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• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2015-005078-39-AT
• Date of registration: 09/03/2016
• Prospective Registration: Yes
• Primary sponsor: NeuroDerm Ltd.
• Public title: -
• Scientific title: A multicenter, parallel-group, rater-blinded, randomized clinical study investigating the efficacy, safety, tolerability and pharmacokinetics of 2 dosing regimens of ND0612H, a solution of levodopa/carbidopa delivered via a pump system as a continuous subcutaneous infusion in subjects with advanced Parkinson's disease
• Date of first enrolment: 30/05/2016
• Target sample size: 47
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005078-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: rater-blinded study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: 2 dosages of IMP will be studied: Regimen 1 (720mg LD/90mg CD) vs Regimen 2 (537.6mg LD/67.2mg CD) Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Israel, Italy, United States

Contacts

• Name: Yael Ullmann
• Affiliation: NeuroDerm Ltd.

• Name: Yael Ullmann
• Affiliation: NeuroDerm Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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).
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 (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.
5. Subjects must be stable on their anti-PD medication for at least 30 days before Day 1.
6. 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.
7. Must have a minimum of 2.5 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, 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.
12. Willingness and ability to comply with study requirements.
13. Subjects should have a study partner.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
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 or the eligibility reviewer, 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. Subjects who are not willing to operate the pump system.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Subjects with advanced Parkinson's disease
MedDRA version: 19.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: levodopa/carbidopa solution
Product Code: ND0612
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Levodopa
CAS Number: 59-92-7
Current Sponsor code: -
Other descriptive name: LEVODOPA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: Carbidopa
CAS Number: 38821-49-7
Current Sponsor code: -
Other descriptive name: CARBIDOPA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 7.5-

Primary Outcome(s)

Secondary Objective: * To assess the difference between the 2 continuous SC infusion dosing regimens of ND0612H vs. standard oral LD/DDI (Dopa Decarboxylase Inhibitor) treatment on ability to induce early morning full “ON”
* To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on daily “ON” time without dyskinesia and “ON” time with dyskinesia (mild, moderate and severe).
* To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on the motor score and activities of daily living scores of the Unified PD Rating Scale in comparison to standard oral LD/DDI treatment.
* To assess the Clinical Global Impression , Parkinson’s Disease Sleep Scale, and 39-Item PD Quality of Life [QoL] Questionnaire.
* To determine the need for rescue doses/dose modifications/additional therapy of standard oral LD/CD Immediate Release and/or entacapone.
* To profile the pharmacokinetics of 2 dosing regimens of ND0612H compared to the subject’s standard oral LD/DDI dose.

Main Objective: To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on daily “OFF” time

Primary end point(s): The primary endpoint is the change from baseline to Day 28 in daily “OFF” time (i.e. the phase with no response to medication and significant motor symptoms) as assessed by a blinded rater

Timepoint(s) of evaluation of this end point: Day 28

Secondary Outcome(s)

Secondary end point(s): The key secondary efficacy endpoint is the percentage of subjects with full “ON” (i.e. an “ON” response comparable to the “ON” response to standard oral LD/DDI treatment) at approximately 08:00 and approximately 09:00 on Day 28, as determined by the subject and the blinded rater separately.

The other secondary endpoints are:
• Change from baseline to Day 28 in daily “ON” time without dyskinesia and “ON” time with dyskinesia (mild, moderate, severe) as assessed by a blinded rater, with “ON” time defined as phase
with good response to medication and few symptoms.
• Change from baseline to Day 28 in UPDRS part III (motor) scores, at 4 and 8 hrs post dose/infusion start
• Change from baseline to Day 28 in UPDRS part II (ADL) scores
• CGI-Improvement (CGI-I) score on Day 28 and change from baseline to Day 28 in CGI-Severity (CGI-S) score as assessed by investigator
• Change from baseline to Day 27 in PDSS total score
• Change from baseline to Day 27 in PDQ-39 summary index and the 8 dimension scores
• Need for supplemental oral LD/CD and/or entacapone during the outpatient period
• Pharmacokinetics at 2 time points

Timepoint(s) of evaluation of this end point: Day 27 and Day 28

Secondary ID(s)

ND0612H-006

Source(s) of Monetary Support

NeuroDerm Ltd.