(429) CREATE-1 study: a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of AXS-02 (disodium zoledronate tetrahydrate) administered orally to subjects with Complex Regional Pain Syndrome Type 1 (CRPS-1)

Abstract

The CREATE-1 study is an ongoing Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of AXS-02 for the treatment of pain associated with CRPS-1. AXS-02 is a potent bisphosphonate compound being developed as an orally administered, non-opioid treatment for pain. The proposed mechanism of AXS-02 for the treatment of pain associated with CRPS-1 is multifactorial, including inhibition of osteoclast activity, and potential effects on pro-inflammatory cytokine production. This Phase III trial plans to enroll 190 subjects who will be randomized 1:1 to receive either placebo or AXS-02 once weekly for 6 weeks. The primary endpoint is the mean of the pain intensity difference from Baseline to Week 12, where pain intensity is measured by the weekly average daily pain intensity using the numerical rating scale (NRS). The NRS is an 11-point scale (0-10), reported daily by the subject, where 0 = no pain and 10 = worst pain imaginable. Additional efficacy assessments include: Brief Pain Inventory, pain on motion, signs and symptoms of CRPS, quality of life questionnaires (EQ-5D and SF-MPQ), patient global impression of change, clinician global impression of change, disease recurrence, and markers of bone turnover (sCTX and P1NP). Assessments of safety include assessment of adverse events, vital signs, and clinical laboratory values. Eligible subjects must be recently diagnosed with CRPS-1 and not currently receiving opioids. The study is composed of 4 phases: Screening phase (up to 3 weeks; assessments for eligibility), Baseline phase (1 week; confirm pain score for eligibility), Double-blind Treatment phase (12 weeks; dosing and assessments of efficacy), and Follow-up phase (12 weeks; safety follow-up). An interim analysis will be conducted after 95 patients are enrolled and have completed the double-blind phase of the study.