Safety of intravenous neridronic acid in complex regional pain syndrome (CRPS)

Phase 1

Conditions: Complex regional pain syndrome (CRPS)
MedDRA version: 20.1 Level: LLT Classification code 10064334 Term: Complex regional pain syndrome Type I System Organ Class: 100000004852
MedDRA version: 20.1 Level: LLT Classification code 10064335 Term: Complex regional pain syndrome Type II System Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2016-001164-11-DE

Lead Sponsor: Grünenthal GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 290

Inclusion Criteria

1. Informed consent signed.
2. Male or female subjects at least 18 years of age at Visit 1.
3. A diagnosis of CRPS according to the clinical diagnostic criteria recommended by the International Association for the Study of Pain (IASP; Budapest clinical criteria”).
4. Ongoing moderate to severe chronic pain, including a baseline current pain intensity score of 4 or greater using an 11-point NRS, referring to the CRPS-affected limb.
5. In stable treatment and follow-up therapy for CRPS for at least 1 month prior to allocation to treatment.
6. Women of child-bearing potential must have a negative urine (ß-HCG) pregnancy test and must be using 2 forms of medically
acceptable contraception.
7. Subjects 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.
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 258
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

1. Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2 or a urinary albumin creatinine Ratio greater than 30 mg/g). Note: If 2 consecutive laboratory tests
indicate eGFR levels greater or equal to 60 mL/min/1.73 m2 or a single
repeat laboratory test of the urinary albumin creatinine ratio is less than
30 mg/g during the enrollment period, the subject is eligible.
2. Serum calcium or magnesium outside of the central laboratory’s reference range.
3. Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL.
4. Corrected QT interval (QTcF) greater than 470 ms; serum potassium outside the central laboratory’s reference range; clinically unstable cardiac disease; evidence of complete left bundle branch block; complete atrioventricular block; history of Long QT Syndrome or a relative with this condition; or any other known risk factor for torsade de pointes.
5. Subjects receiving medications with a known risk of torsades de pointes within 7 days prior to allocation. Subjects receiving selective serotonin re-uptake inhibitor antidepressants (e.g., citalopram, escotalopram) or tricyclic antidepressants are eligible if the QT-interval
values do not meet the exclusion criteria, the medication was started at least 1 month prior to allocation, the dose is stable, and the dose is anticipated to remain stable until at least 4 days after the last infusion of IMP.
6. Anticipated requirement for treatment with oral or intravenous bisphosphonate for another condition, or administration of denosumab, or other drugs affecting bone turnover or bone metabolism within 6 months prior to Visit 1.
7. History of any allergic or hypersensitivity reaction to neridronic acid or other bisphosphonate, acetaminophen, or to vitamin D or calcium supplements.
8. Recent tooth extraction or other invasive dental procedure, unhealed or infected extraction site, or significant dental/periodontal disease that may predispose to need for tooth extraction or other invasive dental procedures during the trial.
9. Evidence of denture-related gum trauma or improperly fitting dentures causing injury.
10. Prior radiation therapy of the head or neck.
11. History of malignancy within 2 years prior to Visit 1, with the exception of basal cell carcinoma.
12. 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 Visit 1.
13. Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within 2 years of Visit 1.
14. 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 subject’s safety during trial participation.
15. Women who are pregnant or breastfeeding.
16. Elevated aspartate aminotransferase or alanine aminotransferase greater than 2-fold upper limit of normal or current evidence of chronic liver disease.
17.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of neridronic acid in subjects with complex regional pain syndrome.;<br> Secondary Objective: To assess the safety and tolerability of neridronic acid in subjects with complex regional pain syndrome.<br> To assess the efficacy of neridronic acid in treatment of complex regional pain syndrome.<br> ;Primary end point(s): Occurrence of any treatment emergent adverse event (TEAE).;Timepoint(s) of evaluation of this end point: TEAE occurrence from baseline to Week 52.

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1) Occurrence of permanent discontinuation from treatment due to an adverse event.<br> 2) Change in the current pain intensity score, using a numerical rating scale (NRS).<br> 3) Response to treatment, defined as at least 30% and at least 50% decrease from baseline in the current pain intensity score.<br> 4) Patient Global Impression of Change (PGIC).<br> 5) Change in the Pain Interference score of the Brief Pain Inventory (BPI).<br> ;<br> Timepoint(s) of evaluation of this end point: 1) Day 1 to Day 10<br> 2) Baseline to Week 12 and Week 26<br> 3) at Week 12 and Week 26<br> 4) at Week 12 and Week 26<br> 5) Baseline to Week 12 and Week 26<br>

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