Clinical trial NCT02402530 (phase 2/phase 3, status: completed)
Conditions: complex regional pain syndrome, type i
ICD codes: G90.50, G90.511, G90.512, G90.513, G90.519, G90.521, G90.522
Drugs: placebo, neridronic acid 62.5 mg
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent signed.

          -  Male or female participant between 18 years and 80 years of age.

          -  A diagnosis of complex regional pain syndrome type I according to the clinical
             diagnostic criteria using the International Association for the Study of Pain clinical
             diagnostic criteria (Budapest criteria).

          -  Baseline Pain Intensity Score of 4 or greater using an 11-point Numerical Rating Scale
             referring to the CRPS-affected limb.

          -  In stable treatment and follow-up therapy for CRPS type I for at least 1 month.

          -  Participant has undergone a recent regular dental examination.

          -  Women of child-bearing potential must have a negative urine ß-HCG pregnancy test at
             enrollment.

          -  Women of child-bearing potential must practice protocol defined acceptable methods of
             birth control during the trial.

          -  Participants must be able to communicate meaningfully, be able to differentiate with
             regard to location and intensity of the pain, and be able to answer the questions in
             the questionnaires used in this trial.

          -  Compliance with the use of electronic diary assessed prior to allocation to treatment.

        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.