Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease.

INTRODUCTION: KW-6356 is a novel selective adenosine A2A receptor antagonist/inverse agonist. We evaluated the efficacy and safety of KW-6356 as monotherapy in patients with early, untreated Parkinson's disease (PD). METHODS: This was a randomized, placebo-controlled, double-blind study conducted in Japan to investigate the efficacy and safety of once-daily KW-6356 (3 or 6 mg/day) orally administered as monotherapy for 12 weeks in patients with early PD (NCT02939391). The primary endpoint was the least squares means of change from baseline in the MDS-UPDRS Part III total score. RESULTS: Overall, 168 patients were randomized and treated (KW-6356 3 mg/day n = 55; 6 mg/day n = 58, placebo n = 55); Week 12 completion rates were >90% per group. LS mean [95% CI] changes from baseline to Week 12 in MDS-UPDRS Part III total scores were -5.37 [-7.25, -3.48] for 3 mg/day, -4.76 [-6.55, -2.96] for 6 mg/day and -3.14 [-4.97, -1.30] for placebo. Changes from baseline were larger for both KW-6356 groups than for the placebo group at all time points. Secondary endpoints supported the primary findings with larger changes in MDS-UPDRS Part II, Parts II + III, and Total scores in the KW-6356 groups than in the placebo group. Treatment was well-tolerated; the most common treatment-emergent adverse events with KW-6356 were constipation (n = 4 [7.3%] and n = 6 [10.3%] in the 3 and 6 mg/day groups, respectively) followed by nasopharyngitis (n = 4 [7.3%] and n = 5 [8.6%] in the 3 and 6 mg/day groups, respectively). CONCLUSION: KW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD.