Efficacy and Safety of Intravenous Neridronic Acid in CRPS-I

NCT02402530 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: KF7013-01U1111-1151-21812014-001915-37
• Study Type: interventional
• Target: 459
• Locations: 3 countries
• Sites: 59

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.

Conditions

Complex Regional Pain Syndrome, Type I

Keywords

Neridronic Acid; Neridronate; CRPS; RSD

Outcome Measures

Primary Outcomes (1)

• 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 (6)

• Response to treatment: Proportion of Participants With at Least 30 Percent Reduction in the Pain Intensity Score

  Baseline; Week 12

• Response to treatment: Proportion of Participants With at Least 50 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-5 Dimension 5 Level (EQ-5D-5L) Index Score

  Baseline; Week 12

Other Outcomes (20)

• Change in the Worst Pain Intensity

  Baseline; Week 12

• Change in the Average Pain Intensity

  Baseline; Week 12

• Change from Baseline in the Pain Intensity Scores at Each Week

  Baseline to Week 12

Study Arms (3)

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

Interventions

Placebo DRUG

Matching placebo administered as intravenous infusion.

125 mg Neridronic acid; Placebo

Neridronic acid 62.5 mg DRUG

Neridronic acid administered as intravenous infusion.

125 mg Neridronic acid; 250 mg Neridronic acid

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (59)

Site US119 - G & L Research

Foley, Alabama, 36535, United States

Location

Site US117 - Valley Pain Consultants

Scottsdale, Arizona, 85254, United States

Location

Site US116 - Arizona Pain Specialists

Scottsdale, Arizona, 85258, United States

Location

Site US124 - Quality of Life Medical and Research Centers LLC

Tucson, Arizona, 85712, United States

Location

Site US154 - Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Site US110 - Orange County Research Institute

Anaheim, California, 92801, United States

Location

Site US172 - Core Healthcare Group

Cerritos, California, 90703, United States

Location

Site US108 - Catalina Research Institute

Chino, California, 91710, United States

Location

Site US175 - Inland Pain Medicine

Colton, California, 92324, United States

Location

Site US152 - UC San Diego Healthcare Systems, Center for Pain Medicine

La Jolla, California, 92093, United States

Location

Site US102 - Samaritan Center for Medical Research

Los Gatos, California, 95032, United States

Location

Site US126 - Northern California Research

Sacramento, California, 95821, United States

Location

Site US106 - Mountain View Clinical Research

Denver, Colorado, 80209, United States

Location

Site US153 - Clinical Research of West Florida Inc - Clearwater

Clearwater, Florida, 33765, United States

Location

Site US162 - South Lake Pain Institute

Clermont, Florida, 34711, United States

Location

Site US143 - Florida Pain Institute

Merritt Island, Florida, 32953, United States

Location

Site US111 - Sunrise Research Institute

Miami, Florida, 33130, United States

Location

Site US122 - Precision Research Organization, LLC

Miami Lakes, Florida, 33016, United States

Location

Site US104 - Discovery Clinical Trials

Orlando, Florida, 32806, United States

Location

Site US133 - Gold Coast Research LLC

Plantation, Florida, 33317, United States

Location

Site US171 - Florida Medical Pain Management

St. Petersburg, Florida, 33709, United States

Location

Site US121 - Clinical Research of West Florida

Tampa, Florida, 33603, United States

Location

Site US165 - Palm Beach Research

West Palm Beach, Florida, 33409, United States

Location

Site US131 - Better Health Clinical Research, Inc

Newnan, Georgia, 30265, United States

Location

Site US103 - Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Site US129 - International Clinical Research Institute

Overland Park, Kansas, 66210, United States

Location

Site US169 - Massachusetts General Hospital

Boston, Massachusetts, 01773, United States

Location

Site US127 - Advance Clinical Research, Inc

St Louis, Missouri, 63128, United States

Location

Site US105 - Advanced Biomedical Research of America

Las Vegas, Nevada, 89123, United States

Location

Site US101 - Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Site US151 - Premier Pain Centers

Shrewsbury, New Jersey, 07702, United States

Location

Site US156 - University Clinical Research Center

Somerset, New Jersey, 08502, United States

Location

Site US166 - Albany Medical College

Albany, New York, 12208, United States

Location

Site US145 - University of Rochester

Rochester, New York, 14618, United States

Location

Site US137 - Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Site US135 - The Center for Clinical Research

Winston-Salem, North Carolina, 27103, United States

Location

Site US157 - North Star Medical Research

Middleburg Heights, Ohio, 44130, United States

Location

Site US149 - Founders Research Corporation

Philadelphia, Pennsylvania, 19152, United States

Location

Site US114 - Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Site US112 - Clinical Trials of South Carolina

Charleston, South Carolina, 29406, United States

Location

Site US107 - Austin Center for Clinical Research

Austin, Texas, 78756, United States

Location

Site US134 - Lovelace Scientific Resources, Inc

Austin, Texas, 78758, United States

Location

Site US113 - Pioneer Research Solutions, Inc

Houston, Texas, 77099, United States

Location

Site US118 - Omega International Pain Clinic

Salt Lake City, Utah, 84106, United States

Location

Site US164 - Advanced Clinical Research

West Jordan, Utah, 84088, United States

Location

Site US144 - Bellevue Surgery Center

Bellevue, Washington, 98004, United States

Location

Site US173 - Bellevue Surgery Center

Bellevue, Washington, 98004, United States

Location

Site US123 - Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Site US161 - Swedish Pain and Headache Center

Seattle, Washington, 98104, United States

Location

Site DE107 - Studienzentrum A. Schwittay

Böhlen, 04564, Germany

Location

Site DE104 - Schmerzzentrum Dr. med. C. Wachter & T. Tusker

Fellbach, 70736, Germany

Location

Site DE101 - Klinische Forschung Hannover Mitte GmbH

Hanover, 30159, Germany

Location

Site DE103 - Algesiologikum Studienzentrum und Algesiologikum MVZ

Munich, 80799, Germany

Location

Site DE102 - Universitätsklinikum Würzburg Neurologische Klinik

Würzburg, 97080, Germany

Location

Site GB104 - The Royal Victoria Infirmary

Cambridge, NE1 4LP, United Kingdom

Location

Site GB108 - Darlington Memorial Hospital, Centre for Research and clinical Intervention

Darlington, DL3 6HX, United Kingdom

Location

Site GB109 - Royal Devon Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Site GB101 - Guys and St. Thomas NHS Foundation Trust - St Thomas Hospital

London, SE1 7EH, United Kingdom

Location

Site GB111 - Chelsea and Westminster Hospital - NHS Foundation Trust

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

Reflex Sympathetic Dystrophy

Interventions

6-amino-1-hydroxyhexane-1,1-diphosphonate

Condition Hierarchy (Ancestors)

Complex Regional Pain Syndromes; Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: March 30, 2015
• Study Start: April 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: November 1, 2016
• Last Updated: May 9, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

US (49); GB (5); DE (5)