Abstract Details

Title The BouNDless Study: An Active-Controlled, Randomized, Double-Blind, Double-Dummy Phase 3 Study of Continuous ND0612 Infusion in Patients with Parkinson’s Disease Experiencing Motor Fluctuations

Topic Movement Disorders

Presentation(s) P9 - Poster Session 9 (12:00 PM-1:00 PM)

Poster/Presentation
Number 3-003

Objective To evaluate the safety and efficacy of ND0612 versus active control in patients with Parkinson disease.

Background ND0612 is under development as a non-surgical drug-device combination to provide continuous subcutaneous delivery of levodopa/carbidopa for patients with Parkinson’s disease (PD) and motor fluctuations.

Design/Methods This phase 3 study (NCT04006210) will enroll 288 PD patients (Hoehn and Yahr ≤3) on ≥4 doses/day of oral LD/CD therapy and experiencing motor fluctuations (≥2.5 hours OFF daily, with ≥2 hours OFF during waking hours). The study comprises 6 periods: Period-1: Screening (1-4 weeks); Period-2: Open-label oral CD/LD optimization period (6 weeks); Period-3: Open-label ND0612 optimization period (6 weeks); Period-4: Double-blind, double-dummy, active-controlled, maintenance period where patients are randomized to either ND0612 infusion + Dummy IR LD/CD, OR to Dummy infusion + IR LD/CD (12 weeks); Period-5: Optional open-label extension period (1-year); Period-6: Safety follow-up (12 weeks).

Results Primary endpoint: Change from Baseline (start of ND0612 infusion) to end of the maintenance period in mean ON time without troublesome dyskinesia, normalized to 16 waking hours, using patient-rated ON/OFF diary assessments. Secondary outcome measures include changes in: OFF time (key secondary), UPDRS (Parts II and III), Patient’s and Clinician’s Global Impressions of Change, ON time without dyskinesia, PDQ-39 and Parkinson’s Disease Sleep Scale (PDSS) scores. Clinical assessments are by blinded-rater. Safety and tolerability are assessed via adverse event reporting, including local skin safety assessments, rates of premature discontinuation, and study treatment compliance.

Conclusions Subcutaneous infusion of levodopa may provide a well-tolerated and convenient route of continuous levodopa delivery. However, poor levodopa solubility has, until now, precluded this approach. BouNDless is the first phase 3 randomized, active-controlled trial designed to evaluate the efficacy and safety of treatment with continuous subcutaneous ND0612 in comparison to oral immediate-release LD/CD in patients with PD experiencing motor fluctuations.

Authors/Disclosures
Alberto J. Espay, MD, F�鶹��ýӳ�� (University of Cincinnati) PRESENTER	Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Tanabe Pharma America (formerly, Neuroderm). Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Herantis Pharma. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus (formerly USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaps Dx. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bial. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDiagnostics, Inc (SYNAPS Dx). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Intrance Medical Systems, Inc.. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Praxis Precision Medicines. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Citrus Health. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. The institution of Dr. Espay has received research support from NIH. The institution of Dr. Espay has received research support from Michael J Fox Foundation for Parkinson's Research. Dr. Espay has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care.
Olivier Rascol, MD, PhD (Departments of Clinical Pharmacology and Neurosciences-CIC9302/INSERM 825)	Dr. Rascol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie, Acorda, Aguettant, Alkahest, AlzProtect, Apopharma, Astrazeneca, Axovant, Bial, Biogen, Britannia, Buckwang, Centogene, Cerevel, Clevexel, Contera, GE Healthcare, Handltherapeutic, Ionis, Irlab, Jazz, Kyowa, LGD Nuvamid, Lundbeck, Merck, Merz, MundiPharma, Neuralight, Neuratris, Neuroderm, Novartis, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Parexel, PD Neurotechnology, Pfizer, Polycaps, Prexton, Roche Therapeutics, Sanofi, Scienture, Servier,Sombiotech, Sunovion, Supernus, Synagile, Thelonius Mind, Takeda, Théranexus, Teva, Tools4patient, UCB, Vision 2 voice, XenoPort, XO, Zambon . Dr. Rascol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie, Acorda, Aguettant, Alkahest, AlzProtect, Apopharma, Astrazeneca, Axovant, Bial, Biogen, Britannia, Buckwang, Centogene, Cerevel, Clevexel, Contera, GE Healthcare, Handltherapeutic, Ionis, Irlab, Jazz, Kyowa, LGD Nuvamid, Lundbeck, Merck, Merz, MundiPharma, Neuralight, Neuratris, Neuroderm, Novartis, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Parexel, PD Neurotechnology, Pfizer, Polycaps, Prexton, Roche Therapeutics, Sanofi, Scienture, Servier,Sombiotech, Sunovion, Supernus, Synagile, Thelonius Mind, Takeda, Théranexus, Teva, Tools4patient, UCB, Vision 2 voice, XenoPort, XO, Zambon . Dr. Rascol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIAL. Dr. Rascol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MEDIZIN ACADEMY. The institution of Dr. Rascol has received research support from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020).
Tamar Yardeni	Tamar Yardeni has received personal compensation for serving as an employee of Neuroderm.
	No disclosure on file
	No disclosure on file
Ryan J. Case, PhD	Dr. Case has received personal compensation for serving as an employee of NeuroDerm.
C. W. Olanow, MD	Dr. Olanow has received personal compensation for serving as an employee of Clintrex Research Corporation. Dr. Olanow has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Clintrex Research Corporation. Dr. Olanow has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Chevron/Syngenta. Dr. Olanow has stock in Clintrex Research Corporation.

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