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

NCT ID: NCT02726386

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-04
• Study Completion Date: 2027-02-28

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).

Detailed Description

This is a multi-center, international, open-label, safety study of ND0612, a solution of LD/CD delivered via a pump system as a continuous SC infusion in subjects with advanced PD. Two cohorts of subjects are candidates for this study: subjects who completed treatment in study ND0612H-006 within one month prior to enrollment (Cohort 1) and ND0612 naïve subjects or subjects who completed treatment in a ND0612 clinical study more than one month before screening (Cohort 2). After screening procedures and confirmation of the inclusion/exclusion criteria, subjects and their study partners will be trained and assisted at their homes during the first week of treatment on the proper operation of the pump system. One mandatory home visit will be performed during the first week and then on a monthly basis during 12-months of treatment. Subjects will return for in-clinic visits at Week 1 and at Months 1, 2, 3, 4, 6, 9, and 12 for assessment of safety and efficacy variables. Subjects will be allowed to continue with study treatment for an optional treatment extension period of up to Month 102 and the clinic visits will be performed every 3 months to assess subject long-term safety. Safety follow-up visits will occur 1, 2, and 3 months after the last SC infusion of ND0612 or after early termination.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

24-hour dosing regimen

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.

Group Type: EXPERIMENTAL

ND0612

Intervention Type: DRUG

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

16-hour dosing regimen

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.

Group Type: EXPERIMENTAL

ND0612

Intervention Type: DRUG

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

Interventions

ND0612

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

Intervention Type: DRUG

Other Intervention Names

ND0612H

Eligibility Criteria

Inclusion Criteria

Cohort 1.

1. Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).

2. Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012.

3. 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.

1. Male and female PD subjects of any race aged at least 30 years who sign an IRB/EC-approved ICF.

2. PD diagnosis consistent with the UK Brain Bank Criteria.

3. Modified Hoehn & Yahr scale in "ON" state of stage ≤3.

4. 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.

5. Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.

6. 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.

7. Must have a minimum of 2 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.

8. 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.

9. Mini Mental State Examination (MMSE) score ≥26.

10. No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.

11. 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 participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug. 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.

12. Willing and able to administer the SC infusion alone or with the assistance of a study partner after a screening period of up to 40 days and willing and able to comply with study requirements.

13. Subjects should have a named study partner.

Exclusion Criteria

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.

1. Atypical or secondary parkinsonism.

2. Acute psychosis or hallucinations in past 6 months.

3. 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.

4. 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).

5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit.

6. Prior neurosurgical procedure for PD, or Duodopa treatment

7. Subjects with a history of drug abuse or alcoholism within the past 12 months.

8. Clinically significant ECG rhythm abnormalities.

9. 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.

10. Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NeuroDerm Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurence Salin, MD

Role: STUDY_DIRECTOR

NeuroDerm Ltd.

Locations

Clintrial s.r.o.

Prague, , Czechia

Vestra Clinics, s.r.o.

Rychnov nad Kněžnou, , Czechia

Centre Hospitalier d'Aix

Aix-en-Provence, , France

CHU d'Amiens, Hopital Sud

Amiens, , France

Hopital Neurologique Pierre Wertheimer

Bron, , France

Hôpital Gabriel Montpied

Clermont-Ferrand, , France

Hopital Roger Salengro

Lille, , France

Hopital de la Timone

Marseille, , France

CHU de Poitiers

Poitiers, , France

Kliniken Beelitz GmbH

Beelitz-Heilstätten, , Germany

St. Josefs Hospital

Bochum, , Germany

Klinikum-Bremerhaven Reinkenheide

Bremerhaven, , Germany

Xenoscience

Phoenix, Arizona, United States

Clinical Trials Inc.

Little Rock, Arkansas, United States

The Parkinsons and Movement Disorder Institute

Fountain Valley, California, United States

Neuro Pain Medical Center

Fresno, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

Parkinson's Disease and Movement Disorder Center of Boca Raton

Boca Raton, Florida, United States

MD Clinical

Hallandale, Florida, United States

Infinity Clinical Research, LLC

Hollywood, Florida, United States

University of Florida Health at Jacksonville

Jacksonville, Florida, United States

Neurology Associates, PA

Maitland, Florida, United States

Parkinsons Disease Treatment Center of Southwest Florida

Port Charlotte, Florida, United States

Suncoast Neuroscience Associates

St. Petersburg, Florida, United States

Infinity Clinical Research, LLC

Sunrise, Florida, United States

USF Health Parkinson's Disease and Movement Disorders

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

Unity Point Health

Des Moines, Iowa, United States

University of Maryland, Neurology

Baltimore, Maryland, United States

QUEST Research Institute

Farmington Hills, Michigan, United States

Henry Ford Hospital

West Bloomfield, Michigan, United States

Pyramid Clinical Research

Somerset, New Jersey, United States

University of Cincinnati

Cincinnati, Ohio, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

Synergy Trials

Richmond, Virginia, United States

Sentara Neuroscience Institute

Virginia Beach, Virginia, United States

Premier Research

Spokane, Washington, United States

Medical University Innsbruck

Innsbruck, , Austria

NEUROHK, s.r.o.

Choceň, , Czechia

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, , Germany

Klinik Haag

Haag in Oberbayern, , Germany

Universitaets-und Rehabilitationskliniken Ulm

Ulm, , Germany

Barzilai MC

Ashkelon, , Israel

Hadassah Medical Center, Ein-Kerem Campus

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

University Foundation

Chieti, , Italy

AOU Pisa

Pisa, , Italy

IRCCS San Raffaele Pisana

Rome, , Italy

IRCCS Hospital San Camillo Venice

Venice, , Italy

Centrum Medyczne PLEJADY

Krakow, , Poland

Krakowska Akademia Neurologii Sp. z o.o.

Krakow, , Poland

Indywidualna Praktyka Lekarska prof. dr hab

Lublin, , Poland

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Countries

United States; Austria; Czechia; France; Germany; Israel; Italy; Poland; Spain

References

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.

Reference Type: RESULT

PMID: 34496081 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ND0612H-012

Identifier Type: -

Identifier Source: org_study_id