Efficacy and Safety of Intravenous Neridronic Acid in CRPS-I

Exclusion Criteria

• •A diagnosis of complex regional pain syndrome type II.
• •Documented history or diagnosis of peripheral neuropathy, including diabetic peripheral neuropathy or other metabolic or toxic neuropathy, or any other chronic pain condition that would significantly affect a participant's ability to report CRPS-related pain.
• •Body weight less than 40 kg.
• •Evidence of renal impairment or a history of chronic kidney disease.
• •Serum calcium or magnesium outside of the central laboratory's reference range; history of hypocalcemia; any metabolic disorder anticipated to increase risk for hypocalcemia.
• •Vitamin D deficiency. Participants with vitamin D deficiency prior to enrollment may be enrolled with appropriate supplementation during the enrollment period.
• •Corrected QT interval greater than 470 milliseconds; treatment with medications within the last 30 days prior to allocation to IMP that have potential to prolong the QT interval or anticipated need for such medications during the course of the trial.
• •Any prior use of a bisphosphonate for treatment of CRPS, any prior administration of intravenous bisphosphonate, administration of oral bisphosphonate within the previous year, anticipated requirement for treatment with oral or intravenous bisphosphonate for another condition such as osteoporosis during the trial, or administration of denosumab (Prolia) or other bone turnover suppressing drugs within the past 6 months.
• •History of any allergic or hypersensitivity reaction to neridronic acid or other bisphosphonate, or to vitamin D or calcium supplements.
• •Recent tooth extraction, unhealed or infected extraction site, or significant dental/periodontal disease that may pre-dispose to need for tooth extraction or other invasive dental procedures during the trial.
• •Evidence of denture-related gum trauma or improperly fitting dentures causing injury.
• •Prior radiation therapy of the head or neck (within 1 year of enrollment).
• •Recent treatment with high doses of systemic steroids or anticipated need for concomitant high-dose steroid treatment during the trial.
• •History of malignancy within 2 years before enrollment with the exception of basal cell carcinoma.
• •Daily intake of long- and short-acting or controlled-release opioid analgesics of more than 200 mg morphine equivalents, regimens combining high-dose opioids and benzodiazepines, or any other treatment regimen considered unstable, unsafe, or have potential to affect the interpretation of the trial.
• •Use of nerve blocks, ketamine infusions, intravenous immunoglobulin, acupuncture, electromagnetic field treatment, or initiation/implementation of radiofrequency ablation or other sympathectomy procedures, or peripheral nerve stimulation within 6 weeks prior to allocation to investigational medicinal product.
• •Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within 2 years of enrollment, based on participant history and physical examination and according to the investigator's judgment.
• •Any other severe medical condition, including severe depression, or any other severe mood disorder, that in the opinion of the investigator may affect efficacy or safety assessments or may compromise the participant's safety during trial participation.
• •Participant is engaged in litigation related to their disability from CRPS in which monetary gain or loss (or other compensation) may affect their objective participation in the trial.
• •Women who are pregnant or breastfeeding.
• •Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2-fold upper limit of normal (ULN), or evidence or history of liver disease.
• •Participation in an investigational drug trial within 3 months prior to enrollment, or prior participation in this trial with receipt of any infusion of IMP, even a partial infusion.