A Clinical Study Investigating the Efficacy, Tolerability, and Safety of Continuous Subcutaneous ND0612 Infusion Given as Adjunct Treatment to Oral Levodopa in Patients With Parkinson's Disease With Motor Fluctuations

Phase 3

Withdrawn

• Conditions: Parkinson's Disease
• Interventions: Drug: ND0612; Drug: Placebo

• Registration Number: NCT02782481
• Lead Sponsor: NeuroDerm Ltd.

Brief Summary

This is a multicenter, randomized, double blind, placebo controlled parallel group clinical study. Following a screening period of up to 28 days, eligible subjects will be randomized to receive adjunct treatment to oral LD/DDI (Dopa Decarboxylase Inhibitor) with continuous subcutaneous infusion of ND0612 or matching placebo for 16 weeks.

Detailed Description

This phase III randomized, double-blind, placebo controlled, parallel group clinical study will be conducted in 150 subjects with idiopathic PD who are experiencing motor complications despite optimized anti-PD therapy.

The study will investigate the efficacy, safety and tolerability of continuous SC infusion (16 weeks) of ND0612 compared with placebo infusion. The treatment period will be comprised of a 4-week adjustment period during which time the ND0612 infusion dose will remain constant and the oral LD/DDI dose can be decreased or increased back up to the Baseline levels. All other anti-PD treatments must remain constant. During the maintenance period (Weeks 5 to 16) all anti-PD medication including the ND0612/placebo should remain constant.

Study Timeline

• Study First Submitted: 2016-05-22
• Study First Submitted QC: 2016-05-22
• Study First Posted: 2016-05-25
• Study Start: 2016-08
• Primary Completion: 2018-10-15
• Study Completion: 2018-10-15
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-09
• Last Update Posted: 2019-12-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Male and female PD subjects of any race aged 30-80 years
2. PD diagnosis consistent with the UK Brain Bank Criteria.
3. Modified Hoehn & Yahr scale in "ON" state ≤3
4. Subjects must experience motor fluctuations and experience an average of at least 2 hours daily in the "OFF" state
5. Taking at least 4 doses/day of IR LD/DDI (or at least 3 doses/day of Rytary) and taking, or having taken therapeutic doses of at least 2 other classes of anti-PD medications.
6. Subjects must be on stable doses of all their anti-PD medications for at least 28 days before Baseline (Day 1).
7. Subject and/or study partner must demonstrate ability to keep accurate diary entries of PD symptoms ("ON-OFF" diaries) with at least 75% concordance with the study rater by the end of the diary training session at the end of the screening period.
8. Mini Mental State Examination (MMSE) score >26.
9. 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.

Key

Exclusion Criteria

1. Atypical or secondary parkinsonism.
2. Psychosis or hallucinations in past 6 months.
3. Subjects with a clinically significant or unstable medical, surgical, psychiatric condition or laboratory abnormalities which, in the opinion of the Investigator or the EAC, represents a safety risk, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
4. Clinically significant ECG abnormalities.
5. Renal or liver dysfunction that may alter drug metabolism including Screening visit serum levels of creatinine >1.3 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x upper limit of normal (ULN), total bilirubin >2.5 mg/dL.
6. Positive serum serology for Hepatitits B Virus (HBV), Hepatitits C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit
7. 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
8. Use of prohibited medications as per protocol
9. Subjects who have previously undergone treatment for PD with a neurosurgical intervention (e.g., pallidotomy, thalamotomy, transplantation, deep brain stimulation procedures), Duodopa/Duopa, or continuous dopaminergic or apomorphine infusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ND0612 High dose (Levodopa/Carbidopa solution)	ND0612	High dose ND0612 SC infusion over 24 h
ND0612 Low dose (Levodopa/Carbidopa solution)	ND0612	Low dose ND0612 SC infusion over 24 h
Placebo	Placebo	Placebo SC infusion over 24 h

Primary Outcome Measures

Name	Time	Method
The change from Baseline to Week 16 in the mean percentage of "OFF" time during waking hours, based on patient's home diary assessments	baseline to week 16

Trial Locations

Locations (1)

Haddasah Ein Kerem Medical center; 🇮🇱 Jerusalem, Israel