advanced Parkinson's disease MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: soluzione di levodopa/carbidopa
Product Code: ND0612
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Current Sponsor code: NA
Other descript
Sponsors
NEURODERM LTD.
Eligibility
Sex/Gender
All
Inclusion 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 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 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, 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 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
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. Prior neurosurgical procedure for PD, or Duodopa treatment. 5. Subjects with a history of drug abuse or alcoholism within the past 12 months. 6. Clinically significant ECG rhythm abnormalities. 7. 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. 8. Subjects who are not willing to operate the pump system.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on daily ¿OFF¿ time.;Secondary Objective: - To assess the difference between the 2 dosing regimens of ND0612H vs. standard oral LD/CD treatment on ability to induce early morning full ¿ON¿. - To assess the effect of 2 dosing regimens of ND0612H on daily ¿ON¿ time without dyskinesia and ¿ON¿ time with dyskinesia . - To assess the effect of 2 dosing regimens of ND0612H on the motor score and activities of daily living (ADL) scores of the Unified Parkinson¿s Disease Rating Scale (UPDRS) in comparison to standard oral LD/CD treatment. - To assess the Clinical Global Impression (CGI; improvement and severity score assessed by investigator), Parkinson¿s Disease Sleep Scale (PDSS), and 39-Item PD Quality of Life [QoL] Questionnaire (PDQ-39). - To determine the need for rescue doses/dose modifications/additional therapy of standard oral LD/CD Immediate Release (IR) and/or entacapone. - To profile the pharmacokinetics (PK) of 2 dosing regimens of ND0612H;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
| Measure | Time frame |
|---|---|
| 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/CD 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 rescue and/or additional oral LD/CD IR 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 | — |
Countries
Austria, Germany, Israel, Italy, United States
Contacts
Public ContactYaell Ullmann
NeuroDerm Ltd.
Outcome results
None listed