclusion Criteria:

- History of surgery, including arthroscopy, or major trauma to the study joint in the

previous 12 months

- Radiographic evidence of severe osteoarthritis of the study joint based on the

Kellgren and Lawrence radiographic criteria of grade 4 osteoarthritis

- Signs of active study joint inflammation including redness, warmth, and/or, if

qualifying with osteoarthritis of the knee, a large, bulging effusion of the study knee joint with the loss of normal contour of the joint at the screening visit or at the baseline examination after the washout period

- Morning stiffness of >30 minutes duration

- Significantly incapacitated or disabled and would be categorized as ACR Functional

Class III (able to perform only few or none of the duties of usual occupation or self-care) or IV (largely or wholly incapacitated), or unable to walk without assistive devices

A Safety and Effectiveness Study of Acetaminophen (4000 mg/day) and Naproxen (750 mg/day) in the Treatment of Osteoarthritis of the Hip or Knee

Ending date: June 2003
Last updated: May 18, 2007