Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis

摘要

Introduction/Aims Long-term efficacy and safety of dichlorphenamide (DCP) were characterized in patients with primary periodic paralysis (PPP). Methods Patients with PPP in a double-blind, placebo-controlled study were randomly assigned to receive DCP 50 mg twice daily or placebo for 9 weeks, followed by a 52-week open-label DCP treatment phase (DCP/DCP and placebo/DCP populations). Efficacy (attack rate, severity-weighted attack rate) and safety were assessed in patients completing the study (61 weeks). In this post hoc analysis, efficacy and safety data were pooled from hyperkalemic and hypokalemic substudies. Results Sixty-three adults (age, 19-76 years) completed the double-blind phase; 47 (74.6) of these patients completed 61 weeks. There were median decreases in weekly attack and severity-weighted attack rates from baseline to week 61 (DCP/DCP n = 25, -1.00 P < .0001; placebo/DCP n = 20, -0.63 P = .01 and DCP/DCP, -2.25 P < .0001; placebo/DCP, -1.69 P = .01). Relatively smaller median decreases in weekly attack and severity-weighted attack rates occurred from weeks 9 to 61 among patients receiving DCP continuously (n = 26; -0.14 P = .1 and -0.24 P = .09) than among those switching from placebo to DCP after 9 weeks (n = 16; -1.04 P = .049 and -2.72 P = .08). Common adverse events (AEs) were paresthesia and cognition-related events, which typically first occurred within 1 month of blinded treatment initiation and in rare cases led to treatment discontinuation. Dose reductions were frequently associated with common AE resolution. Discussion One-year open-label DCP treatment after a 9-week randomized, controlled study confirmed long-term DCP remains safe and effective for chronic use. Tolerability issues (paresthesia, cognition-related AEs) were manageable in most patients.