MedPath

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

Phase 3
Active, not recruiting
Conditions
Parkinson's Disease
Interventions
Combination Product: Placebo for SC infusion
Drug: Oral IR-LD/CD
Combination Product: ND0612 Solution for SC infusion
Drug: 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
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.
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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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IR-LD/CD GroupPlacebo for SC infusionPlacebo 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 AdjustmentOral IR-LD/CDActive IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks.
ND0612 GroupOral IR-LD/CDND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 GroupPlacebo for Oral IR-LD/CDND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 ConversionND0612 Solution for SC infusionND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.
IR-LD/CD GroupPlacebo for Oral IR-LD/CDPlacebo 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 GroupOral IR-LD/CDPlacebo 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 GroupND0612 Solution for SC infusionND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 ConversionOral IR-LD/CDND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.
Open-Label ExtensionND0612 Solution for SC infusionND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months.
Primary Outcome Measures
NameTimeMethod
The change in daily ON time without troublesome dyskinesiaBaseline 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
NameTimeMethod
The change in daily OFF timeBaseline 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

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