Evaluate efficacy of 2 dosing ND0612 regimens (R1: 24h infusion & R2: 14h daytime infusion) on early morning OFF (EMO) and nocturnal symptoms in fluctuating PD. 

Nocturnal symptoms and EMO periods are significant contributors to poor quality of life in patients with Parkinson’s disease experiencing motor fluctuations. ND0612 is a L-dopa/carbidopa (LD/CD) solution continuously administered via subcutaneous infusion. Primary results from this Phase-2 study showed reductions in total daily OFF time from baseline (R1: -2.8h, p=0.004 and R2: -1.3h, p=0.158).

After 1 day of standard oral LD/CD treatment, 38 subjects with fluctuating PD (mean age: 63.5y; OFF-time 5.3h/day) were randomized to 2 ND0612 dosing regimens for 28 days: R1 (total LD/CD dose: 720/90 mg) or R2 (total dose: 538/68mg+ 1 morning dose of oral LD/CD [150/15 mg]). 

In R1, the proportion of subjects with full ON at 8AM increased from 11% at baseline to 50% at Day 28 (p=0.02) and at 9AM from 32% to 75% (p=0.007). Early morning UPDRS motor scores improved from 37.4 at baseline to 20.3 at Day 28 (mean [95%CI] improvement of -19.1 [-25.6, -12.5] points, p<0.0001); mean PDSS-2 scores also significantly improved from baseline to Day 27 (-4.1 [-8.0, -0.2]; p=0.042). Treatment initiation was delayed in R2 until a nurse started the pump and thus no improvement in in the proportion of patients with full ON was seen at 8 or 9 AM. While waking day dosing (R2) had no significant effect on sleep quality, 8 AM UPDRS motor scores significantly improved by -10.7 [-16.8, -4.6] points (p=0.001).

24h LD infusion with ND0612 significantly increased morning ON-time with relevant improvement in motor status. Sleep quality also improved, indicating that patients benefited from the pump overnight. ND0612 may provide a minimally invasive option of continuous LD delivery for PD patients experiencing nocturnal and early morning motor fluctuations.