ND0612H: Preliminary Ph IIa Trial 006 data

Preliminary data from the observer-blind, international Phase IIa Trial 006 in 38 advanced PD patients showed that continuous 24-hour treatment with ND0612H met the primary endpoint of reducing daily “off” time vs. baseline (2.7 vs. 5.5 hours, p=0.004). Patients received continuous 24-hour treatment with 720/90 mg ND0612H levodopa/carbidopa at a high day rate for 18 hours and a low night rate for 6 hours, or a morning dose of 150/15 mg oral levodopa/carbidopa followed by continuous treatment with 538/68 mg ND0612H levodopa/carbidopa over 14 waking hours. Patients could add oral levodopa/carbidopa as needed. The 14-hour regimen missed the primary endpoint (non-significant reduction of 1.3 hours compared to baseline). The 24-hour regimen also met the secondary endpoint of improving the proportion of patients self-reporting a first “on” period vs. baseline by 8:00 AM (50% vs. 11%, p=0.02) and 9:00 AM (75% vs. 26%, p=0.004). NeuroDerm said there was no improvement from baseline at either time point in the 14-hour cohort, as dosing began in the morning. The 24-hour (12.9 vs. 9.2 hours, p<0.001) and 14-hour (11.3 vs. 8.5 hours, p=0.003) regimens both met the secondary endpoint of improving daily “good on” time vs. baseline. A “good on” period was defined as an “on” period with no or mild dyskinesia.

Complete elimination of “off” time occurred in 42% and 11% of patients receiving the 24- and 14-hour regimens, respectively. ND0612H led to a response, defined any reduction in “off” time, in 68% of patients, including 12 patients in the 24-hour arm and 14 patients in the 14-hour arm. Complete elimination of “off” time occurred in 66% of 24-hour responders and 14% of 14-hour responders. The 24-hour regimen reduced “off” time by >50% in all responders. The 24- and 14-hour regimens reduced Unified Parkinson’s Disease Rating Scale (UPDRS) III scores from baseline by 8:00 AM to 18.3 points from 37.4 (p<0.001) and to 26.6 points from 37.3 (p=0.001), respectively. In patients from both arms with >1 hours of troublesome dyskinesia at baseline (n=14), ND0612H reduced “on” time with observer-assessed moderate or severe dyskinesia to 1.6 hours from a baseline of 5.1 hours (p=0.011). Patients reduced average oral levodopa dose level and frequency from about 1,100 mg levodopa 6.6 times daily at baseline to about 330 mg levodopa 2.3 times daily by day 28. The candidate was generally well tolerated, with infusion site reactions reported as the most common adverse event...