Efficacy and safety of twice daily sustained-release paracetamol formulation for osteoarthritis pain of the knee or hip: a randomized, double-blind, placebo-controlled, twelve-week study

Abstract

Objective: Evaluate efficacy and safety of an investigational, twice daily sustained-release (SR) paracetamol formulation in subjects with knee or hip osteoarthritis (OA).

Methods: In this multicenter, double-blind, parallel study (NCT02311881), subjects with hip or knee OA were randomly assigned to SR paracetamol 2 × 1000 mg BID, extended-release (ER) paracetamol 2 × 665 mg TID or placebo for 12 weeks. Primary endpoint was mean change from baseline through 12 weeks in WOMAC Osteoarthritis Index pain. Secondary efficacy endpoints included other WOMAC categories, Global Patient Assessment of Osteoarthritis (GPAOA), Patient Global Assessment of Response to Therapy (PGART) and responder rate.

Results: A total of 676 subjects were included in the analysis population (mITT). Mean change from baseline in WOMAC pain subscale was not significantly greater with SR paracetamol BID versus placebo (LS mean [SE]: −28.25 [1.697] vs. −25.74 [1.713]; p = .163). Reduction in WOMAC physical function and stiffness subscales with SR paracetamol BID was not significantly greater than with placebo (p = .089 and .054, respectively). Significant improvement over placebo was observed for GPAOA (p = .043), PGART (p = .012), and proportion of high-improvement responders (p = .015). Safety and tolerability were consistent with the known profile of paracetamol.

Conclusions: Improvement in WOMAC pain, physical function and stiffness subscales from treatment with SR paracetamol BID versus placebo in subjects with knee or hip OA was not significant. SR paracetamol BID demonstrated significant improvements in GPAOA, PGART, and high-responder rate. High placebo response may have contributed to lack of statistical separation on some outcomes. All interventions were generally well tolerated.

Keywords:

• Acetaminophen
• analgesics
• non-narcotic
• pain
• osteoarthritis
• knee
• osteoarthritis
• hip

Transparency

Declaration of funding

This study was funded by GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA.

Author contributions: study design: K.R., A.C.; enrolled subjects: K.R.; data analysis: A.C.; data interpretation: all authors; manuscript preparation: all authors; manuscript review and revisions: all authors; final approval of manuscript: all authors; accountability for all aspects of the work: all authors.

Declaration of financial/other relationships

S.M. and K.R. have disclosed that they are employees of GlaxoSmithKline. A.C. has disclosed that he was an employee of GlaxoSmithKline at the time of the study. A peer reviewer on this manuscript would like to disclose the following relationships: consultant/speaker and researcher for: Inspirion, Mallinckrodt, Baxter, Purdue Pharma LLP, Grunenthal GmbH, BDSI, ENDO Pharmaceuticals Iroko, DepoMed, Collegium, and Mundi Pharma. Two additional reviewers had no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing and editorial assistance was provided by Peloton Advantage and was funded by GlaxoSmithKline Consumer Healthcare. Joëlle Monnet Gaud of GlaxoSmithKline Consumer Healthcare developed the statistical analysis plan, performed statistical analyses and helped to write/review the manuscript. PPD (a contract research organization) facilitated the conduct of the study.