The aim of this trial was to investigate the safety of intravenous neridronic acid in patients with complex regional pain syndrome (CRPS). The trial was 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).
At the Enrollment Visit the trial objectives, procedures, and risks were explained to the participants and the informed consent form was signed. Medical history was obtained, a physical examination was conducted, and other safety assessments were performed. Signs and symptoms of CRPS were assessed to confirm the diagnosis of CRPS according to the Budapest clinical criteria. Participants were trained to report their pain. Calcium and vitamin D supplementation were initiated to ensure sufficient vitamin D levels prior to treatment. Participants meeting all eligibility criteria received infusions of investigational medicinal product (IMP) during visits on Day 1, Day 4, Day 7, and Day 10. Flexibility of ±1 day was allowed for Day 4, Day 7, and Day 10 whilst ensuring a minimum period of 48 hours between infusions. During the treatment period and follow-up period, pain intensity ratings were captured at the site visits in a patient reported-outcome system.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
580
Neridronic acid administered as intravenous infusion.
Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)
The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.
Time frame: Day 1 to Week 52
Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event
The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.
Time frame: Day 1 to Day 10
Change From Baseline in the Current Pain Intensity Score
The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine", a higher score indicates more pain.
Time frame: Baseline to Week 12 and Week 26
Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score
Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.
Time frame: Baseline, at Week 12 and Week 26
Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score
Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.
Time frame: Baseline, at Week 12 and Week 26
Patient Global Impression of Change (PGIC) at Week 12
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US017: Cactus Clinical Research, Inc.
Phoenix, Arizona, United States
US028: Quality of Life Medical and Research Centers LLC
Tucson, Arizona, United States
US045: Woodland International Research Group
Little Rock, Arkansas, United States
US044: Woodland Research Northwest
Rogers, Arkansas, United States
US012: Orange County Research Institute
Anaheim, California, United States
US022: Core Healthcare Group
Cerritos, California, United States
US033: Alliance Research Centers
Laguna Hills, California, United States
US027: The Helm Center for Pain Management
Laguna Woods, California, United States
US003: Samaritan Center for Medical Research
Los Gatos, California, United States
US010: Catalina Research Institute, LLC
Montclair, California, United States
...and 36 more locations
The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected 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 improvement.
Time frame: at Week 12
Patient Global Impression of Change (PGIC) at Week 26
The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected 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 improvement.
Time frame: at Week 26
Change in the Pain Interference Score of the Brief Pain Inventory (BPI)
The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated 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.
Time frame: Baseline to Week 12 and Week 26