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

A Clinical Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of ND0612H, a Solution of Levodopa/Carbidopa Administered as a Continuous Subcutaneous Infusion in Subjects With Advanced Parkinson's Disease

Sponsors

Lead sponsor: NeuroDerm Ltd.

Source NeuroDerm Ltd.
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. A safety visit will be performed 4 weeks after the last SC administration of the study drug.

Overall Status Completed
Start Date November 2015
Completion Date January 2017
Primary Completion Date December 2016
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from baseline to Day 28 in daily "OFF" time Baseline to Day 28
Enrollment 38
Condition
Intervention

Intervention type: Drug

Intervention name: ND0612 (Levodopa/Carbidopa solution)

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.

Gender: All

Minimum age: 30 Years

Maximum age: 80 Years

Healthy volunteers: No

Location
facility
Northwestern University | Chicago, Illinois, 60611, United States
QUEST Research Institute | Farmington Hills, Michigan, 48334, United States
Medical University Innsbruck | Innsbruck, A- 4060, Austria
Rabin Medical Center | Petah Tikva, 4941492, Israel
Chaim Sheba Medical Center | Ramat Gan, 56520, Israel
Sourasky Medical Center | Tel Aviv, 64239, Israel
IRCCS San Raffaele Pisana | Rome, 00163, Italy
Fondazione Ospedale San Camillo - I.R.C.C.S. | Venice, 30126, Italy
Location Countries

Austria

Israel

Italy

United States

Verification Date

March 2018

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1

Arm group type: Experimental

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

Arm group label: ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2

Arm group type: Experimental

Description: Dosing Regimen 2 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 14 hours

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov