Efficacy and Safety of Intravenous Neridronic Acid in CRPS-I | NCT02402530

ID	Type	Description	Link
U1111-1151-2181	Other Identifier	World Health Organization
2014-001915-37	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Matching placebo administered as intravenous infusion on Day 1, Day 4, Day 7 and Day 10	Drug: Placebo
125 mg Neridronic acid	Experimental	Neridronic acid 62.5 mg administered as intravenous infusion on Day 1 and Day 4; matching placebo administered as intravenous infusion on Day 7 and Day 10	Drug: Placebo Drug: Neridronic acid 62.5 mg
250 mg Neridronic acid	Experimental	Neridronic acid 62.5 mg administered as intravenous infusion on Day 1, Day 4, Day 7 and Day 10	Drug: Neridronic acid 62.5 mg

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Matching placebo administered as intravenous infusion.	125 mg Neridronic acid Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in the Pain Intensity Score to Week 12.	The Pain Intensity Score is the mean value of current pain intensity ratings, obtained twice-daily for 1 week, using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine". All pain intensity ratings for the primary endpoint will be in reference to the CRPS-affected limb.	Baseline; Week 12

Secondary Outcomes

Measure	Description	Time Frame
Response to treatment: Proportion of Participants With at Least 30 Percent Reduction in the Pain Intensity Score	Participants with at least a 30 percent decrease in the Pain Intensity Score will be considered to have responded to treatment. The Pain Intensity Score is determined as for the primary endpoint.	Baseline; Week 12

Other Outcomes

Measure	Description	Time Frame
Change in the Worst Pain Intensity	This will be determined as for the primary endpoint, using worst pain intensity ratings. Participants will rate their worst pain intensity during the previous 12 hours twice each day using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine". Worst pain intensity ratings are in reference to the CRPS-affected limb.	Baseline; Week 12

Eligibility Module

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.

Facility	Status	City	State	ZIP	Country	Contacts
Site US119 - G & L Research		Foley	Alabama	36535	United States
Site US117 - Valley Pain Consultants

ID	Term
D020918	Complex Regional Pain Syndromes
D001342	Autonomic Nervous System Diseases
D009422	Nervous System Diseases
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases