CREATE-1 Study: CRPS Treatment Evaluation 1 Study
Research type
Research Study
Full title
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 I (CRPS-I)
IRAS ID
184848
Contact name
David Pang
Contact email
Sponsor organisation
Axsome Therapeutics
Eudract number
2015-001527-22
Duration of Study in the UK
1 years, 4 months, 3 days
Research summary
Axsome Therapeutics, Inc. is developing AXS-02 (disodium zoledronate tetrahydrate) for the treatment of pain associated with complex regional pain syndrome (CRPS). There is currently no drug approved for the treatment of CRPS. CRPS is formerly known as reflex sympathetic dystrophy and causalgia and is a disorder characterised by severe pain in a limb accompanied by autonomic,sensory, motor and trophic changes. The sensory changes, which include allodynia and hyperalgesia, are accompanied by movement disorders and joint stiffness. The disorder impairs daily functioning and negatively impacts quality of life. For many patients, the pain and associated loss of function result in significant and sometimes permanent disability.
AXS-02 is the disodium salt of zoledronic acid formulated into tablets for oral delivery. Currently, zoledronic acid is available only as an intravenous formulation. Zoledronic acid is also referred to as zoledronate. It is marketed under the trade names Zometa®, and Reclast®(in the U.S.), and Aclasta® (in the E.U.). Zoledronic acid was first approved in the U.S. in 2001,
This Phase 3, randomised, double-blind, placebo-controlled study is designed to compare the safety and efficacy of AXS-02 with that of placebo in the treatment of CRPS. Approximately 190 subjects will be enrolled. Subjects must be at least 18 years of age and have a confirmed diagnosis of CRPS-I of the upper or lower limb according to the new criteria from the International Association for the Study of Pain, with an average weekly baseline pain intensity score of 5 or greater based on an 11-point (0-10) numeric rating scale (NRS) in the affected limb.
Subjects will be randomly assigned to receive either AXS-02 per week or matching placebo.
A double-blind design is appropriate for assessing the efficacy and safety of AXS-02. Randomization was included to avoid bias. Placebo was chosen as the comparator to show treatment effect. The safety and efficacy assessments used in this study are recognized and validated standards of measurement. The planned dose for this Phase 3 study, AXS-02 once a week for 6 weeks, provides a cumulative systemic dose, based on the oral bioavailability observed in the Phase 1 study, which is consistent with the approved dose for the treatment of Paget’s disease of the bone.
Approximately 95 subjects will be enrolled into each treatment group. The duration of dosing is expected to be 6 weeks.REC name
West of Scotland REC 1
REC reference
15/WS/0149
Date of REC Opinion
9 Sep 2015
REC opinion
Further Information Favourable Opinion