HONOLULU, HI— “Significant, clinically meaningful improvements in spontaneous bowel movement (SBM) frequency were observed after CB-5945 treatment,” stated Lee Techner, DPM, from Cubist Pharmaceuticals, Lexington, MA, at the American Pain Society’s 31st Annual Scientific Meeting.
Mu opioid receptor (MOR) binding and to some extent delta opioid receptor (DOR) binding play a role in opioid-induced constipation (OIC) and gastrointestinal (GI) symptoms. CB-5945, a MOR and DOR antagonist, is currently being developed for OIC and associated abdominal symptoms in patients on chronic opioid therapy for persistent noncancer pain.
Dr. Techner and colleagues conducted two Phase 2, randomized, double-blind, placebo-controlled studies that compared CB-5945 0.1mg twice daily (n= 43), 0.25mg twice daily (n= 45), and 0.25mg once daily (n=40) dosing with placebo (n=43 [twice daily] and n=41[once daily]) to assess SBM change over four weeks. Other study endpoints included overall SBM responders (patient with ≥3 SBM/week and ≥1 SBM/week from baseline for 3 of 4 weeks), opioid consumption, pain scores, and adverse events.
Mean OIC duration of the study population ranged from 3.4–6.9 years and back pain was the most common pain condition. Data showed mean SBM changes from baseline with CB-5945 to be 4.62 (0.25mg twice daily), 3.39 (0.25mg once daily), and 3.11 (0.1mg twice daily) compared with 1.4 for both placebo groups with a mean treatment difference change of 1.98 (P=0.0003), 1.18 (P=0.0118), and 0.51 (P=0.2979), in the 0.25mg twice daily, 0.25mg once daily, and 0.1mg twice daily groups, respectively. Overall response was seen in 56% (0.25mg twice daily; P=0.0052), 43% (0.25mg once daily), and 28% (0.1mg twice daily) of patients compared with 26–29% of patients in the placebo cohorts. There were no changes in opioid consumption or pain scores and no evidence of CNS effects.
The most commonly reported adverse events were abdominal pain (once daily regimen; 10% across groups) and upper respiratory tract infection (twice daily regimen; placebo, 14%; 0.1mg, 7%; 0.25mg, 7%). GI-related adverse events were mostly mild in severity and incidence was low and comparable across all groups.
Based on the results, Dr. Techner and colleagues concluded that the 0.25mg twice daily dose demonstrated the most favorable benefit-to-risk profile. They further added that Phase 3 trials are planned for the future.