Efficacy and safety of subcutaneous L-dopa/carbidopa (ND0612H) infusion in fluctuating PD patients (S26.003)

Objective: Evaluate the efficacy and safety of two dosing regimens of continuous subcutaneous L-dopa/carbidopa (ND0612H).Background: ND0612 is a proprietary levodopa/carbidopa (LD/CD) liquid solution designed for continuous subcutaneous infusion.Design/Methods: This was a 28-day randomized, parallel-group, open-label, blinded-rater study. Subjects with fluctuating PD were randomized to either: Regimen-1 (24h infusion with 720/90mg LD/CD) or Regimen-2 (14h ‘waking-day’ infusion with 538/68mg LD/CD + morning oral LD/CD 150/15mg). Supplemental oral LD/CD was used as needed. Primary endpoint: Change from baseline to Day 28 in daily OFF-time (blinded rater standard 8h observation normalized to 16h day). Key Secondary endpoints included Change from baseline in percent of subjects with full-ON at 8 & 9 AM.Results: Of the 38 randomized subjects (mean age: 63.5y; disease duration: 11.5y; mean OFF-time 5.3h/day), 33 (87%) completed the study. Regimen-1 met the primary endpoint (mean reduction in OFF-time of 2.8h, p=0.004); 8 of 19 (42%) subjects had a complete reduction in OFF-time to 0 hours. The proportion of subjects with full-ON was significantly increased at 8AM (p=0.02) and 9AM (p=0.007). ‘Good’ ON-time also increased (mean 3.7h; p<0.001). In Regimen-2, mean reduction in OFF time was 1.3h (NS) and ‘good’ ON-time increased by 2.8h (p=0.003). Both regimens were well-tolerated; the most frequent AEs were mild-moderate infusion-site reactions: nodules (47%), bruising (18%) and erythema (18%).Conclusions: Both regimens were well-tolerated. The 24h infusion significantly reduced daily OFF-time while increasing morning ON-time and total daily good ON-time. R2 did not provide optimal dosing for ND0612 but still showed a significant improvement in good ON-time. A longer daytime regimen of 16h (LD/CD 720/90 mg) starting immediately upon waking up is under evaluation. These findings suggest that ND0612 SC infusion can provide important benefits for advanced PD patients without the risks associated with a surgical procedure.Study Supported by: NeuroDermDisclosure: Dr. Olanow has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant to AbbVie, Addex, Lundbeck, Newron, Novartis, Teva, and Zambon. Owns stock in Clintrex which provides consulting services for Acorda, AstraZeneca,Biotie, Cynapsus, EMD Serono, Dart Neuroscience, Jazz, Knopp, Kyowa Kirin, Lundbeck, Melior Discov. Dr. Stocchi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NeuroDerm, GlaxoSmithKline, Boehringer Ingelheim, Britannia, Lundbeck, Orion Novartis, Teva, Newron, Merck Serono, and Pfizer. Dr. Poewe has nothing to disclose. Dr. Ellenbogen has nothing to disclose. Dr. Djaldetti has nothing to disclose. Dr. Rahmilevich has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NeuroDerm. Dr. Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NeuroDerm. Dr. Oren has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NeuroDerm. Dr. Kieburtz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Research grants from the National Institutes of Health, the Michael J. Fox Foundation, Medivation, and Neurosearch. Consultant to the United States Food and Drug Administration, Veterans Administration, and National Institutes of Health, AbbVie, Acorda, A.