Clinical trial NCT02577523: A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease
Official title: A Multicenter, Parallel-group, Rater-blinded, Randomized Clinical Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of 2 Dosing Regimens of ND0612H [ ] in Subjects With Advanced Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: NeuroDerm Ltd.
Sponsor class: INDUSTRY
First posted: 2015-10-16
Enrollment: 38
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This phase IIa randomized, controlled, parallel-group study will be conducted in 36 subjects with advanced PD who are treated with oral LD/CD at a stable dose and have predictable morning "OFF" periods and at least 2.5 hrs of daily "OFF" periods. The study will investigate the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H. Regimen 1 will employ continuous infusion for 24 hrs using a low infusion rate at night and a higher rate at daytime with supplemental administration of oral immediate release (IR) LD/CD in the mornings. During the inpatient period of about 3 days, the site staff will manage the administration and replacement of the infusions. On Day 4 subjects will be discharged home after they and their study partners have received training on the administration of the infusion. Subjects will then continue on a maintenance dose of the assigned ND0612 dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug.

Eligibility 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

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.

Primary outcomes:
measure: Change in Daily "OFF" Time
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: The Percentage of Subjects With Full "ON" at Approximately 08:00 and Approximately 09:00, as Determined by the Subject
timeFrame: Baseline to Day 28
measure: Change in Daily "Good ON" Time as Assessed by a Blinded Rater
timeFrame: Baseline to Day 28
measure: Change in Morning UPDRS Part III (Motor) Scores
timeFrame: Baseline to Day 28
measure: Change in UPDRS Part II (ADL) Scores
timeFrame: Baseline to Day 28
measure: CGI-Improvement (CGI-I) Score as Assessed by Investigator
timeFrame: Baseline to Day 28
measure: Change in PDSS-2 Total Score
timeFrame: Baseline to Day 27
measure: Change in PDQ-39 Summary Index and the 8-dimension Scores
timeFrame: Baseline to Day 27
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Chieti
country: Italy
facility: University Foundation
city: Pisa
country: Italy
facility: AOU Pisa
city: Rome
country: Italy
facility: IRCCS San Raffaele Pisana
city: Venice
country: Italy
facility: Fondazione Ospedale San Camillo - I.R.C.C.S.
Study officials:
affiliation: NeuroDerm Ltd.
name: Laurence Salin, MD
role: STUDY_DIRECTOR
References:
citation: 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.