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

NCT04006210 | Active Not Recruiting Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: ND0612-317
• Study Type: interventional
• Target: 381
• Locations: 16 countries
• Sites: 103

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• The change in daily ON time without troublesome dyskinesia

  ON time without troublesome dyskinesia is the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia per patient diary

  Baseline to the end of DBDD Maintenance Period (12 weeks)

Secondary Outcomes (1)

• The change in daily OFF time

  Baseline to the end of DBDD Maintenance Period (12 weeks)

Study Arms (5)

ND0612 Group

EXPERIMENTAL

ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.

Combination Product: ND0612 Solution for SC infusion; Drug: Oral IR-LD/CD; Drug: Placebo for Oral IR-LD/CD

IR-LD/CD Group

ACTIVE COMPARATOR

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.

Combination Product: Placebo for SC infusion; Drug: Oral IR-LD/CD; Drug: Placebo for Oral IR-LD/CD

Oral IR-LD/CD Adjustment

OTHER

Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks.

Drug: Oral IR-LD/CD

ND0612 Conversion

OTHER

ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.

Combination Product: ND0612 Solution for SC infusion; Drug: Oral IR-LD/CD

Open-Label Extension

OTHER

ND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months.

Combination Product: ND0612 Solution for SC infusion

Interventions

ND0612 Solution for SC infusion COMBINATION_PRODUCT

Levodopa/Carbidopa (LD/CD) solution administered SC via infusion pump

ND0612 Conversion; ND0612 Group; Open-Label Extension

Placebo for SC infusion COMBINATION_PRODUCT

Placebo solution administered SC via infusion pump

IR-LD/CD Group

Oral IR-LD/CD DRUG

Encapsulated LD/CD 100mg/25mg

Also known as: IR-LD/CD

IR-LD/CD Group; ND0612 Conversion; ND0612 Group; Oral IR-LD/CD Adjustment

Placebo for Oral IR-LD/CD DRUG

Encapsulated Placebo for LD/CD 100mg/25mg

Also known as: Placebo for IR-LD/CD

IR-LD/CD Group; ND0612 Group

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NeuroDerm Ltd.: lead

Study Sites (103)

Xenoscience

Phoenix, Arizona, 85004, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Cedar- Sinai Medical Center Department of Neurology

Los Angeles, California, 90048 -1804, United States

Location

SC3 Research - Reseda

Reseda, California, 91335, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

Hartford Healthcare Chase Family Movement Disorders Center

Vernon, Connecticut, 06066, United States

Location

Visionary Investigators Network

Aventura, Florida, 33180, United States

Location

Parkinsons Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486-2359, United States

Location

University of Florida Norman Fixel Institute for Neurological Diseases

Gainesville, Florida, 32608, United States

Location

Neurology Associates PA

Maitland, Florida, 32751-4723, United States

Location

USF Parkinson's Disease and Movement Disorders Center

Tampa, Florida, 33613, United States

Location

Neurology One

Winter Park, Florida, 32792, United States

Location

Emory University - Brain Health Center

Atlanta, Georgia, 30329, United States

Location

NeuroStudies

Decatur, Georgia, 30033, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Unity Point Health

Des Moines, Iowa, 50309, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky, Neurology and Movement Disorder

Lexington, Kentucky, 40536-0284, United States

Location

Oschner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334-2980, United States

Location

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Mount Sinai Medical center Movement Disorders Center

New York, New York, 10029, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, Pennsylvania, 19101-4511, United States

Location

Abington Neurological Associates LTD.

Willow Grove, Pennsylvania, 19090-1749, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Neurology Consultants of Dallas

Dallas, Texas, 75243, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia

Charlottesville, Virginia, 22908-0816, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53705-2281, United States

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

CHU de Tivoli

La Louvière, 7100, Belgium

Location

Neurologicka klinika Fakutni nemocnice sv. Anny v Brne

Brno, 65691, Czechia

Location

Axon Clinical s.r.o.

Prague, 150 00, Czechia

Location

Hopital Neurologique

Bron, 69677, France

Location

Hopital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

CHU Nantes-Hopital Laennec

Nantes, 44800, France

Location

CHU de Nice Hpital Pasteur

Nice, 6002, France

Location

Chu Caremeau

Nîmes, GARD 30000, France

Location

Hopital Purpan

Toulouse, 31059, France

Location

University of Pecs, Clinical Center

Pécs, 7623, Hungary

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center, Ein Kerem

Jerusalem, 9112001, Israel

Location

Galilee Medical center- Nahariya

Nahariya, 22100, Israel

Location

Rabin Medical Center, Beilinson Hospital

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Casa di Cura Villa Margherita

Arcugnano, 36057, Italy

Location

Centro Ricerca Parkinson San Raffaele Cassino

Cassino, 03043, Italy

Location

University Chieti CeSI MET Clinical research center-CRC

Chieti, 66100, Italy

Location

Ospedale di Grosseto, Azienda USL Toscana Sud Est

Grosseto, 58100, Italy

Location

Istituto Clinico Humanitas - IRCCS

Milan, 20089, Italy

Location

AOU University of Campania "Luigi Vanvitelli"

Naples, 80138, Italy

Location

IRCCS Fondazione C. Mondino

Pavia, 27100, Italy

Location

IRCCS San Raffaele Pisana

Roma, RM 163, Italy

Location

Policlinico Tor Vergata - UOSD Parkinson

Rome, 00133, Italy

Location

IRCCS Santa Lucia Foundation

Rome, 179, Italy

Location

University of Amsterdam

Amsterdam, 1105, Netherlands

Location

Krakowska Akademia Neurologii Sp. z o. o

Krakow, 31-505, Poland

Location

NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki

Lodz, 90-640, Poland

Location

Neuro-Care SP z o. o.

Siemianowice Śląskie, 41-100, Poland

Location

Oddział Neurologii ul. L. Kondratowicza 8

Warsaw, 03-242, Poland

Location

Hospital Braga

Braga, 4710-243, Portugal

Location

CNS - Campus Neurologico Senior

Torres Vedras, 256-280, Portugal

Location

Kazan State Medical University

Kazan', 420012, Russia

Location

Federal Siberian Scientic Clinical Center of FMBA

Krasnoyarsk, 660037, Russia

Location

Novosibirsk regional specialized scientific-practical neurological center on the basis City Clinical Hospital 34

Novosibirsk, 630054, Russia

Location

The first Saint-Petersburg State Medical University named after IP Pavlov

Saint Petersburg, 197022, Russia

Location

Siberian State Medical University

Tomsk, 634050, Russia

Location

Nemocnica akad. L. Derera

Bratislava, 833 05, Slovakia

Location

Univerzitna nemocnica L. Pasteura Kosice

Košice, 04166, Slovakia

Location

Hospital Universitario central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital General Universitario de Elche, Edificio principal

Alicante, 03203, Spain

Location

Hospital Universitari de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari General de Catalunya

Barcelona, 08195, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Complejo Hospitalario Ruber Juan Bravo

Madrid, 28006, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Infanta Sofia

Madrid, 28702, Spain

Location

Hospital Universitario Virgen del Rocío, Laboratorio 104.

Seville, 41013, Spain

Location

Hospital Universitario y Politcnico de La Fe

Valencia, 46026, Spain

Location

Clinic "Dopomoga Plus"

Kyiv, 04111, Ukraine

Location

Institute of Gerontolgoy - Parkinsons disease Treatment Centre

Kyiv, 4114, Ukraine

Location

Ukrainian Medical Stomatological Academy based on Poltava Regional Clinical Hospital n.a. M.V.Skliphosovskyy

Poltava, 36011, Ukraine

Location

Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital

Vinnytsia, 21005, Ukraine

Location

Municipal Non-commercial Institution '' City hospital #9" of Zaporizhzhya City Council

Zaporizhzhya, 69065, Ukraine

Location

King's College hospital

London, SE5 9RT, United Kingdom

Location

St Georges University Hospital

London, SW17 0QT, United Kingdom

Location

Directorate of Medicine & Integrated Care, Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Clinical Ageing research Unit

Newcastle, NE4 5PL, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, PL6 5FP, United Kingdom

Location

Related Publications (1)

• Espay AJ, Stocchi F, Pahwa R, Albanese A, Ellenbogen A, Ferreira JJ, Giladi N, Gurevich T, Hassin-Baer S, Hernandez-Vara J, Isaacson SH, Kieburtz K, LeWitt PA, Lopez-Manzanares L, Olanow CW, Poewe W, Sarva H, Yardeni T, Adar L, Salin L, Lopes N, Sasson N, Case R, Rascol O; BouNDless Study Group. Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial. Lancet Neurol. 2024 May;23(5):465-476. doi: 10.1016/S1474-4422(24)00052-8. Epub 2024 Mar 15.

  PMID: 38499015 DERIVED

Related Links

• European Union Clinical Trials Register

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Alberto J Espay, MD, MSc

  University of Cincinnati OH, USA

  PRINCIPAL INVESTIGATOR

• Olivier Rascol, MD, PhD

  Toulouse University Hospital, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded Site Rater, Blinded Clinical Research Associates (CRAs), active drugs and matching placebos are identical in their appearances.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: June 30, 2019
• First Posted: July 5, 2019
• Study Start: September 30, 2019
• Primary Completion: November 1, 2022
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

AU (1); FR (6); IL (6); BE (1); GB (5); UA (5); NL (1); IT (10); HU (1); PL (4); RU (5); PT (2); US (38); CZ (2); ES (14); SL (2)