Clinical trial NCT02402530: Efficacy and Safety of Intravenous Neridronic Acid in CRPS-I
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Complex Regional Pain Syndrome, Type I
Keywords: Neridronic Acid
Neridronate
CRPS
RSD
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2015-03-30
Enrollment: 459
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in the Pain Intensity Score to Week 12.
timeFrame: Baseline; Week 12
Secondary outcomes:
measure: Response to treatment: Proportion of Participants With at Least 30 Percent Reduction in the Pain Intensity Score
timeFrame: Baseline; Week 12
measure: Response to treatment: Proportion of Participants With at Least 50 Percent Reduction in the Pain Intensity Score
timeFrame: Baseline; Week 12
measure: Change in the Brief Pain Inventory (BPI) Interference Score
timeFrame: Baseline; Week 12
measure: Patient Global Impression of Change (PGIC)
timeFrame: Baseline; Week 12
measure: Change in the EuroQol-5 Dimension 5 Level (EQ-5D-5L) Index Score
timeFrame: Baseline; Week 12
measure: Change in the EuroQol Visual Analog Scale (EQ VAS)
timeFrame: Baseline; Week 12
Other outcomes:
measure: Change in the Worst Pain Intensity
timeFrame: Baseline; Week 12
measure: Change in the Average Pain Intensity
timeFrame: Baseline; Week 12
measure: Change from Baseline in the Pain Intensity Scores at Each Week
timeFrame: Baseline to Week 12
measure: Response to Treatment: Proportion of Participants with 0 to 100% Decrease in the Pain Intensity Score
timeFrame: Baseline; Week 12
measure: Response to Treatment: Proportion of Participants With at Least a 2 Point Decrease in the Pain Intensity Score
timeFrame: Baseline; Week 12
measure: Change in the Pain Anxiety Symptom Scale (PASS) Total Score
timeFrame: Baseline; Week 12
measure: Change in the Center for Epidemiological Studies Depression (CES-D) Scale Total Score
timeFrame: Baseline; Week 12
measure: Change in Pain Disability Index (PDI)
timeFrame: Baseline; Week 6; Week 12
measure: Change in the Medical Outcomes Study (MOS) Sleep Scale: Sleep Problems Index
timeFrame: Baseline; Week 6; Week 12
measure: Change in Pain Medication Score
timeFrame: Baseline; Week 6; Week 12; Month 6; Month 9; Month 12
measure: Change in the Current Pain Intensity in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the Average Pain Intensity in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the Worst Pain Intensity in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the BPI Interference Score in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: PGIC in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the EQ-5D-5L Index Score in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the EQ VAS in the Extended Follow-up Period
timeFrame: Baseline; Month 6; Month 9; Month 12
measure: Change in the Complex Regional Pain Syndrome (CRPS) Severity Score
timeFrame: Baseline; Week 6; Week 12; Month 6; Month 9; Month 12
measure: Presence or Absence of Complex Regional Pain Syndrome (CRPS)
timeFrame: Month 6; Month 9; Month 12
measure: Change from Baseline in Bone Turnover Markers
timeFrame: Baseline to Month 12
Locations:
city: Foley
country: United States
facility: Site US119 - G & L Research
state: Alabama
city: Scottsdale
country: United States
facility: Site US117 - Valley Pain Consultants
state: Arizona
city: Scottsdale
country: United States
facility: Site US116 - Arizona Pain Specialists
state: Arizona
city: Tucson
country: United States
facility: Site US124 - Quality of Life Medical and Research Centers LLC
state: Arizona
city: Little Rock
country: United States
facility: Site US154 - Woodland International Research Group
state: Arkansas
city: Anaheim
country: United States
facility: Site US110 - Orange County Research Institute
state: California
city: Cerritos
country: United States
facility: Site US172 - Core Healthcare Group
state: California
city: Chino
country: United States
facility: Site US108 - Catalina Research Institute
state: California
city: Colton
country: United States
facility: Site US175 - Inland Pain Medicine
state: California
city: La Jolla
country: United States
facility: Site US152 - UC San Diego Healthcare Systems, Center for Pain Medicine
state: California
city: Los Gatos
country: United States
facility: Site US102 - Samaritan Center for Medical Research
state: California
city: Sacramento
country: United States
facility: Site US126 - Northern California Research
state: California
city: Denver
country: United States
facility: Site US106 - Mountain View Clinical Research
state: Colorado
city: Clearwater
country: United States
facility: Site US153 - Clinical Research of West Florida Inc - Clearwater
state: Florida
city: Clermont
country: United States
facility: Site US162 - South Lake Pain Institute
state: Florida
city: Merritt Island
country: United States
facility: Site US143 - Florida Pain Institute
state: Florida
city: Miami Lakes
country: United States
facility: Site US122 - Precision Research Organization, LLC
state: Florida
city: Miami
country: United States
facility: Site US111 - Sunrise Research Institute
state: Florida
city: Orlando
country: United States
facility: Site US104 - Discovery Clinical Trials
state: Florida
city: Plantation
country: United States
facility: Site US133 - Gold Coast Research LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Site US171 - Florida Medical Pain Management
state: Florida
city: Tampa
country: United States
facility: Site US121 - Clinical Research of West Florida
state: Florida
city: West Palm Beach
country: United States
facility: Site US165 - Palm Beach Research
state: Florida
city: Newnan
country: United States
facility: Site US131 - Better Health Clinical Research, Inc
state: Georgia
city: Chicago
country: United States
facility: Site US103 - Great Lakes Clinical Trials
state: Illinois
city: Overland Park
country: United States
facility: Site US129 - International Clinical Research Institute
state: Kansas
city: Boston
country: United States
facility: Site US169 - Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Site US127 - Advance Clinical Research, Inc
state: Missouri
city: Las Vegas
country: United States
facility: Site US105 - Advanced Biomedical Research of America
state: Nevada
city: Princeton
country: United States
facility: Site US101 - Princeton Medical Institute
state: New Jersey
city: Shrewsbury
country: United States
facility: Site US151 - Premier Pain Centers
state: New Jersey
city: Somerset
country: United States
facility: Site US156 - University Clinical Research Center
state: New Jersey
city: Albany
country: United States
facility: Site US166 - Albany Medical College
state: New York
city: Bronx
country: United States
facility: Site US137 - Montefiore Medical Center
state: New York
city: Rochester
country: United States
facility: Site US145 - University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Site US135 - The Center for Clinical Research
state: North Carolina
city: Middleburg Heights
country: United States
facility: Site US157 - North Star Medical Research
state: Ohio
city: Philadelphia
country: United States
facility: Site US149 - Founders Research Corporation
state: Pennsylvania
city: Willow Grove
country: United States
facility: Site US114 - Abington Neurological Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Site US112 - Clinical Trials of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Site US107 - Austin Center for Clinical Research
state: Texas
city: Austin
country: United States
facility: Site US134 - Lovelace Scientific Resources, Inc
state: Texas
city: Houston
country: United States
facility: Site US113 - Pioneer Research Solutions, Inc
state: Texas
city: Salt Lake City
country: United States
facility: Site US118 - Omega International Pain Clinic
state: Utah
city: West Jordan
country: United States
facility: Site US164 - Advanced Clinical Research
state: Utah
city: Bellevue
country: United States
facility: Site US144 - Bellevue Surgery Center
state: Washington
city: Bellevue
country: United States
facility: Site US173 - Bellevue Surgery Center
state: Washington
city: Bellevue
country: United States
facility: Site US123 - Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Site US161 - Swedish Pain and Headache Center
state: Washington
city: Böhlen
country: Germany
facility: Site DE107 - Studienzentrum A. Schwittay
city: Fellbach
country: Germany
facility: Site DE104 - Schmerzzentrum Dr. med. C. Wachter & T. Tusker
city: Hannover
country: Germany
facility: Site DE101 - Klinische Forschung Hannover Mitte GmbH
city: Munich
country: Germany
facility: Site DE103 - Algesiologikum Studienzentrum und Algesiologikum MVZ
city: Würzburg
country: Germany
facility: Site DE102 - Universitätsklinikum Würzburg Neurologische Klinik
city: Cambridge
country: United Kingdom
facility: Site GB104 - The Royal Victoria Infirmary
city: Darlington
country: United Kingdom
facility: Site GB108 - Darlington Memorial Hospital, Centre for Research and clinical Intervention
city: Exeter
country: United Kingdom
facility: Site GB109 - Royal Devon Exeter Hospital
city: London
country: United Kingdom
facility: Site GB101 - Guys and St. Thomas NHS Foundation Trust - St Thomas Hospital
city: London
country: United Kingdom
facility: Site GB111 - Chelsea and Westminster Hospital - NHS Foundation Trust
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References: