Efficacy and tolerability of a selective α2C‐adrenergic receptor blocker in recovery from cold‐induced vasospasm in scleroderma patients: A single‐center, double‐blind, placebo‐controlled, randomized crossover study

Abstract

Objective OPC‐28326 is a selective α‐adrenergic antagonist with preferential binding to the α_2C‐adrenergic receptor (α_2C‐AR) subtype. This study observed the effect of OPC‐28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma. Methods The study was designed as a single‐center, double‐blind, placebo‐controlled, randomized, 3‐period crossover study of OPC‐28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature. Results Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC‐28326 40‐mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC‐28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC‐28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug‐related were reported more frequently with 40 mg OPC‐28326 than with 10 mg OPC‐28326 or with placebo, but none were serious or sustained. Conclusion OPC‐28326 at doses of 10 mg and 40 mg was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC‐28326 suggests that selective α_2C‐AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.