A randomized, double-blind, placebo-controlled 12 week trial of acetaminophen extended release for the treatment of signs and symptoms of osteoarthritis

Abstract

Objective:

Determine efficacy and safety of acetaminophen extended release (ER) 1300 mg given three times daily compared to placebo for relieving signs and symptoms of hip or knee osteoarthritis.

Research design and methods:

Sixty investigators at 58 private, ambulatory, primary care sites in the US enrolled 542 outpatient adults ≥40 years old with moderate to severe idiopathic osteoarthritis pain into a randomized, placebo-controlled, double-blind 12 week clinical trial. Patients were randomly assigned to treatment given three times daily of acetaminophen 1300 mg (n = 267) or placebo (n = 275).

Results:

The three primary endpoints measured through week 12 favored acetaminophen ER as follows: least squares (LS) mean change from baseline for WOMAC physical function subscale score was significantly greater for acetaminophen ER than for placebo (P = 0.011); LS mean patient’s global assessment of response to therapy was significantly greater for acetaminophen ER than for placebo (P = 0.010); and LS mean change from baseline for WOMAC pain subscale score was marginally greater for acetaminophen ER than for placebo (P = 0.054). LS mean change from baseline for secondary endpoints through week 12 also favored acetaminophen ER compared with placebo: significantly for WOMAC stiffness subscale score (P = 0.004), significantly for WOMAC total index score (P = 0.013), and marginally for Nottingham Health Profile energy subscale score (P = 0.057). The percentage of patients with any adverse event was similar for both treatment groups. Hepatic transaminases exceeded 3 × ULN in seven acetaminophen ER patients and one placebo patient. Elevations were attributed to health conditions in three of seven acetaminophen ER patients; elevations in the remaining four patients returned to or toward normal.

Conclusions:

Acetaminophen ER 1300 mg, a nonprescription drug, given three times daily, can provide effective relief of signs and symptoms of osteoarthritis of the hip or knee and was well tolerated.

ClinicalTrials.gov registration number:

ClinicalTrials.gov identifier: NCT00240799.

Keywords::

• Acetaminophen
• Efficacy
• Randomized controlled trial
• Osteoarthritis
• Pain

Transparency

Declaration of funding

This study was conducted, analyzed and supported by McNeil Consumer Healthcare, Fort Washington, PA, USA.

Declaration of financial/other relationships

M.J.P. has disclosed that she is a current employee of McNeil Consumer Healthcare and was an employee of McNeil Consumer Healthcare at the time of conduct of this study. D.D.H. and M.E.F. have disclosed that they were employees of McNeil Consumer Healthcare at the time of conduct of this study.

CMRO peer reviewer 1 has disclosed that he has received sponsorship from Servier, Novartis and IBSA; is the recipient of research/grant funding from Servier, Novartis, IBSA, Rottapharm and Wyeth; and is a consultant/advisor to Servier and Rottapharm. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

We are grateful for and acknowledge the efforts of the 60 investigators who participated in this study, and for the study participants. We also acknowledge the scientific contributions of Edwin K. Kuffner MD and the statistical contributions of Brenda Zimmerman MS, both current employees of McNeil Consumer Healthcare.

Previous presentation: While the primary results from this study have not been previously presented, ALT activity data from this study during early acetaminophen therapy were combined with data from two other osteoarthritis studies and presented by Kuffner et al. (poster number 834) at the American College of Rheumatology meetings in Philadelphia in October 2009. In addition, transient ALT elevations during long-term treatment with acetaminophen in this study and similar osteoarthritis studies were analyzed and summarized in an article by Kuffner et al. in CMRO in 2006 (Curr Med Res Opin 2006;22:2137-48).