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.

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.