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

NCT ID: NCT04006210

Last Updated: 2025-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

381 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-30

Study Completion Date

2027-02-28

Brief Summary

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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

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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.

Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Blinded Site Rater, Blinded Clinical Research Associates (CRAs), active drugs and matching placebos are identical in their appearances.

Study Groups

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ND0612 Group

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

Group Type EXPERIMENTAL

ND0612 Solution for SC infusion

Intervention Type COMBINATION_PRODUCT

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

Oral IR-LD/CD

Intervention Type DRUG

Encapsulated LD/CD 100mg/25mg

Placebo for Oral IR-LD/CD

Intervention Type DRUG

Encapsulated Placebo for LD/CD 100mg/25mg

IR-LD/CD Group

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.

Group Type ACTIVE_COMPARATOR

Placebo for SC infusion

Intervention Type COMBINATION_PRODUCT

Placebo solution administered SC via infusion pump

Oral IR-LD/CD

Intervention Type DRUG

Encapsulated LD/CD 100mg/25mg

Placebo for Oral IR-LD/CD

Intervention Type DRUG

Encapsulated Placebo for LD/CD 100mg/25mg

Oral IR-LD/CD Adjustment

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

Group Type OTHER

Oral IR-LD/CD

Intervention Type DRUG

Encapsulated LD/CD 100mg/25mg

ND0612 Conversion

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

Group Type OTHER

ND0612 Solution for SC infusion

Intervention Type COMBINATION_PRODUCT

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

Oral IR-LD/CD

Intervention Type DRUG

Encapsulated LD/CD 100mg/25mg

Open-Label Extension

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

Group Type OTHER

ND0612 Solution for SC infusion

Intervention Type COMBINATION_PRODUCT

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

Interventions

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ND0612 Solution for SC infusion

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

Intervention Type COMBINATION_PRODUCT

Placebo for SC infusion

Placebo solution administered SC via infusion pump

Intervention Type COMBINATION_PRODUCT

Oral IR-LD/CD

Encapsulated LD/CD 100mg/25mg

Intervention Type DRUG

Placebo for Oral IR-LD/CD

Encapsulated Placebo for LD/CD 100mg/25mg

Intervention Type DRUG

Other Intervention Names

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IR-LD/CD Placebo for IR-LD/CD

Eligibility Criteria

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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.
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NeuroDerm Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alberto J Espay, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati OH, USA

Olivier Rascol, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Toulouse University Hospital, France

Locations

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Xenoscience

Phoenix, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Cedar- Sinai Medical Center Department of Neurology

Los Angeles, California, United States

Site Status

SC3 Research - Reseda

Reseda, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

Site Status

Hartford Healthcare Chase Family Movement Disorders Center

Vernon, Connecticut, United States

Site Status

Visionary Investigators Network

Aventura, Florida, United States

Site Status

Parkinsons Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Site Status

University of Florida Norman Fixel Institute for Neurological Diseases

Gainesville, Florida, United States

Site Status

Neurology Associates PA

Maitland, Florida, United States

Site Status

USF Parkinson's Disease and Movement Disorders Center

Tampa, Florida, United States

Site Status

Neurology One

Winter Park, Florida, United States

Site Status

Emory University - Brain Health Center

Atlanta, Georgia, United States

Site Status

NeuroStudies

Decatur, Georgia, United States

Site Status

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Unity Point Health

Des Moines, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky, Neurology and Movement Disorder

Lexington, Kentucky, United States

Site Status

Oschner Medical Center

New Orleans, Louisiana, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Michigan State University

East Lansing, Michigan, United States

Site Status

QUEST Research Institute

Farmington Hills, Michigan, United States

Site Status

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, United States

Site Status

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Mount Sinai Medical center Movement Disorders Center

New York, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Abington Neurological Associates LTD.

Willow Grove, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Neurology Consultants of Dallas

Dallas, Texas, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

University of Wisconsin Madison

Madison, Wisconsin, United States

Site Status

Medical University Innsbruck

Innsbruck, , Austria

Site Status

CHU de Tivoli

La Louvière, , Belgium

Site Status

Neurologicka klinika Fakutni nemocnice sv. Anny v Brne

Brno, , Czechia

Site Status

Axon Clinical s.r.o.

Prague, , Czechia

Site Status

Hopital Neurologique

Bron, , France

Site Status

Hopital Gabriel Montpied

Clermont-Ferrand, , France

Site Status

CHU Nantes-Hopital Laennec

Nantes, , France

Site Status

CHU de Nice Hpital Pasteur

Nice, , France

Site Status

Chu Caremeau

Nîmes, , France

Site Status

Hopital Purpan

Toulouse, , France

Site Status

University of Pecs, Clinical Center

Pécs, , Hungary

Site Status

Shaare Zedek Medical Center

Jerusalem, , Israel

Site Status

Hadassah Medical Center, Ein Kerem

Jerusalem, , Israel

Site Status

Galilee Medical center- Nahariya

Nahariya, , Israel

Site Status

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Casa di Cura Villa Margherita

Arcugnano, , Italy

Site Status

Centro Ricerca Parkinson San Raffaele Cassino

Cassino, , Italy

Site Status

University Chieti CeSI MET Clinical research center-CRC

Chieti, , Italy

Site Status

Ospedale di Grosseto, Azienda USL Toscana Sud Est

Grosseto, , Italy

Site Status

Istituto Clinico Humanitas - IRCCS

Milan, , Italy

Site Status

AOU University of Campania "Luigi Vanvitelli"

Naples, , Italy

Site Status

IRCCS Fondazione C. Mondino

Pavia, , Italy

Site Status

IRCCS San Raffaele Pisana

Roma, , Italy

Site Status

Policlinico Tor Vergata - UOSD Parkinson

Rome, , Italy

Site Status

IRCCS Santa Lucia Foundation

Rome, , Italy

Site Status

University of Amsterdam

Amsterdam, , Netherlands

Site Status

Krakowska Akademia Neurologii Sp. z o. o

Krakow, , Poland

Site Status

NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki

Lodz, , Poland

Site Status

Neuro-Care SP z o. o.

Siemianowice Śląskie, , Poland

Site Status

Oddział Neurologii ul. L. Kondratowicza 8

Warsaw, , Poland

Site Status

Hospital Braga

Braga, , Portugal

Site Status

CNS - Campus Neurologico Senior

Torres Vedras, , Portugal

Site Status

Kazan State Medical University

Kazan', , Russia

Site Status

Federal Siberian Scientic Clinical Center of FMBA

Krasnoyarsk, , Russia

Site Status

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

Novosibirsk, , Russia

Site Status

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

Saint Petersburg, , Russia

Site Status

Siberian State Medical University

Tomsk, , Russia

Site Status

Nemocnica akad. L. Derera

Bratislava, , Slovakia

Site Status

Univerzitna nemocnica L. Pasteura Kosice

Košice, , Slovakia

Site Status

Hospital Universitario central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status

Hospital General Universitario de Elche, Edificio principal

Alicante, , Spain

Site Status

Hospital Universitari de la Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari General de Catalunya

Barcelona, , Spain

Site Status

Hospital Universitario de Burgos

Burgos, , Spain

Site Status

Complejo Hospitalario Ruber Juan Bravo

Madrid, , Spain

Site Status

Hospital Universitario La Princesa

Madrid, , Spain

Site Status

Hospital Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Infanta Sofia

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocío, Laboratorio 104.

Seville, , Spain

Site Status

Hospital Universitario y Politcnico de La Fe

Valencia, , Spain

Site Status

Clinic "Dopomoga Plus"

Kyiv, , Ukraine

Site Status

Institute of Gerontolgoy - Parkinsons disease Treatment Centre

Kyiv, , Ukraine

Site Status

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

Poltava, , Ukraine

Site Status

Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital

Vinnytsia, , Ukraine

Site Status

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

Zaporizhzhya, , Ukraine

Site Status

King's College hospital

London, , United Kingdom

Site Status

St Georges University Hospital

London, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

Clinical Ageing research Unit

Newcastle, , United Kingdom

Site Status

University Hospitals Plymouth NHS Trust

Plymouth, , United Kingdom

Site Status

Countries

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United States Austria Belgium Czechia France Hungary Israel Italy Netherlands Poland Portugal Russia Slovakia Spain Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38499015 (View on PubMed)

Related Links

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Other Identifiers

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ND0612-317

Identifier Type: -

Identifier Source: org_study_id

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