A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease

NCT02726386 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: ND0612H-012
• Study Type: interventional
• Target: 214
• Locations: 9 countries
• Sites: 57

Brief Summary

This is a multi-center, international, open-label, safety study of ND0612, a solution of levodopa/carbidopa (LD/CD) delivered via a pump system as a continuous SC infusion in subjects with advanced Parkinson's Disease (PD).

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Adverse Events (Long-term Safety)

  Long-term safety (systemic and local) assessment will be based on adverse events (AEs), with a focus on adverse events of special interest (AESI), i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.

  Baseline to Month 12

• Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability)

  Tolerability will be assessed based on the percentage of subjects that complete the 12-month treatment period of the study and the percentage of subjects who discontinue from the 12-month treatment period due to an AE.

  Baseline to Month 12

Secondary Outcomes (1)

• Adverse Events (Long-term Safety)

  Month 12 to Month 102

Other Outcomes (15)

• Change of Daily "ON" Time Without Troublesome Dyskinesia

  Baseline to Month 12

• Change of Daily "OFF" Time

  Baseline to Month 12

• Change of Total Daily Dose of Oral LD/DDI

  Baseline to Month 12

Study Arms (2)

24-hour dosing regimen

EXPERIMENTAL

Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen.

Drug: ND0612

16-hour dosing regimen

EXPERIMENTAL

Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening.

Drug: ND0612

Interventions

ND0612 DRUG

ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system

Also known as: ND0612H

16-hour dosing regimen; 24-hour dosing regimen

Eligibility Criteria

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

You may qualify if:

• Cohort 1.
• Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
• Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012.
• Willing and able to administer the SC infusion alone or with the assistance of a study partner and able to comply with the study specific procedures.
• Cohort 2.
• Male and female PD subjects of any race aged at least 30 years who sign an IRB/EC-approved ICF.
• PD diagnosis consistent with the UK Brain Bank Criteria.
• Modified Hoehn \& Yahr scale in "ON" state of stage ≤3.
• Taking at least 4 doses/day of LD/DDI (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least one other PD treatment for at least 30 days.
• Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
• Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped continuous apomorphine administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612 treatment period.
• Must have a minimum of 2 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.
• Must have predictable and well defined early morning "OFF" periods with a good response to LD for treatment of the early morning "OFF" in the judgement of the investigator.
• Mini Mental State Examination (MMSE) score ≥26.
• No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.

You may not qualify if:

• Cohort 1 and 2. Previously unable to tolerate ND0612 and/or have experienced intolerable adverse drug reactions associated with its use, regardless of the dosing regimen administered.
• Cohort 2.
• Atypical or secondary parkinsonism.
• Acute psychosis or hallucinations in past 6 months.
• Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
• Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated).
• Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit.
• Prior neurosurgical procedure for PD, or Duodopa treatment
• Subjects with a history of drug abuse or alcoholism within the past 12 months.
• Clinically significant ECG rhythm abnormalities.
• Renal or liver dysfunction that may alter drug metabolism including: serum creatinine \>1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 x upper limit of normal (ULN), total serum bilirubin \>2.5 mg/dL.
• Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.

Sponsors & Collaborators

• NeuroDerm Ltd.: lead

Study Sites (57)

Xenoscience

Phoenix, Arizona, 85004, United States

Location

Clinical Trials Inc.

Little Rock, Arkansas, 72205-6421, United States

Location

The Parkinsons and Movement Disorder Institute

Fountain Valley, California, 92708-5153, United States

Location

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113-2776, United States

Location

Parkinson's Disease and Movement Disorder Center of Boca Raton

Boca Raton, Florida, 33486-2359, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Infinity Clinical Research, LLC

Hollywood, Florida, 33021, United States

Location

University of Florida Health at Jacksonville

Jacksonville, Florida, 32209, United States

Location

Neurology Associates, PA

Maitland, Florida, 32751-4723, United States

Location

Parkinsons Disease Treatment Center of Southwest Florida

Port Charlotte, Florida, 33980, United States

Location

Suncoast Neuroscience Associates

St. Petersburg, Florida, 33713-8844, United States

Location

Infinity Clinical Research, LLC

Sunrise, Florida, 33351, United States

Location

USF Health Parkinson's Disease and Movement Disorders

Tampa, Florida, 33613, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Unity Point Health

Des Moines, Iowa, 50309, United States

Location

University of Maryland, Neurology

Baltimore, Maryland, 21201, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Henry Ford Hospital

West Bloomfield, Michigan, 48322-3013, United States

Location

Pyramid Clinical Research

Somerset, New Jersey, 08873-3448, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

Synergy Trials

Richmond, Virginia, 23226, United States

Location

Sentara Neuroscience Institute

Virginia Beach, Virginia, 23456-0168, United States

Location

Premier Research

Spokane, Washington, 99202-1461, United States

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

NEUROHK, s.r.o.

Choceň, 565 01, Czechia

Location

Clintrial s.r.o.

Prague, 100 00, Czechia

Location

Vestra Clinics, s.r.o.

Rychnov nad Kněžnou, 516 01, Czechia

Location

Centre Hospitalier d'Aix

Aix-en-Provence, 13616, France

Location

CHU d'Amiens, Hopital Sud

Amiens, 80054, France

Location

Hopital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

Hôpital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hopital Roger Salengro

Lille, 59037, France

Location

Hopital de la Timone

Marseille, 13385, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

Kliniken Beelitz GmbH

Beelitz-Heilstätten, 14547, Germany

Location

St. Josefs Hospital

Bochum, 44791, Germany

Location

Klinikum-Bremerhaven Reinkenheide

Bremerhaven, 27574, Germany

Location

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, 1307, Germany

Location

Klinik Haag

Haag in Oberbayern, 83527, Germany

Location

Universitaets-und Rehabilitationskliniken Ulm

Ulm, 89081, Germany

Location

Barzilai MC

Ashkelon, 7830604, Israel

Location

Hadassah Medical Center, Ein-Kerem Campus

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 56520, Israel

Location

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

University Foundation

Chieti, 66100, Italy

Location

AOU Pisa

Pisa, 56126, Italy

Location

IRCCS San Raffaele Pisana

Rome, 00163, Italy

Location

IRCCS Hospital San Camillo Venice

Venice, 30126, Italy

Location

Centrum Medyczne PLEJADY

Krakow, 30-363, Poland

Location

Krakowska Akademia Neurologii Sp. z o.o.

Krakow, 31-505, Poland

Location

Indywidualna Praktyka Lekarska prof. dr hab

Lublin, 20-016, Poland

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Related Publications (1)

• Poewe W, Stocchi F, Arkadir D, Ebersbach G, Ellenbogen AL, Giladi N, Isaacson SH, Kieburtz K, LeWitt P, Olanow CW, Simuni T, Thomas A, Zlotogorski A, Adar L, Case R, Oren S, Fuchs Orenbach S, Rosenfeld O, Sasson N, Yardeni T, Espay AJ; BeyoND study group. Subcutaneous Levodopa Infusion for Parkinson's Disease: 1-Year Data from the Open-Label BeyoND Study. Mov Disord. 2021 Nov;36(11):2687-2692. doi: 10.1002/mds.28758. Epub 2021 Sep 8.

  PMID: 34496081 RESULT

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

Results Point of Contact

• Title: Laurence Salin, MD, Senior Medical Director
• Organization: NeuroDerm Ltd.

laurence@neuroderm.com

+33687548073

Study Officials

• Laurence Salin, MD

  NeuroDerm Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 1, 2016
• Study Start: May 4, 2016
• Primary Completion: September 9, 2019
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 30, 2025
• Results First Posted: May 6, 2023

Record last verified: 2025-05

Locations

AU (1); CZ (3); IT (4); PL (3); IL (5); DE (6); FR (7); ES (2); US (26)