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Trial record 8 of 835 for:    crps | Open Studies

Safety of Intravenous Neridronic Acid in CRPS

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Grünenthal GmbH
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT02972359
First received: November 21, 2016
Last updated: March 13, 2017
Last verified: March 2017
  Purpose

The aim of this trial is to investigate the safety of intravenous neridronic acid in patients with complex regional pain syndrome (CRPS).

The trial is divided into 3 periods: a 60-day enrollment period, a treatment period consisting of 4 infusions over 10 days, and a follow-up period of approximately 50 weeks (with visits at Week 2, Week 6, Week 12, Week 26, Week 39, and Week 52).


Condition Intervention Phase
Complex Regional Pain Syndrome
Drug: Neridronic acid
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Open-label Safety Trial of Intravenous Neridronic Acid in Subjects With Complex Regional Pain Syndrome (CRPS)

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Occurrence of any treatment emergent adverse event [ Time Frame: Day 1 to Week 52 ]
    The primary endpoint of this trial is a binary endpoint assessing whether or not a subject experienced any TEAE.


Secondary Outcome Measures:
  • Occurrence of permanent discontinuation from treatment due to an adverse event. [ Time Frame: Day 1 to Day 10 ]
  • Change from baseline in the current pain intensity score [ Time Frame: Baseline to Week 12 and Week 26 ]
    The current CRPS-related pain intensity score will be captured at each visit using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine".

  • Response to treatment, defined as at least 30% decrease from baseline in the current pain intensity score. [ Time Frame: Baseline, at Week 12 and Week 26 ]
    Participants with at least a 30 percent decrease in the current pain intensity score will be considered to have responded to treatment.

  • Response to treatment, defined as at least 50% decrease from baseline in the current pain intensity score. [ Time Frame: Baseline, at Week 12 and Week 26 ]
    Participants with at least a 50 percent decrease in the current pain intensity score will be considered to have responded to treatment.

  • Patient Global Impression of Change (PGIC) [ Time Frame: at Week 12 ]
    The PGIC is a self-reported measure of perceived change in overall condition since the start of the study. Participants will select one of seven responses ranging from very much improved to very much worse. A response of very much improved or much improved is generally regarded as a clinically important outcome.

  • Patient Global Impression of Change (PGIC) [ Time Frame: at Week 26 ]
    The PGIC is a self-reported measure of perceived change in overall condition since the start of the study. Participants will select one of seven responses ranging from very much improved to very much worse. A response of very much improved or much improved is generally regarded as a clinically important outcome.

  • Change in the Pain Interference score of the Brief Pain Inventory (BPI). [ Time Frame: Baseline to Week 12 and Week 26 ]
    The BPI Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants will rate their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.


Estimated Enrollment: 220
Study Start Date: December 2016
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neridronic acid
Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.
Drug: Neridronic acid
Neridronic acid administered as intravenous infusion.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent signed.
  • Male or female participant at least 18 years of age at Visit 1.
  • A diagnosis of complex regional pain syndrome according to the clinical diagnostic criteria recommended by the International Association for the Study of Pain (IASP; "Budapest clinical criteria"), assessed at Visit 1. Signs and symptoms of CRPS must apply to an affected limb (arm or leg) and must demonstrate asymmetry with respect to the contralateral limb.
  • Ongoing moderate to severe chronic pain, including a baseline current pain intensity score of greater than or equal to 4 using an 11-point Numerical Rating Scale referring to the CRPS-affected limb, at Visit 2 (prior to dosing).
  • In stable treatment and follow-up therapy for CRPS for at least 1 month prior to allocation to treatment (Visit 2).
  • Women of child-bearing potential must have a negative urine beta-human chorionic gonadotropin (β-HCG) pregnancy test at Visit 1 and must be using 2 forms of medically acceptable contraception, including at least 1 highly effective method of contraception with a low failure rate, defined as less than 1% per year (e.g., oral contraceptives or intrauterine device), and a second medically acceptable method such as use of condoms with spermicide by their male partner. A barrier method alone is not acceptable. Highly effective methods of contraception must be used for at least 2 months prior to Visit 2 and for the duration of 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 (assistance in filling out the questionnaires may be provided, if required due to motor or other impairment).

Exclusion Criteria:

  • Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2 using the 2009 Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation [Levey et al. 2009] or a urinary albumin creatinine ratio greater than 30 mg/g), based on central safety laboratory data, or a history of chronic kidney disease. Note: If 2 consecutive laboratory tests indicate eGFR levels greater than 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.
  • Serum calcium or magnesium outside of the central laboratory's reference range, based on central safety laboratory data obtained prior to Visit 2 (a single repeat laboratory test is allowed); a history of hypocalcemia or a metabolic disorder anticipated to increase risk for hypocalcemia (e.g., hypoparathyroidism); concomitant use of drug(s) with known potential to cause hypocalcemia (e.g., aminoglycosides).
  • Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL, based on central safety laboratory data obtained prior to Visit 2 (a single repeat laboratory test is allowed). Participants with vitamin D deficiency should receive appropriate supplementation during the enrollment period. A normal vitamin D level (greater than or equal to 30 ng/mL) must be documented prior to allocation to investigational medicinal product (IMP).
  • Corrected QT interval (according to Fridericia's formula; QTcF) greater than 470 ms (average of 3 electrocardiograms [ECGs] obtained at Visit 1); serum potassium outside the central laboratory's reference range at Visit 1; clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or an indwelling pacemaker; 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.
  • Participants receiving medications with a known risk of torsades de pointes within 7 days prior to allocation. Participants receiving selective serotonin re-uptake inhibitor antidepressants (e.g., citalopram, escitalopram) 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.
  • 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 drugs affecting bone turnover or bone metabolism within 6 months prior to Visit 1.
  • History of any allergic or hypersensitivity reaction to neridronic acid or other bisphosphonate, acetaminophen, or to vitamin D or calcium supplements.
  • Recent tooth extraction or other invasive dental procedure (within 3 months prior to Visit 1), unhealed or infected extraction site, or significant dental/periodontal disease (e.g., impacted molars, severe tooth decay, foci of infection) that may predispose to need for tooth extraction or other invasive dental procedures during the trial. Participants with indeterminate, suspicious or unreliable dental history, in the opinion of the investigator, must undergo a dental examination prior to receiving treatment.
  • Evidence of denture-related gum trauma or improperly fitting dentures causing injury.
  • Prior radiation therapy of the head or neck (within 1 year of Visit 1).
  • History of malignancy within 2 years prior to Visit 1, with the exception of basal cell carcinoma.
  • 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.
  • Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within 2 years of Visit 1, 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.
  • Women who are pregnant or breastfeeding.
  • Elevated aspartate aminotransferase or alanine aminotransferase greater than 2-fold upper limit of normal, based on central safety laboratory data obtained at Visit 1, or current evidence of chronic liver disease. Safety laboratory testing may be repeated prior to Visit 2, and participants will be allowed in the trial if results of 2 consecutive tests, at least 3 days apart, are less than or equal to 2-fold upper limit of normal.
  • Participation in another investigational drug trial within 3 months prior to Visit 1 or any previous trial with neridronic acid, with the exception of participants of KF7013-01 who were assigned to placebo and did not receive neridronic acid.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02972359

Contacts
Contact: Patient Recruitment Service +001 855-598-9992 Clinical-Trials@grunenthal.com

  Show 37 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Study Director: Study Director Grünenthal GmbH
  More Information

Additional Information:
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT02972359     History of Changes
Other Study ID Numbers: KF7013-03
2016-001164-11 ( EudraCT Number )
U1111-1180-8099 ( Other Identifier: World Health Organization )
Study First Received: November 21, 2016
Last Updated: March 13, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description:

Details available at:

http://www.grunenthal.com/grt-web/Grunenthal_Group/Research_Development/Grunenthal_Clinical_Trials/Data_Sharing/296200025.jsp


Keywords provided by Grünenthal GmbH:
Neridronic Acid
Neridronate
CRPS
RSD (reflex sympathetic dystrophy)

Additional relevant MeSH terms:
Complex Regional Pain Syndromes
Syndrome
Reflex Sympathetic Dystrophy
Disease
Pathologic Processes
Autonomic Nervous System Diseases
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 22, 2017