A Safety, Tolerability, and Pharmacokinetic Study of ND0612 Delivered as a Continuous Subcutaneous in Parkinson's Disease Patients

A Multicenter, Open-Label, Randomized, Dose-Finding Study Testing the Safety, Tolerability, and Pharmacokinetics (PK) of ND0612, a Liquid Formulation of Levodopa/Carbidopa (LD/CD) Delivered as a Continuous Subcutaneous Infusion (SC) in Parkinson's Disease (PD) Patients Treated With LD

An open-label randomized study to evaluate the Safety, Tolerability, and PK of Low and High single doses of ND0612 (i.e. LD/CD ratio 60/7.5 mg/mL and 60/14 mg/mL), as well as the combination with oral Entacapone (concomitant catechol-O-methyl transferase [COMT] inhibitor) in PD subjects with well-defined morning "OFF" and a good response to LD. Exploratory efficacy parameters were collected (early evidence of effectiveness as part of Phase 1).

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: LD/CD SC solution; Drug: Entacapone

Detailed Description

PD subjects were randomized in Low or High LD dose study group in 1:1 ratio. Each patient received singe doses ND0612 over 3 days: Day 1. LD/CD 60/7.5 mg/mL, Day 2. LD/CD 60/14 mg, and Day 3. LD/CD 60/14 mg/mL with Entacapone.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female PD patients of any race aged 30 to 80 years
2. PD diagnosis consistent with the UK PD Society Brain Bank criteria.
3. Stable doses of anti PD drugs for at least 30 days
4. PD patients with well-defined morning "OFF" and a good response to LD
5. MMSE score > 26
6. No clinically significant medical, psychiatric or laboratory abnormalities

Exclusion Criteria:

1. Atypical or secondary Parkinsonism.
2. Acute psychosis or hallucinations.
3. Subjects treated with neuroleptics
4. History of melanoma or significant skin disorders.
5. Prior neurosurgical procedure for PD.
6. Patients with a history of drug abuse or alcoholism
7. Clinically significant ECG abnormalities.
8. Renal or liver dysfunction
9. Subjects who have participated in another clinical study within 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ND0612L Low LD Dose; LD daily dose equals to 115 mg administered over 8 hours SC infusion: LD/CD 60/7.5 mg/mL on Study Day 3; LD/CD 60/14 mg/mL on Study Day 4; LD/CD 60/14 mg/mL and Entacapone 200 mg every 4 hours on Study Day 5	Drug: LD/CD SC solution; Levodopa/carbidopa SC solution; Other Names: ND0612; Drug: Entacapone; Entacapone 200 mg oral tablet
Experimental: ND0612H High LD Dose; LD daily dose equals to 307 mg administered over 8 hours SC infusion: LD/CD 60/7.5 mg/mL on Study Day 3; LD/CD 60/14 mg/mL on Study Day 4; LD/CD 60/14 mg/mL and Entacapone 200 mg every 4 hours on Study Day 5	Drug: LD/CD SC solution; Levodopa/carbidopa SC solution; Other Names: ND0612; Drug: Entacapone; Entacapone 200 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events frequency	Up to 6 weeks
LD, CD and 3-OMD PK analysis from sample taken on Days 3, 4 and 5 will be used to determine the Fluctuation Index, its CV, AUC, Cmin, Cmax, and tmax.	Days 1, 2, 3 and 4
Tolerability: Number of patients who discontinued due to adverse events	Up to 6 weeks

Collaborators and Investigators

• Sponsor: NeuroDerm Ltd.
• Collaborators: Michael J. Fox Foundation for Parkinson's Research

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2014
• Primary Completion (Actual): March 15, 2015
• Study Completion (Actual): March 15, 2015

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 23, 2014
• First Posted (Estimated): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Motor fluctuations; levodopa pharmacokinetics; levodopa and carbidopa solution; continuous subcutaneous delivery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Entacapone
• Other Study ID Numbers: ND0612/004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No