A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease

NCT02577523 | Completed Phase 2 Results DMC

• 1 other identifier: ND0612H-006
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 11

Brief Summary

This is a multicenter, parallel-group, rater-blinded, randomized clinical study in subjects with advanced PD investigating the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H, a solution of LD/CD delivered via a pump system as a continuous SC infusion, compared to standard oral LD/CD. After screening, subjects will undergo 1 day of standard oral LD/CD inpatient dosing followed by 2 days of inpatient treatment with 1 of 2 randomly allocated (1:1 randomization ratio) dosing regimens of ND0612H continuous SC infusion. Subjects will then continue on a maintenance dose of the assigned ND0612H dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug for a total of about 2.5 months of participation for each subject enrolled into the trial.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Change in Daily "OFF" Time

  Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. The changes in "OFF" time as hours (normalized to 16 hrs of awake time) during the 8 hrs of data collection were estimated. Negative change from baseline for "OFF" time indicates improvement.

  Baseline to Day 28

Secondary Outcomes (7)

• The Percentage of Subjects With Full "ON" at Approximately 08:00 and Approximately 09:00, as Determined by the Subject

  Baseline to Day 28

• Change in Daily "Good ON" Time as Assessed by a Blinded Rater

  Baseline to Day 28

• Change in Morning UPDRS Part III (Motor) Scores

  Baseline to Day 28

• Change in UPDRS Part II (ADL) Scores

  Baseline to Day 28

• CGI-Improvement (CGI-I) Score as Assessed by Investigator

  Baseline to Day 28

Study Arms (2)

ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1

EXPERIMENTAL

Dosing Regimen 1 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 24 hours.

Drug: ND0612 (Levodopa/Carbidopa solution)

ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2

EXPERIMENTAL

Dosing Regimen 2 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 14 hours. Infusion started at wake-up time supplemented with an oral IR LD/CD tablet.

Drug: ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD

Interventions

ND0612 (Levodopa/Carbidopa solution) DRUG

The total daily dose of levodopa/carbidopa 720/90 mg. Device: CRONO TWIN pump system.

Also known as: Regimen 1 - 24-hr infusion

ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1

ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD DRUG

The total daily dose levodopa/carbidopa from ND0612 538/67 mg. Morning dose of oral IR-LD/CD 150/15 mg. Device: CRONO TWIN pump system.

Also known as: Regimen 2 - 14-hr infusion

ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (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 (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least 2 other classes of anti-PD medications in a therapeutic dose for at least 30 consecutive days each.
• 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 administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612H treatment period.
• Must have a minimum of 2.5 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.
• Female subjects must be surgically sterile, 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, a barrier method of birth control \[e.g., condoms with contraceptive foams, diaphragms with contraceptive jelly\], 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.
• Willingness and ability to comply with study requirements

You may not qualify if:

• 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 or the eligibility reviewer, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
• 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.
• Subjects who are not willing to operate the pump system.

Sponsors & Collaborators

• NeuroDerm Ltd.: lead

Study Sites (11)

Northwestern University

Chicago, Illinois, 60611, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Medical University Innsbruck

Innsbruck, A- 4060, Austria

Location

Rabin Medical Center

Petah Tikva, 4941492, 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

Fondazione Ospedale San Camillo - I.R.C.C.S.

Venice, 30126, Italy

Location

Related Publications (1)

• Olanow CW, Espay AJ, Stocchi F, Ellenbogen AL, Leinonen M, Adar L, Case RJ, Orenbach SF, Yardeni T, Oren S, Poewe W; 006 study group. Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study. J Parkinsons Dis. 2021;11(1):177-186. doi: 10.3233/JPD-202285.

  PMID: 33164945 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Results Point of Contact

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

laurence@neuroderm.com

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: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2015
• First Posted: October 16, 2015
• Study Start: December 29, 2015
• Primary Completion: December 20, 2016
• Study Completion: January 31, 2017
• Last Updated: May 25, 2023
• Results First Posted: March 16, 2022

Record last verified: 2023-05

Locations

IT (4); AU (1); US (3); IL (3)