Clinical trial NCT04006210: 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
Official title: A Multicenter, Randomized, Active-controlled, Double-blind, Double-dummy, Parallel-group Clinical Trial, Investigating the Efficacy, Safety, and Tolerability of Continuous Subcutaneous ND0612 Infusion in Comparison to Oral IR-LD/CD in Subjects With Parkinson's Disease Experiencing Motor Fluctuations (BouNDless)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: NeuroDerm Ltd.
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 381
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Oral IR-LD/CD Adjustment Period - Run-in 1 (1 arm) followed by ND0612 Conversion Period - Run-in 2 (1 arm) followed by DBDD Parallel Group Maintenance Period (2 arms) followed by optional Open-label Extension Period (1 arm)
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients, aged ≥30 years.
2. PD diagnosis consistent with the United Kingdom Brain Bank Criteria.
3. Modiﬁed Hoehn \& Yahr score ≤3 during "ON" state.
4. 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.
5. 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.

Exclusion Criteria:

1. Atypical or secondary parkinsonism.
2. Severe disabling dyskinesias, based on Investigator's discretion.
3. Previous neurosurgery for PD.
4. Use of duodenal levodopa infusion (LCIG) or apomorphine infusion.
5. Use of the following medications: subcutaneous apomorphine injections, sublingual apomorphine, or inhaled levodopa within 4 weeks.
6. Previous participation in ND0612 studies.
7. History of signiﬁcant skin conditions or disorders.

Primary outcomes:
measure: The change in daily ON time without troublesome dyskinesia
timeFrame: Baseline to the end of DBDD Maintenance Period (12 weeks)
Secondary outcomes:
measure: The change in daily OFF time
timeFrame: Baseline to the end of DBDD Maintenance Period (12 weeks)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Cedar- Sinai Medical Center Department of Neurology
state: California
city: Reseda
country: United States
facility: SC3 Research - Reseda
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center
state: Colorado
city: Vernon
country: United States
facility: Hartford Healthcare Chase Family Movement Disorders Center
state: Connecticut
city: Aventura
country: United States
facility: Visionary Investigators Network
state: Florida
city: Boca Raton
country: United States
facility: Parkinsons Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: University of Florida Norman Fixel Institute for Neurological Diseases
state: Florida
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center
state: Florida
city: Winter Park
country: United States
facility: Neurology One
state: Florida
city: Atlanta
country: United States
facility: Emory University - Brain Health Center
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Des Moines
country: United States
facility: Unity Point Health
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Neurology and Movement Disorder
state: Kentucky
city: New Orleans
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai Medical center Movement Disorders Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates LTD.
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Neurology Consultants of Dallas
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Madison
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: La Louvière
country: Belgium
facility: CHU de Tivoli
city: Brno
country: Czechia
facility: Neurologicka klinika Fakutni nemocnice sv. Anny v Brne
city: Praha 5
country: Czechia
facility: Axon Clinical s.r.o.
city: Bron
country: France
facility: Hopital Neurologique
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied
city: Nantes
country: France
facility: CHU Nantes-Hopital Laennec
city: Nice
country: France
facility: CHU de Nice Hpital Pasteur
city: Nimes
country: France
facility: Chu Caremeau
city: Toulouse
country: France
facility: Hopital Purpan
city: Pécs
country: Hungary
facility: University of Pecs, Clinical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Ein Kerem
city: Nahariya
country: Israel
facility: Galilee Medical center- Nahariya
city: Petah Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Arcugnano
country: Italy
facility: Casa di Cura Villa Margherita
city: Cassino
country: Italy
facility: Centro Ricerca Parkinson San Raffaele Cassino
city: Chieti
country: Italy
facility: University Chieti CeSI MET Clinical research center-CRC
city: Grosseto
country: Italy
facility: Ospedale di Grosseto, Azienda USL Toscana Sud Est
city: Milano
country: Italy
facility: Istituto Clinico Humanitas - IRCCS
city: Naples
country: Italy
facility: AOU University of Campania "Luigi Vanvitelli"
city: Pavia
country: Italy
facility: IRCCS Fondazione C. Mondino
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
city: Rome
country: Italy
facility: Policlinico Tor Vergata - UOSD Parkinson
city: Rome
country: Italy
facility: IRCCS Santa Lucia Foundation
city: Amsterdam
country: Netherlands
facility: University of Amsterdam
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o. o
city: Lodz
country: Poland
facility: NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki
city: Siemianowice Śląskie
country: Poland
facility: Neuro-Care SP z o. o.
city: Warsaw
country: Poland
facility: Oddział Neurologii ul. L. Kondratowicza 8
city: Braga
country: Portugal
facility: Hospital Braga
city: Torres Vedras
country: Portugal
facility: CNS - Campus Neurologico Senior
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Krasnoyarsk
country: Russian Federation
facility: Federal Siberian Scientic Clinical Center of FMBA
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk regional specialized scientific-practical neurological center on the basis City Clinical Hospital 34
city: St. Petersburg
country: Russian Federation
facility: The first Saint-Petersburg State Medical University named after IP Pavlov
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Bratislava
country: Slovakia
facility: Nemocnica akad. L. Derera
city: Kosice
country: Slovakia
facility: Univerzitna nemocnica L. Pasteura Kosice
city: Oviedo
country: Spain
facility: Hospital Universitario central de Asturias
state: Asturias
city: Alicante
country: Spain
facility: Hospital General Universitario de Elche, Edificio principal
city: Barcelona
country: Spain
facility: Hospital Universitari de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari General de Catalunya
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Madrid
country: Spain
facility: Complejo Hospitalario Ruber Juan Bravo
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío, Laboratorio 104.
city: Valencia
country: Spain
facility: Hospital Universitario y Politcnico de La Fe
city: Kyiv
country: Ukraine
facility: Clinic "Dopomoga Plus"
city: Kyiv
country: Ukraine
facility: Institute of Gerontolgoy - Parkinsons disease Treatment Centre
city: Poltava
country: Ukraine
facility: Ukrainian Medical Stomatological Academy based on Poltava Regional Clinical Hospital n.a. M.V.Skliphosovskyy
city: Vinnytsia
country: Ukraine
facility: Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital
city: Zaporozhye
country: Ukraine
facility: Municipal Non-commercial Institution '' City hospital #9" of Zaporizhzhya City Council
city: London
country: United Kingdom
facility: King's College hospital
city: London
country: United Kingdom
facility: St Georges University Hospital
city: London
country: United Kingdom
facility: Directorate of Medicine & Integrated Care, Imperial College Healthcare NHS Trust
city: Newcastle
country: United Kingdom
facility: Clinical Ageing research Unit
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
affiliation: University of Cincinnati OH, USA
name: Alberto J Espay, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Toulouse University Hospital, France
name: Olivier Rascol, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: