Complex regional pain syndrome type I (CRPS-I) MedDRA version: 18.0 Level: LLT Classification code 10064334 Term: Complex regional pain syndrome Type I System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Nerixia 100 mg/8 mL concentrate for solution for infusion
Product Name: Neridronic acid 100 mg/8 mL concentrate for solution for infusion
Product Code: GRT7013
Pharmaceutical Form: Concent
Sponsors
Grünenthal GmbH
Eligibility
Sex/Gender
All
Inclusion 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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-acting and short-acting 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 breastfe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of neridronic acid, versus placebo, in treatment of pain associated with CRPS-I.;Secondary Objective: To assess the effect of neridronic acid on pain interference with daily function. To assess the effect of neridronic acid on Patient Global Impression of Change (PGIC) in response to treatment. To assess the effect of neridronic acid on quality of life. To assess the effect of neridronic acid on signs and symptoms of CRPS. To assess the safety and tolerability of neridronic acid in subjects with CRPS-I. ;Primary end point(s): The primary efficacy endpoint will be the change in the Pain Intensity Score from baseline to Week 12. The Pain Intensity Score, related to the CRPS-affected limb, will be determined from current pain intensity ratings, captured in an electronic diary, using an 11-point numerical rating scale (NRS). Subjects will be asked to rate their current CRPS-related pain intensity twice daily, once in the morning and once in the evening. Subjects rate their pain on this scale from 0 = “no pain” to 10 = “pain as bad as you can imagine”. The Baseline Pain Intensity Score will be calculated as the average of 14 current pain intensity ratings obtained over the 7-day baseline pain assessment phase prior to allocation to IMP, starting from the evening of Day -7 and concluding on the morning of Day 1 prior to IMP administration. At least 10 pain intensity ratings must be available for determination of the Baseline Pain Intensity Score. The Week 12 Pain Intensity Score will be determined in a similar manner (i.e., calculated from ratings obtained during the week prior to Visit 8, culminating with the morning rating on the day of Visit 8). All available ratings (of the 14 possible ratings in this time period) will be used in the calculation. All pain intensity ratings for the primary endpoint will be in reference to the CRPS-affected limb (or most painful limb at the time of screening if more than 1 limb is affected by | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response to treatment, defined as a 30% reduction in the Pain Intensity Score from baseline to Week 12. Response to treatment, defined as a 50% reduction in the Pain Intensity Score from baseline to Week 12. Change in the Brief Pain Inventory (BPI) interference scale score from baseline to Week 12. The Patient Global Impression of Change (PGIC) questionnaire score at Week 12. Change in the EuroQol-5 dimension 5 level (EQ-5D-5L) index score and visual analog scale (VAS) from baseline to Week 12. ;Timepoint(s) of evaluation of this end point: Response to treatment, change in the BPI, change in the EQ-5D-5L: Baseline to Week 12. Patient Global Impression of Change (PGIC) questionnaire score: Week 12. | — |
Countries
Germany, United Kingdom, United States
Contacts
Public ContactGrünenthal Trial Information Desk
Grünenthal GmbH
Outcome results
None listed