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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Oral IR-LD/CD Adjustment | Other | Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks. |
|
| ND0612 Conversion | Other | ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ND0612 Solution for SC infusion | Combination Product | Levodopa/Carbidopa (LD/CD) solution administered SC via infusion pump |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| The change in daily OFF time | OFF time per patient diary | Baseline to the end of DBDD Maintenance Period (12 weeks) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alberto J Espay, MD, MSc | University of Cincinnati OH, USA | Principal Investigator |
| Olivier Rascol, MD, PhD | Toulouse University Hospital, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xenoscience | Phoenix | Arizona | 85004 | United States | ||
| University of Arkansas for Medical Sciences |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38499015 | Derived | 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. |
| Label | URL |
|---|---|
| European Union Clinical Trials Register | View source |
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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)
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Blinded Site Rater, Blinded Clinical Research Associates (CRAs), active drugs and matching placebos are identical in their appearances.
|
| Placebo for SC infusion | Combination Product | Placebo solution administered SC via infusion pump |
|
| Oral IR-LD/CD | Drug | Encapsulated LD/CD 100mg/25mg |
|
|
| Placebo for Oral IR-LD/CD | Drug | Encapsulated Placebo for LD/CD 100mg/25mg |
|
|
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Cedar- Sinai Medical Center Department of Neurology | Los Angeles | California | 90048 -1804 | United States |
| SC3 Research - Reseda | Reseda | California | 91335 | United States |
| University of California San Francisco | San Francisco | California | 94115 | United States |
| Rocky Mountain Movement Disorders Center | Englewood | Colorado | 80113 | United States |
| Hartford Healthcare Chase Family Movement Disorders Center | Vernon | Connecticut | 06066 | United States |
| Visionary Investigators Network | Aventura | Florida | 33180 | United States |
| Parkinsons Disease and Movement Disorders Center of Boca Raton | Boca Raton | Florida | 33486-2359 | United States |
| University of Florida Norman Fixel Institute for Neurological Diseases | Gainesville | Florida | 32608 | United States |
| Neurology Associates PA | Maitland | Florida | 32751-4723 | United States |
| USF Parkinson's Disease and Movement Disorders Center | Tampa | Florida | 33613 | United States |
| Neurology One | Winter Park | Florida | 32792 | United States |
| Emory University - Brain Health Center | Atlanta | Georgia | 30329 | United States |
| NeuroStudies | Decatur | Georgia | 30033 | United States |
| Hawaii Pacific Neuroscience | Honolulu | Hawaii | 96817 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Unity Point Health | Des Moines | Iowa | 50309 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| University of Kentucky, Neurology and Movement Disorder | Lexington | Kentucky | 40536-0284 | United States |
| Oschner Medical Center | New Orleans | Louisiana | 70121 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Michigan State University | East Lansing | Michigan | 48824 | United States |
| QUEST Research Institute | Farmington Hills | Michigan | 48334-2980 | United States |
| Henry Ford West Bloomfield Hospital | West Bloomfield | Michigan | 48322 | United States |
| Rutgers-Robert Wood Johnson Medical School | New Brunswick | New Jersey | 08901 | United States |
| Weill Cornell Medicine | New York | New York | 10021 | United States |
| Mount Sinai Medical center Movement Disorders Center | New York | New York | 10029 | United States |
| Duke University | Durham | North Carolina | 27705 | United States |
| University of Cincinnati | Cincinnati | Ohio | 45219 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Corporal Michael J. Crescenz VA Medical Center | Philadelphia | Pennsylvania | 19101-4511 | United States |
| Abington Neurological Associates LTD. | Willow Grove | Pennsylvania | 19090-1749 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Neurology Consultants of Dallas | Dallas | Texas | 75243 | United States |
| University of Vermont Medical Center | Burlington | Vermont | 05401 | United States |
| University of Virginia | Charlottesville | Virginia | 22908-0816 | United States |
| University of Wisconsin Madison | Madison | Wisconsin | 53705-2281 | United States |
| Medical University Innsbruck | Innsbruck | 6020 | Austria |
| CHU de Tivoli | La Louvière | 7100 | Belgium |
| Neurologicka klinika Fakutni nemocnice sv. Anny v Brne | Brno | 65691 | Czechia |
| Axon Clinical s.r.o. | Prague | 150 00 | Czechia |
| Hopital Neurologique | Bron | 69677 | France |
| Hopital Gabriel Montpied | Clermont-Ferrand | 63000 | France |
| CHU Nantes-Hopital Laennec | Nantes | 44800 | France |
| CHU de Nice Hpital Pasteur | Nice | 6002 | France |
| Chu Caremeau | Nîmes | GARD 30000 | France |
| Hopital Purpan | Toulouse | 31059 | France |
| University of Pecs, Clinical Center | Pécs | 7623 | Hungary |
| Shaare Zedek Medical Center | Jerusalem | 9103102 | Israel |
| Hadassah Medical Center, Ein Kerem | Jerusalem | 9112001 | Israel |
| Galilee Medical center- Nahariya | Nahariya | 22100 | Israel |
| Rabin Medical Center, Beilinson Hospital | Petah Tikva | 49100 | Israel |
| Chaim Sheba Medical Center | Ramat Gan | 5265601 | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | 64239 | Israel |
| Casa di Cura Villa Margherita | Arcugnano | 36057 | Italy |
| Centro Ricerca Parkinson San Raffaele Cassino | Cassino | 03043 | Italy |
| University Chieti CeSI MET Clinical research center-CRC | Chieti | 66100 | Italy |
| Ospedale di Grosseto, Azienda USL Toscana Sud Est | Grosseto | 58100 | Italy |
| Istituto Clinico Humanitas - IRCCS | Milan | 20089 | Italy |
| AOU University of Campania "Luigi Vanvitelli" | Naples | 80138 | Italy |
| IRCCS Fondazione C. Mondino | Pavia | 27100 | Italy |
| IRCCS San Raffaele Pisana | Roma | RM 163 | Italy |
| Policlinico Tor Vergata - UOSD Parkinson | Rome | 00133 | Italy |
| IRCCS Santa Lucia Foundation | Rome | 179 | Italy |
| University of Amsterdam | Amsterdam | 1105 | Netherlands |
| Krakowska Akademia Neurologii Sp. z o. o | Krakow | 31-505 | Poland |
| NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki | Lodz | 90-640 | Poland |
| Neuro-Care SP z o. o. | Siemianowice Śląskie | 41-100 | Poland |
| Oddział Neurologii ul. L. Kondratowicza 8 | Warsaw | 03-242 | Poland |
| Hospital Braga | Braga | 4710-243 | Portugal |
| CNS - Campus Neurologico Senior | Torres Vedras | 256-280 | Portugal |
| Kazan State Medical University | Kazan' | 420012 | Russia |
| Federal Siberian Scientic Clinical Center of FMBA | Krasnoyarsk | 660037 | Russia |
| Novosibirsk regional specialized scientific-practical neurological center on the basis City Clinical Hospital 34 | Novosibirsk | 630054 | Russia |
| The first Saint-Petersburg State Medical University named after IP Pavlov | Saint Petersburg | 197022 | Russia |
| Siberian State Medical University | Tomsk | 634050 | Russia |
| Nemocnica akad. L. Derera | Bratislava | 833 05 | Slovakia |
| Univerzitna nemocnica L. Pasteura Kosice | Košice | 04166 | Slovakia |
| Hospital Universitario central de Asturias | Oviedo | Principality of Asturias | 33011 | Spain |
| Hospital General Universitario de Elche, Edificio principal | Alicante | 03203 | Spain |
| Hospital Universitari de la Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital de La Santa Creu I Sant Pau | Barcelona | 08041 | Spain |
| Hospital Universitari General de Catalunya | Barcelona | 08195 | Spain |
| Hospital Universitario de Burgos | Burgos | 09006 | Spain |
| Complejo Hospitalario Ruber Juan Bravo | Madrid | 28006 | Spain |
| Hospital Universitario La Princesa | Madrid | 28006 | Spain |
| Hospital Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Universitario Ramon y Cajal | Madrid | 28034 | Spain |
| Hospital Clinico San Carlos | Madrid | 28040 | Spain |
| Hospital Universitario Infanta Sofia | Madrid | 28702 | Spain |
| Hospital Universitario Virgen del Rocío, Laboratorio 104. | Seville | 41013 | Spain |
| Hospital Universitario y Politcnico de La Fe | Valencia | 46026 | Spain |
| Clinic "Dopomoga Plus" | Kyiv | 04111 | Ukraine |
| Institute of Gerontolgoy - Parkinsons disease Treatment Centre | Kyiv | 4114 | Ukraine |
| Ukrainian Medical Stomatological Academy based on Poltava Regional Clinical Hospital n.a. M.V.Skliphosovskyy | Poltava | 36011 | Ukraine |
| Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital | Vinnytsia | 21005 | Ukraine |
| Municipal Non-commercial Institution '' City hospital #9" of Zaporizhzhya City Council | Zaporizhzhya | 69065 | Ukraine |
| King's College hospital | London | SE5 9RT | United Kingdom |
| St Georges University Hospital | London | SW17 0QT | United Kingdom |
| Directorate of Medicine & Integrated Care, Imperial College Healthcare NHS Trust | London | W6 8RF | United Kingdom |
| Clinical Ageing research Unit | Newcastle | NE4 5PL | United Kingdom |
| University Hospitals Plymouth NHS Trust | Plymouth | PL6 5FP | United Kingdom |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
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