Clinical trial • Phase III • Neurology

carbidopa, levodopa for Parkinson's disease

Phase III trial of carbidopa, levodopa for Parkinson's disease.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Parkinson's disease
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
26-03-2024
First CTIS Authorization Date
17-05-2024

Trial design

Randomised, open-label, test group (group a): active nd0612 infusion (continuous subcutaneous nd0612 infusion) + placebo ir-ld/cd (white) + active ir-ld/cd (grey). control group (group b): active ir-ld/cd (oral immediate-release levodopa/carbidopa; ir-ld/cd 100/25 mg tablets with regimen adjusted per investigator, inclusion requires at least 4 doses/day and ≥400 mg/day levodopa or equivalent) + placebo infusion + placebo ir-ld/cd (grey). Phase III trial across 31 sites in Austria, Czechia, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Test Group (Group A): Active ND0612 infusion (continuous subcutaneous ND0612 infusion) + placebo IR-LD/CD (white) + active IR-LD/CD (grey). Control Group (Group B): Active IR-LD/CD (oral immediate-release levodopa/carbidopa; IR-LD/CD 100/25 mg tablets with regimen adjusted per investigator, inclusion requires at least 4 doses/day and ≥400 mg/day levodopa or equivalent) + placebo infusion + placebo IR-LD/CD (grey).
Target Sample Size
225
Trial Duration For Participant
224

Eligibility

Recruits 225 Vulnerable population selected. Participants must sign an IRB/EC-approved informed consent form (ICF); a named study partner must also sign the ICF. The protocol requires MMSE ≥ 24 and uses study partners for participant support/diary completion, indicating procedures for participants who may need assistance..

Pregnancy Exclusion
All female subjects must be non-lactating and not pregnant and have a negative urine pregnancy test at Screening and at Enrollment (IR D1/ V2).
Vulnerable Population
Vulnerable population selected. Participants must sign an IRB/EC-approved informed consent form (ICF); a named study partner must also sign the ICF. The protocol requires MMSE ≥ 24 and uses study partners for participant support/diary completion, indicating procedures for participants who may need assistance.

Inclusion criteria

  • {"criterion_text":"- Male and female subjects with PD of any race at least 30 years of age who sign an Institutional Review Board/Ethics Committee–approved informed consent form (ICF).\n- Subjects and/or study partners must demonstrate ability to keep accurate diary entries of PD symptoms (\"ON/OFF\" diaries) with at least 75% concordance with the Blinded Efficacy Rater by the end of the diary training session during the Screening Period, including at least 1 \"OFF\" assessment..\n- Mini Mental State Examination (MMSE) score ≥ 24.\n- Approval for entry into the study by an independent EAC.\n- Female subjects must be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation); postmenopausal (defined as cessation of menses for at least 1 year); or willing to practice a highly effective method of contraception. All female subjects must be non-lactating and not pregnant and have a negative urine pregnancy test at Screening and at Enrollment (IR D1/ V2). Female subjects of childbearing potential must practice a highly effective method of contraception (such methods include combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation: oral / intravaginal; transdermal / progestogen-only hormonal contraception associated with inhibition of ovulation: oral / injectable; implantable / intrauterine device [IUD] / intrauterine hormone-releasing system [IUS]/ bilateral tubal occlusion / vasectomized partner/ sexual abstinence) from 1 month before Enrollment (IR D1/V2) until 1 month after the last dose of study treatment. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, the subject and sexual partner must comply with the contraceptive requirements detailed above.\n- Subjects must have a named study partner that signed the ICF.\n- Willingness and ability to comply with study requirements.\n- Parkinson's disease diagnosis consistent with the UK Brain Bank Criteria.\n- Modified Hoehn and Yahr scale in \"ON\" stage ≤ 3.\n- Subjects must experience motor fluctuations and experience an average of at least 2.5 hours daily (with a minimum of 2 hours every day) in the \"OFF\" state during the waking hours as confirmed by an adequately completed \"ON/OFF\" diary over 3 days.\n- Subject treatment should be at least 4 doses/day of LD/DDI (or at least 3 doses/day of extended release LD/DDI, e.g., Rytary) and at least 400 mg/day of LD, or equivalent according to the conversion table, and, according to the Investigator's judgement, the subject experiences motor fluctuations that cannot be further improved by adjusting anti-PD medications.\n- Subjects and/or study partners have no impediment that may prevent them from operating the pump system."}

Exclusion criteria

  • {"criterion_text":"- Atypical or secondary Parkinsonism.\n- Use of non-selective monoamine oxidase inhibitors (e.g., phenelzine, isocarboxazid, tranylcypromine) within 4 weeks before enrollment.\n- Subjects with severe disabling dyskinesias, based on Investigator's discretion.\n- Current or previous diagnosis of Dopamine Dysregulation Syndrome.\n- Subjects who answered \"yes\" to questions 4 or 5 of the C-SSRS within the last 5 years.\n- Use of subcutaneous (SC) apomorphine injections, sublingual apomorphine, or inhaled LD within 4 weeks before the enrollment.\n- Concomitant therapy or within 28 days before enrollment with: metoclopramide, reserpine, methylphenidate, or amphetamines, well as neuroleptics; exception in case of Quetiapine and Pimavanserin use: (1) allowed only in case it had been used for a period of at least 3 months before enrollment, (2) subject is on stable therapy for at least 3 months (3) underlying psychosis to be under control and anticipating no changes to the dosage of the medication throughout the study.\n- Subjects who have previously undergone treatment for PD with a surgical intervention (e.g., pallidotomy, thalamotomy, transplantation, deep brain stimulation procedures, gene therapy), Duodopa®/Duopa®, or continuous dopaminergic or apomorphine infusion. Subjects who have discontinued Duodopa®/Duopa® treatment at least 6 months before enrollment and have undergone stoma closure surgery at least 6 months before enrollment, may be included in this study. Subjects who are planning to undergo treatment for PD with a surgical intervention will be enrolled at the Investigator's discretion.\n- Subjects with a history of alcohol or substance abuse within the past 12 months.\n- Subjects who do not have sufficient SC tissue for SC infusion treatment.\n- Subjects who have previously participated in studies ND0612H-006 and/or ND0612H-012.\n- Use of monoamine-depleting agents (e.g., reserpine, tetrabenazine, deutetrabenazine, valbenazine, xenazine) within 4 weeks before enrollment.\n- Subjects who have taken experimental medications within 30 days before enrollment.\n- Known allergy to the study drug or placebo or any of their excipients.\n- Impulse control disorder within the past 2 years, if considered clinically significant by the investigator.\n- Acute psychosis or troublesome hallucinations in the past 6 months.\n- Subjects with clinically significant or unstable medical, surgical, or psychiatric condition or laboratory abnormalities which, in the opinion of the Investigator or the EAC, represents a safety risk, makes the subject unsuitable for study entry, or potentially unable to complete all aspects of the study.\n- History of significant skin conditions or disorders (e.g., psoriasis, atopic dermatitis, etc.) or evidence of different lesions (e.g., sunburn, acne, scar tissue, tattoo, open wound, branding, or pigmentation) that, in the Investigator's opinion, would interfere with the infusion of the study drug or could interfere with study assessments.\n- Clinically significant ECG abnormalities.\n- Renal or liver dysfunction that may alter drug metabolism including Screening Visit serum levels of creatinine > 1.5 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 × upper limit of normal, and total bilirubin > 2.5 mg/dL.\n- Any malignancy in the 5 years before enrollment, except basal cell carcinoma of the skin, squamous cell carcinoma in situ, or cervical carcinoma in situ that have been successfully treated.\n- Subjects with narrow angle glaucoma."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is the change from Baseline to the end of the DBDD Maintenance Period in the mean daily \"ON\" time without troublesome dyskinesia adjusted to subject's waking hours and normalized to 16 waking hours, based on subject's \"ON/OFF\" diary assessments on the 3 consecutive days before the visit.","definition_or_measurement_approach":"Change from Baseline to end of DBDD Maintenance Period in mean daily \"ON\" time without troublesome dyskinesia, adjusted to subject's waking hours and normalized to 16 waking hours, measured using subject-completed \"ON/OFF\" diary assessments over the 3 consecutive days before the visit."}

Secondary endpoints

  • {"endpoint_text":"- The key secondary efficacy endpoint is the change from Baseline to the end of the DBDD Maintenance Period (DB W12) in the mean daily \"OFF\" time adjusted to subject's waking hours and normalized to 16 waking hours, based on subject's \"ON/OFF\" diary assessments on the 3 consecutive days before the visits.","definition_or_measurement_approach":"Change from Baseline to end of DBDD Maintenance Period (DB W12) in mean daily \"OFF\" time adjusted to subject's waking hours and normalized to 16 waking hours, measured using subject-completed \"ON/OFF\" diary assessments over the 3 consecutive days before the visits."}

Recruitment

Planned Sample Size
225
Recruitment Window Months
86
Consent Approach
Participants provide written informed consent using an IRB/EC-approved informed consent form (ICF). A named study partner must also sign the ICF. Multiple language versions of the ICF/SIS are provided (examples in the documents include English, French, Spanish, Portuguese, Italian, Polish, Slovak, Dutch), and consent processes follow local IRB/EC approval.

Geography

Total Number Of Sites
31
Total Number Of Participants
156

Austria

Latest Decision Or Authorization Date
22-05-2024
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Medizinische Universitaet Innsbruck
Department Name
University Hospital for Neurology
Principal Investigator Name
Werner Poewe
Principal Investigator Email
werner.poewe@i-med.ac.at
Contact Person Name
Werner Poewe
Contact Person Email
werner.poewe@i-med.ac.at

Czechia

Latest Decision Or Authorization Date
21-05-2024
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Axon Clinical s.r.o.
Principal Investigator Name
Kateřina Zárubová
Principal Investigator Email
katzar@centrum.cz
Contact Person Name
Kateřina Zárubová
Contact Person Email
katzar@centrum.cz

Italy

Latest Decision Or Authorization Date
18-06-2024
Number Of Sites
7
Number Of Participants
41

Sites

Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
Dipartimento di Scienze Mediche e Chirurgiche Avanzate (DAMSS) - Università degli studi della Campan
Principal Investigator Name
Alessandro Tessitore
Principal Investigator Email
alessandro.tessitore@unicampania.it
Contact Person Name
Alessandro Tessitore
Site Name
Universita' Degli Studi G. D'annunzio Di Chieti
Department Name
Department of Neuroscience, Imaging and Medical Sciences
Principal Investigator Name
Astrid Thomas
Principal Investigator Email
athomas@unich.it
Contact Person Name
Astrid Thomas
Contact Person Email
athomas@unich.it
Site Name
Fondazione Santa Lucia IRCCS
Department Name
Laboratory of Neuropsychiatry - Department of Clinical and Behavioral Neurology
Principal Investigator Name
Clelia Pellicano
Principal Investigator Email
c.pellicano@hsantalucia.it
Contact Person Name
Clelia Pellicano
Contact Person Email
c.pellicano@hsantalucia.it
Site Name
Irccs San Raffaele Roma S.r.l. (Cassino)
Department Name
San Raffaele Cassino - Parkinson Disease Center
Principal Investigator Name
Maria Francesca De Pandis
Principal Investigator Email
maria.depandis@sanraffaele.it
Contact Person Name
Maria Francesca De Pandis
Contact Person Email
maria.depandis@sanraffaele.it
Site Name
Irccs San Raffaele Roma S.r.l. (Rome)
Department Name
Department of Neurology – Clinical Trial Center
Principal Investigator Name
Fabrizio Stocchi
Principal Investigator Email
fabrizio.stocchi@sanraffaele.it
Contact Person Name
Fabrizio Stocchi
Site Name
Azienda USL Toscana Sud Est
Department Name
Ospedale della Misericordia, UOC Neurologia
Principal Investigator Name
Roberto Marconi
Principal Investigator Email
roberto.marconi@uslsudest.toscana.it
Contact Person Name
Roberto Marconi
Site Name
Humanitas Mirasole S.p.A.
Department Name
U.O Neurologia I
Principal Investigator Name
Alberto Albanese
Principal Investigator Email
alberto.albanese@humanitas.it
Contact Person Name
Alberto Albanese
Contact Person Email
alberto.albanese@humanitas.it

Poland

Latest Decision Or Authorization Date
17-05-2024
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki
Department Name
Not applicable
Principal Investigator Name
Andrzej Bogucki
Principal Investigator Email
andrzej.bogucki@umed.lodz.pl
Contact Person Name
Andrzej Bogucki
Contact Person Email
andrzej.bogucki@umed.lodz.pl
Site Name
Krakowska Akademia Neurologii Sp. z o.o.
Department Name
Not applicable
Principal Investigator Name
Monika Rudzińska-Bar
Principal Investigator Email
mrudzinska@sum.edu.pl
Contact Person Name
Monika Rudzińska-Bar
Contact Person Email
mrudzinska@sum.edu.pl
Site Name
Neuro-Care Sp. z o.o. sp.k.
Department Name
Not applicable
Principal Investigator Name
Gabriela Kłodowska
Principal Investigator Email
g.klodowska@neuro-care.pl
Contact Person Name
Gabriela Kłodowska
Contact Person Email
g.klodowska@neuro-care.pl

Slovakia

Latest Decision Or Authorization Date
20-05-2024
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
University Hospital Bratislava
Department Name
II. Neurologicka klinika LF UK a UNB
Principal Investigator Name
Peter Valkovic
Principal Investigator Email
peter.valkovic@gmail.com
Contact Person Name
Peter Valkovic
Contact Person Email
peter.valkovic@gmail.com

France

Latest Decision Or Authorization Date
11-06-2024
Number Of Sites
7
Number Of Participants
11

Sites

Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Centre d’Investigation Clinique Service de Neurologie B8
Principal Investigator Name
Olivier RASCOL
Principal Investigator Email
olivier.rascol@univ-tlse3.fr
Contact Person Name
Olivier RASCOL
Contact Person Email
olivier.rascol@univ-tlse3.fr
Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
Service de Neurologie
Principal Investigator Name
Giovanni Castelnovo
Principal Investigator Email
giovanni.castelnovo@chu-nimes.fr
Contact Person Name
Giovanni Castelnovo
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Service de Neurologie
Principal Investigator Name
Ana Raquel MARQUES
Principal Investigator Email
ar_marques@chu-clermontferrand.fr
Contact Person Name
Ana Raquel MARQUES
Site Name
Centre Hospitalier Regional De Marseille
Department Name
264 rue Saint Pierre
Principal Investigator Name
Jean-Philippe AZULAY
Principal Investigator Email
jean-philippe.azulay@ap-hm.fr
Contact Person Name
Jean-Philippe AZULAY
Contact Person Email
jean-philippe.azulay@ap-hm.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Service de neurologie
Principal Investigator Name
Caroline GIORDANA
Principal Investigator Email
giordana.c@chu-nice.fr
Contact Person Name
Caroline GIORDANA
Contact Person Email
giordana.c@chu-nice.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Unite d’Investigation Clinique (UIC) - neurologie
Principal Investigator Name
Anne-Gaelle CORBILLE
Principal Investigator Email
annagaelle.corbille@chu-nantes.fr
Contact Person Name
Anne-Gaelle CORBILLE
Site Name
Hospices Civils De Lyon
Department Name
Hopital de jour recherche (Unite 502 - Recherche)
Principal Investigator Name
Chloe LAURENCIN
Principal Investigator Email
chloe.laurencin@chu-lyon.fr
Contact Person Name
Chloe LAURENCIN
Contact Person Email
chloe.laurencin@chu-lyon.fr

Spain

Latest Decision Or Authorization Date
22-05-2024
Number Of Sites
8
Number Of Participants
55

Sites

Site Name
Hospital Universitari General De Catalunya
Department Name
Neurology
Principal Investigator Name
Ernest Balaguer Martínez
Principal Investigator Email
ebalaguer@quironsalud.es
Contact Person Name
Ernest Balaguer Martínez
Contact Person Email
ebalaguer@quironsalud.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Neurology
Principal Investigator Name
Jorge Hernandez Varas
Principal Investigator Email
hernandezvarajorge76@gmail.com
Contact Person Name
Jorge Hernandez Varas
Contact Person Email
hernandezvarajorge76@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Neurology
Principal Investigator Name
Francisco Grandas
Principal Investigator Email
francisco.grandas@salud.madrid.org
Contact Person Name
Francisco Grandas
Site Name
Hospital Universitario De La Princesa
Department Name
Neurology
Principal Investigator Name
Lydia López Manzanares
Principal Investigator Email
lydialopez@hotmail.com
Contact Person Name
Lydia López Manzanares
Contact Person Email
lydialopez@hotmail.com
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Neurology
Principal Investigator Name
Jaime Kulisevski
Principal Investigator Email
jkulisevsky@santpau.cat
Contact Person Name
Jaime Kulisevski
Contact Person Email
jkulisevsky@santpau.cat
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Neurology
Principal Investigator Name
Pablo Mir Rivera
Principal Investigator Email
pmir@us.es
Contact Person Name
Pablo Mir Rivera
Contact Person Email
pmir@us.es
Site Name
Hospital General Universitario De Elche
Department Name
Neurology
Principal Investigator Name
Eric Freire Alvarez
Principal Investigator Email
dr.freyre@gmail.com
Contact Person Name
Eric Freire Alvarez
Contact Person Email
dr.freyre@gmail.com
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Neurology
Principal Investigator Name
Juan Carlos Martínez Castrillo
Principal Investigator Email
jmcastrillo@gmail.com
Contact Person Name
Juan Carlos Martínez Castrillo
Contact Person Email
jmcastrillo@gmail.com

Belgium

Latest Decision Or Authorization Date
21-05-2024
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Centre hospitalier universitaire de Tivoli Institut medical des Mutualites socialistes
Department Name
Neurology
Principal Investigator Name
Marta Lamartine
Principal Investigator Email
mlamarti@chu-tivoli.be
Contact Person Name
Marta Lamartine
Contact Person Email
mlamarti@chu-tivoli.be

Portugal

Latest Decision Or Authorization Date
17-05-2024
Number Of Sites
2
Number Of Participants
18

Sites

Site Name
CCAB Centro Clinico Academico Braga Associacao (Hospital Braga)
Department Name
Hospital Braga
Principal Investigator Name
Sara Varanda
Principal Investigator Email
sara.varanda@ulsb.min-saude.pt
Contact Person Name
Sara Varanda
Contact Person Email
sara.varanda@ulsb.min-saude.pt
Site Name
CNS Saude Lda.
Department Name
Neurology
Principal Investigator Name
Joaquim Ferreira
Principal Investigator Email
joaquimjferreira@gmail.com
Contact Person Name
Joaquim Ferreira
Contact Person Email
joaquimjferreira@gmail.com

Sponsor

Primary sponsor

Full Name
Neuroderm Ltd.
Organisation Type
Pharmaceutical company
Country Of Registered Address
Israel

Contract research organisations

Name
IQVIA Limited
Responsibilities
clinical trial educator
Name
Syneos Health Netherlands B.V.
Responsibilities
multiple operational roles (sponsorDuties codes: 1,11,12,2,6,7,8)
Name
WCG Clinical Inc.
Responsibilities
sponsorDuties code: 8
Name
Medidata Solutions Inc.
Responsibilities
sponsorDuties code: 7

Third parties

  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"patient transport","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"France","full_name":"Novasco","duties_or_roles":"patient transport","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Medical product shipment","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"sponsorDuties code: 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Emsere B.V.","duties_or_roles":"equipment rental","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"clinical trial educator","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 1,11,12,2,6,7,8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
ND0612
Active Substance
carbidopa, levodopa
Modality
Small molecule
Routes Of Administration
Subcutaneous (continuous subcutaneous infusion)
Route
Subcutaneous
Authorisation Status
Authorised (prodAuthStatus: 1 indicated in product record)
Frequency
Continuous subcutaneous infusion (as per protocol title and device information)
Maximum Dose
720 mg/day
Investigational Product Name
IR-LD/CD
Active Substance
carbidopa, levodopa
Modality
Small molecule
Routes Of Administration
Oral (tablets)
Route
Oral
Authorisation Status
Authorised (prodAuthStatus: 1 indicated in product record)
Frequency
Multiple daily oral doses; inclusion requires at least 4 doses/day of LD/DDI (or ≥3 doses/day for extended release) and at least 400 mg/day levodopa or equivalent
Maximum Dose
At least 400 mg/day levodopa (per inclusion criteria)
Investigational Product Name
PLACEBO for LD/CD Capsules (white)
Modality
Other
Routes Of Administration
Oral (capsule)
Route
Oral
Authorisation Status
Not applicable / placebo
Investigational Product Name
PLACEBO for LD/CD Capsules (grey)
Modality
Other
Routes Of Administration
Oral (capsule)
Route
Oral
Authorisation Status
Not applicable / placebo
Investigational Product Name
PLACEBO TO ND0612 (solution for infusion, subcutaneous)
Modality
Other
Routes Of Administration
Subcutaneous (solution for infusion)
Route
Subcutaneous
Authorisation Status
Not applicable / placebo
Combination Treatment
Yes

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