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Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial
- Source :
- Osteoarthritis and cartilage. 28(1)
- Publication Year :
- 2019
-
Abstract
- Summary Objective CR4056 is a selective imidazoline-2 (I2) receptor ligand with potent analgesic activity in animal pain models. This proof-of-concept study tested CR4056 efficacy and safety in patients with knee osteoarthritis (OA) and different phenotypes. Design This is a multicenter, randomized, double-blind, placebo-controlled trial. Knee OA patients with moderate to severe pain received CR4056 (women 100 mg bid; men 200 mg bid) or placebo (both genders) for 14 days. The primary outcome was the change in WOMAC pain score (0–100 scale) compared to placebo, analyzed in the intention-to-treat population and pre-defined OA phenotypes. Results 213 patients were treated with CR4056 (92 women; 52 men) or placebo (69 overall). After 14 days, median WOMAC pain improvements were 10 points on placebo and 14, 20 and 16 in women, men, and pooled CR4056 groups (P = 0.184, 0.030 and 0.070 vs placebo, respectively). Pre-specified subgroup analysis in the metabolic OA phenotype (BMI ≥ 27.5 kg/m2, N = 156) showed statistically significant differences in all CR4056-treated groups vs placebo of 12–18 points. Conversely, there were too few patients with a neuropathic or inflammatory phenotype for a meaningful analysis. CR4056 was well tolerated; the most common adverse event was mild headache. Conclusions Although the primary endpoint was met in males only, this exploratory phase 2 trial shows that CR4056 might be an effective analgesic against knee OA pain, especially in overweight patients representing the metabolic OA phenotype. These findings, along with the broad-spectrum analgesic activity of CR4056 in animal models, warrant further clinical investigation in OA and other pain conditions. Clinical trial registration number EudraCT 2015-001136-37.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
WOMAC
Population
Analgesic
Biomedical Engineering
Osteoarthritis
Placebo
Proof of Concept Study
law.invention
03 medical and health sciences
0302 clinical medicine
Rheumatology
Randomized controlled trial
Double-Blind Method
law
Internal medicine
medicine
Clinical endpoint
Humans
Orthopedics and Sports Medicine
education
Pain Measurement
030203 arthritis & rheumatology
education.field_of_study
business.industry
Imidazoles
Middle Aged
Osteoarthritis, Knee
medicine.disease
Arthralgia
Clinical trial
030104 developmental biology
Treatment Outcome
Quinazolines
Female
business
Subjects
Details
- ISSN :
- 15229653
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Osteoarthritis and cartilage
- Accession number :
- edsair.doi.dedup.....5ac709b6c7e5b3230365e9f7ced3e16f