Abstract Details

Title Impact of 24-hour Subcutaneous Levodopa/Carbidopa Infusion (ND0612) on Motor Function: Efficacy Outcomes from the Phase 3 BouNDless Study

Topic Movement Disorders

Presentation(s) S37 - Movement Disorders: Clinical Trials (1:00 PM-1:12 PM)

Poster/Presentation
Number 001

Background

Primary efficacy analysis demonstrated superiority of ND0612 over immediate-release levodopa/carbidopa (IR-LD/CD), with a difference of 1.72h (p<0.0001) in Good ON-time.

Objective

To evaluate the effect of investigational ND0612 on PD motor state characteristics in patients with PD experiencing motor fluctuations from the BouNDless (NCT04006210) study.

Design/Methods

We performed post hoc analysis of diary data and descriptively analyzed the number and duration of episodes spent in each PD motor state. The total number of transitions between any motor state were analyzed by baseline-adjusted Poisson Regression. Patients who completed the double-blind phase of the study were eligible to enter into the ND0612 OLE (up to 54 months). Changes in diary states (from ND0612 initiation in the run-in phase) were normalized to 16h and analyzed using mixed model repeated measures without imputation.

Results

At the end of the double-blind phase, patients in the ND0612 vs IR-LD/CD group experienced an average of 2.4 vs 3.3 OFF episodes per day, with a total daily OFF-duration of 3.8h vs 5.2h. Participants (ND0612 vs IR-LD/CD) experienced 2.7 vs 3.1 episodes of ON without dyskinesia (total duration of 9.4h vs 7.4h); 1.2 vs 1.4 episodes of ON with non-troublesome dyskinesia (total duration of 2.2h vs 2.7h); and 0.3 vs 0.5 episodes of ON with troublesome dyskinesia (total duration of 0.4h vs 0.7h). The mean number of daily transitions between motor states (ND0612 vs IR-LD/CD) was 5.3 vs 7.1 (p<0.0001). Most (167/232; 72%) participants who entered the OLE, completed 1 year of ND0612 treatment. Efficacy benefits were sustained at Month 12 with a change of –1.86±0.18h in OFF-time (P<0.0001), +1.96±0.18h in Good ON-time, and +2.19±0.26h in ON-time without any dyskinesia. The ND0612 regimen was generally safe and well-tolerated.

Conclusions

Treatment with ND0612, versus IR-LD/CD, led to more stable motor control in patients with PD and motor fluctuations.

Authors/Disclosures
Rajesh Pahwa, MD, FAAN (University of Kansas Medical Center) PRESENTER	Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Photopharmics. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Neuroderm. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Blue Rock. The institution of Dr. Pahwa has received research support from Cerevance. The institution of Dr. Pahwa has received research support from Fasikl. The institution of Dr. Pahwa has received research support from Scion. The institution of Dr. Pahwa has received research support from UCB. The institution of Dr. Pahwa has received research support from Ono. The institution of Dr. Pahwa has received research support from Intra-cellular Therapies. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Michael J Fox Foundation . The institution of Dr. Pahwa has received research support from Neuron 23. The institution of Dr. Pahwa has received research support from Roche.
Aaron Ellenbogen, DO	Dr. Ellenbogen has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for allergan. Dr. Ellenbogen has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for allergan. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for ipsen. Dr. Ellenbogen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda.
Alberto J. Espay, MD, FAAN (University of Cincinnati)	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.
Robert A. Hauser, MD, MBA, FAAN (Movement Disorders Center)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Kinetics Consulting (GKC). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa Kirin Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDerm. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion Neurostim LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tolmar Inc.. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Revance Therapeutics. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus Pharma. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Pharma 2 B. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vivifi Biotech. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ovid Therapeutics. Dr. Hauser has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Amneal. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AgeX Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avanex. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BlueRock Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MDCE Suzhou. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PDNeurotechnology. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Regenxbio. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Tremor Research Support Group. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tris Pharma. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Canfield Scientific. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Forsee Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KiefeRx. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Intrance. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zambon. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Truebinding. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Serina Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nano PharmaSolutions. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HanAll. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. The institution of Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoparkinson. The institution of Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Photopharmics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Amneal . Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Neurocrine. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Cerevel. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Inhibikase. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. Dr. Hauser has stock in Inhibikase. Dr. Hauser has stock in Axial Therapeutics. Dr. Hauser has stock in Enterin. Dr. Hauser has stock in Revance Therapeutics. The institution of Dr. Hauser has received research support from Annovis Bio, Inc.. The institution of Dr. Hauser has received research support from Inhibikase Therapeutics. The institution of Dr. Hauser has received research support from AbbVie, Inc.. The institution of Dr. Hauser has received research support from Aeon Biopharma. The institution of Dr. Hauser has received research support from Biogen MA. The institution of Dr. Hauser has received research support from Bukwang Pharmaceutical Co., Ltd.. The institution of Dr. Hauser has received research support from Cavion, Inc.. The institution of Dr. Hauser has received research support from Cerevance Beta, Inc.. The institution of Dr. Hauser has received research support from Cerevel Therapeutics. The institution of Dr. Hauser has received research support from Enterin, Inc.. The institution of Dr. Hauser has received research support from Genentech. The institution of Dr. Hauser has received research support from Global Kinetics Corporation. The institution of Dr. Hauser has received research support from Hoffman-La Roche Inc. The institution of Dr. Hauser has received research support from Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Hauser has received research support from National Parkinson's Foundation. The institution of Dr. Hauser has received research support from Neuraly Inc.. The institution of Dr. Hauser has received research support from Neuroderm. The institution of Dr. Hauser has received research support from Sage Therapeutics. The institution of Dr. Hauser has received research support from Sanofi Pharmaceuticals. The institution of Dr. Hauser has received research support from Scion NeuroStim. The institution of Dr. Hauser has received research support from UCB BioPharma. The institution of Dr. Hauser has received research support from UCB. The institution of Dr. Hauser has received research support from MJFF. The institution of Dr. Hauser has received research support from Biogen. The institution of Dr. Hauser has received research support from Alexza Pharmaceuticals. Dr. Hauser has received intellectual property interests from a discovery or technology relating to health care.
Fabrizio Stocchi	Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bial, Biogen, Sunovion, Lundbeck, UCB, Zambon, Chiesi, Lusofarmaco, Abbvie, Neuroderm, Kyowa, Synegile, Roche, Britannia, Sunovion, Blue Rock. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIAL, Zambon, Biogen, Roche, Synegile, Sunovion. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial, Zambon, UCB, Kyowa, Sunovion.
Joaquim J. Ferreira	The institution of Joaquim J. Ferreira has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bial, Neurocrine, AbbVie, Biogen and Lundbeck. The institution of Joaquim J. Ferreira has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine, AbbVie, BIAL, Biogen, Lundbeck . The institution of Joaquim J. Ferreira has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie, BIAL, Nordic Infucare, ONO and SK Chemicals.
Karl D. Kieburtz, MD (University of Rochester Medical Center)	Dr. Kieburtz has received personal compensation for serving as an employee of Clintrex Research Corporation. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Kieburtz has stock in Clintrex Research Corp. Dr. Kieburtz has stock in Hoover Brown. An immediate family member of Dr. Kieburtz has stock in Hoover Brown. Dr. Kieburtz has stock in Safe Therapeutics. The institution of Dr. Kieburtz has received research support from NIH. The institution of Dr. Kieburtz has received research support from Michae J Fox Foundation.
Alberto Albanese, MD (Universita Cattolica Sacro Cuore)	Dr. Albanese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ipsen pharma. Dr. Albanese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merz pharms. Dr. Albanese has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Publishing Group. Dr. Albanese has a non-compensated relationship as a President with International Association on Parkinsonism and Related Disorders that is relevant to AAN interests or activities.
Nir Giladi, MD, FAAN (Tel-Aviv Medical Center)	Dr. Giladi has received personal compensation in the range of $0-$499 for serving as a Consultant for Sionara. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharma2B. Dr. Giladi has stock in Vibrant. Dr. Giladi has stock in Lysosomal Therapeutics . The institution of Dr. Giladi has received research support from The Michael J Fox Foundation. The institution of Dr. Giladi has received research support from The National Parkinson Foundation. The institution of Dr. Giladi has received research support from The European Union . The institution of Dr. Giladi has received research support from The Israel Science Foundation. The institution of Dr. Giladi has received research support from Biogen . The institution of Dr. Giladi has received research support from Ionis. The institution of Dr. Giladi has received research support from Sieratzki Family Foundation . The institution of Dr. Giladi has received research support from The Aufzien Academic Center in Tel-Aviv University.
Laurence Salin	Laurence Salin has received personal compensation for serving as an employee of NeuroDerm.
Nissim Sasson, Sr.	Mr. Sasson has nothing to disclose.
Liat Adar (Neuroderm)	Liat Adar has received personal compensation for serving as an employee of Neuroderm.
Natalia Vostokova, PhD	Ms. Vostokova has received personal compensation for serving as an employee of NeuroDerm Ltd.
Jonathan Pereira, MD	Mr. Pereira has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma America.
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).

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