A Randomized, Double-blind Trial Investigating the Efficacy and Safety of Intravenous Neridronic Acid in Subjects With Complex Regional Pain Syndrome Type I (CRPS-I)
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Complex Regional Pain Syndrome, Type I
- Sponsor
- Grünenthal GmbH
- Enrollment
- 459
- Locations
- 59
- Primary Endpoint
- Change in the Pain Intensity Score to Week 12.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This clinical trial is being conducted to demonstrate the efficacy of neridronic acid in the treatment of pain associated with complex regional pain syndrome type I (CRPS-I).
The trial is divided into 3 periods: a 60-day enrollment period, a 12-week trial period, and an extended follow-up period with visits at Month 6, Month 9, and Month 12. The extended follow-up period will be terminated for all participants after the last participant enrolled completes their Month 6 visit (Visit 9). The double-blind will be maintained throughout the 12-week trial period and extended follow-up period.
Investigators
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.
Arms & Interventions
Placebo
Matching placebo administered as intravenous infusion on Day 1, Day 4, Day 7 and Day 10
Intervention: Placebo
125 mg Neridronic acid
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
Intervention: Placebo
125 mg Neridronic acid
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
Intervention: Neridronic acid 62.5 mg
250 mg Neridronic acid
Neridronic acid 62.5 mg administered as intravenous infusion on Day 1, Day 4, Day 7 and Day 10
Intervention: Neridronic acid 62.5 mg
Outcomes
Primary Outcomes
Change in the Pain Intensity Score to Week 12.
Time Frame: Baseline; 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.
Secondary Outcomes
- Response to treatment: Proportion of Participants With at Least 50 Percent Reduction in the Pain Intensity Score(Baseline; Week 12)
- Change in the EuroQol-5 Dimension 5 Level (EQ-5D-5L) Index Score(Baseline; Week 12)
- Response to treatment: Proportion of Participants With at Least 30 Percent Reduction in the Pain Intensity Score(Baseline; Week 12)
- Change in the Brief Pain Inventory (BPI) Interference Score(Baseline; Week 12)
- Patient Global Impression of Change (PGIC)(Baseline; Week 12)
- Change in the EuroQol Visual Analog Scale (EQ VAS)(Baseline; Week 12)