Efficacy, Safety and Tolerability Study of ND0612 vs. Oral Immediate Release Levodopa/Carbidopa (IR-LD/CD) in Subjects With Parkinson's Disease Experiencing Motor Fluctuations
- Conditions
- Parkinson's Disease
- Interventions
- Combination Product: Placebo for SC infusionDrug: Oral IR-LD/CDCombination Product: ND0612 Solution for SC infusionDrug: Placebo for Oral IR-LD/CD
- Registration Number
- NCT04006210
- Lead Sponsor
- NeuroDerm Ltd.
- Brief Summary
This is a multi-center, randomized, double-blind, double-dummy, active controlled clinical Study. Following a screening period, eligible subjects will be enrolled to an open-label oral IR-LD/CD adjustment period; then an open-label ND0612 conversion period; then after optimization periods subjects will be randomized to receive either ND0612 or its matching Placebo with IR-LD/CD.
Subjects can continue to an optional open-label extension period.
- Detailed Description
This is a phase III multi-center, randomized, active-controlled, double-blind, double-dummy (DBDD), parallel group clinical trial, investigating the efficacy, safety, and tolerability of continuous subcutaneous (SC) ND0612 infusion in comparison to oral IR-LD/CD in subjects with Parkinson's disease (PD) experiencing motor fluctuations.
This study is comprised of 6 periods:
1. a Screening Period;
2. an open-label oral IR-LD/CD Adjustment Period;
3. an open-label ND0612 Conversion Period;
4. a randomized DBDD active-controlled Maintenance Period;
5. an optional open-label Treatment Extension; and
6. a Safety Follow-up Period.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 381
- Male and female patients, aged ≥30 years.
- PD diagnosis consistent with the United Kingdom Brain Bank Criteria.
- Modified Hoehn & Yahr score ≤3 during "ON" state.
- Average of ≥2.5 hours of OFF time (≥2 hours "OFF" time every day) during waking hours as confirmed by patient diary over 3 days.
- Taking ≥4 levodopa doses/day (≥3 doses/day of extended release LD/dopa-decarboxylase inhibitor, e.g., Rytary®) at a total daily dose of ≥400mg.
- Atypical or secondary parkinsonism.
- Severe disabling dyskinesias, based on Investigator's discretion.
- Previous neurosurgery for PD.
- Use of duodenal levodopa infusion (LCIG) or apomorphine infusion.
- Use of the following medications: subcutaneous apomorphine injections, sublingual apomorphine, or inhaled levodopa within 4 weeks.
- Previous participation in ND0612 studies.
- History of significant skin conditions or disorders.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IR-LD/CD Group Placebo for SC infusion Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. Oral IR-LD/CD Adjustment Oral IR-LD/CD Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks. ND0612 Group Oral IR-LD/CD ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. ND0612 Group Placebo for Oral IR-LD/CD ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. ND0612 Conversion ND0612 Solution for SC infusion ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks. IR-LD/CD Group Placebo for Oral IR-LD/CD Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. IR-LD/CD Group Oral IR-LD/CD Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. ND0612 Group ND0612 Solution for SC infusion ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. ND0612 Conversion Oral IR-LD/CD ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks. Open-Label Extension ND0612 Solution for SC infusion ND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months.
- Primary Outcome Measures
Name Time Method The change in daily ON time without troublesome dyskinesia Baseline to the end of DBDD Maintenance Period (12 weeks) ON time without troublesome dyskinesia is the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia per patient diary
- Secondary Outcome Measures
Name Time Method The change in daily OFF time Baseline to the end of DBDD Maintenance Period (12 weeks) OFF time per patient diary
Trial Locations
- Locations (103)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Rocky Mountain Movement Disorders Center
🇺🇸Englewood, Colorado, United States
Visionary Investigators Network
🇺🇸Aventura, Florida, United States
Parkinsons Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Hospital Universitario central de Asturias
🇪🇸Oviedo, Asturias, Spain
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Hopital Purpan
🇫🇷Toulouse, France
Univerzitna nemocnica L. Pasteura Kosice
🇸🇰Kosice, Slovakia
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Oschner Medical Center
🇺🇸New Orleans, Louisiana, United States
IRCCS Santa Lucia Foundation
🇮🇹Rome, Italy
Siberian State Medical University
🇷🇺Tomsk, Russian Federation
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Ospedale di Grosseto, Azienda USL Toscana Sud Est
🇮🇹Grosseto, Italy
Xenoscience
🇺🇸Phoenix, Arizona, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
Galilee Medical center- Nahariya
🇮🇱Nahariya, Israel
CHU de Tivoli
🇧🇪La Louvière, Belgium
Hadassah Medical Center, Ein Kerem
🇮🇱Jerusalem, Israel
CNS - Campus Neurologico Senior
🇵🇹Torres Vedras, Portugal
Medical University Innsbruck
🇦🇹Innsbruck, Austria
University of Pecs, Clinical Center
🇭🇺Pécs, Hungary
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Federal Siberian Scientic Clinical Center of FMBA
🇷🇺Krasnoyarsk, Russian Federation
QUEST Research Institute
🇺🇸Farmington Hills, Michigan, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Kazan State Medical University
🇷🇺Kazan, Russian Federation
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Novosibirsk regional specialized scientific-practical neurological center on the basis City Clinical Hospital 34
🇷🇺Novosibirsk, Russian Federation
The first Saint-Petersburg State Medical University named after IP Pavlov
🇷🇺St. Petersburg, Russian Federation
Clinic "Dopomoga Plus"
🇺🇦Kyiv, Ukraine
Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital
🇺🇦Vinnytsia, Ukraine
Nemocnica akad. L. Derera
🇸🇰Bratislava, Slovakia
Ukrainian Medical Stomatological Academy based on Poltava Regional Clinical Hospital n.a. M.V.Skliphosovskyy
🇺🇦Poltava, Ukraine
Municipal Non-commercial Institution '' City hospital #9" of Zaporizhzhya City Council
🇺🇦Zaporozhye, Ukraine
University of California San Francisco
🇺🇸San Francisco, California, United States
Duke University
🇺🇸Durham, North Carolina, United States
Cedar- Sinai Medical Center Department of Neurology
🇺🇸Los Angeles, California, United States
SC3 Research - Reseda
🇺🇸Reseda, California, United States
Hartford Healthcare Chase Family Movement Disorders Center
🇺🇸Vernon, Connecticut, United States
Emory University - Brain Health Center
🇺🇸Atlanta, Georgia, United States
Neurology Associates PA
🇺🇸Maitland, Florida, United States
Neurology One
🇺🇸Winter Park, Florida, United States
NeuroStudies
🇺🇸Decatur, Georgia, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Mount Sinai Medical center Movement Disorders Center
🇺🇸New York, New York, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Neurology Consultants of Dallas
🇺🇸Dallas, Texas, United States
Abington Neurological Associates LTD.
🇺🇸Willow Grove, Pennsylvania, United States
Neurologicka klinika Fakutni nemocnice sv. Anny v Brne
🇨🇿Brno, Czechia
Axon Clinical s.r.o.
🇨🇿Praha 5, Czechia
Hopital Neurologique
🇫🇷Bron, France
Hopital Gabriel Montpied
🇫🇷Clermont-Ferrand, France
CHU Nantes-Hopital Laennec
🇫🇷Nantes, France
CHU de Nice Hpital Pasteur
🇫🇷Nice, France
Chu Caremeau
🇫🇷Nimes, France
Rabin Medical Center, Beilinson Hospital
🇮🇱Petah Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Casa di Cura Villa Margherita
🇮🇹Arcugnano, Italy
Centro Ricerca Parkinson San Raffaele Cassino
🇮🇹Cassino, Italy
University Chieti CeSI MET Clinical research center-CRC
🇮🇹Chieti, Italy
Istituto Clinico Humanitas - IRCCS
🇮🇹Milano, Italy
AOU University of Campania "Luigi Vanvitelli"
🇮🇹Naples, Italy
Krakowska Akademia Neurologii Sp. z o. o
🇵🇱Krakow, Poland
Policlinico Tor Vergata - UOSD Parkinson
🇮🇹Rome, Italy
IRCCS San Raffaele Pisana
🇮🇹Roma, Italy
IRCCS Fondazione C. Mondino
🇮🇹Pavia, Italy
NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki
🇵🇱Lodz, Poland
University of Amsterdam
🇳🇱Amsterdam, Netherlands
Oddział Neurologii ul. L. Kondratowicza 8
🇵🇱Warsaw, Poland
Neuro-Care SP z o. o.
🇵🇱Siemianowice Śląskie, Poland
Hospital Braga
🇵🇹Braga, Portugal
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario de Elche, Edificio principal
🇪🇸Alicante, Spain
Hospital Universitari de la Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Hospital Universitari General de Catalunya
🇪🇸Barcelona, Spain
Complejo Hospitalario Ruber Juan Bravo
🇪🇸Madrid, Spain
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Infanta Sofia
🇪🇸Madrid, Spain
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocío, Laboratorio 104.
🇪🇸Sevilla, Spain
Hospital Universitario y Politcnico de La Fe
🇪🇸Valencia, Spain
Institute of Gerontolgoy - Parkinsons disease Treatment Centre
🇺🇦Kyiv, Ukraine
King's College hospital
🇬🇧London, United Kingdom
Directorate of Medicine & Integrated Care, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
St Georges University Hospital
🇬🇧London, United Kingdom
Clinical Ageing research Unit
🇬🇧Newcastle, United Kingdom
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Corporal Michael J. Crescenz VA Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
University of Florida Norman Fixel Institute for Neurological Diseases
🇺🇸Gainesville, Florida, United States
USF Parkinson's Disease and Movement Disorders Center
🇺🇸Tampa, Florida, United States
Unity Point Health
🇺🇸Des Moines, Iowa, United States
University of Kentucky, Neurology and Movement Disorder
🇺🇸Lexington, Kentucky, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Wisconsin Madison
🇺🇸Madison, Wisconsin, United States