Efficacy, Safety and Tolerability Study of ND0612 vs. Oral Immediate Release Levodopa/Carbidopa (IR-LD/CD) in Subjects With Parkinson's Disease Experiencing Motor Fluctuations

Phase 3

Active, not recruiting

Conditions: Parkinson's Disease

Interventions: Combination Product: Placebo for SC infusion
Drug: Oral IR-LD/CD
Combination Product: ND0612 Solution for SC infusion
Drug: Placebo for Oral IR-LD/CD

Registration Number: NCT04006210

Lead Sponsor: NeuroDerm Ltd.

Brief Summary: This is a multi-center, randomized, double-blind, double-dummy, active controlled clinical Study. Following a screening period, eligible subjects will be enrolled to an open-label oral IR-LD/CD adjustment period; then an open-label ND0612 conversion period; then after optimization periods subjects will be randomized to receive either ND0612 or its matching Placebo with IR-LD/CD.

Subjects can continue to an optional open-label extension period.

Detailed Description: This is a phase III multi-center, randomized, active-controlled, double-blind, double-dummy (DBDD), parallel group clinical trial, investigating the efficacy, safety, and tolerability of continuous subcutaneous (SC) ND0612 infusion in comparison to oral IR-LD/CD in subjects with Parkinson's disease (PD) experiencing motor fluctuations.

This study is comprised of 6 periods:

1. a Screening Period;

2. an open-label oral IR-LD/CD Adjustment Period;

3. an open-label ND0612 Conversion Period;

4. a randomized DBDD active-controlled Maintenance Period;

5. an optional open-label Treatment Extension; and

6. a Safety Follow-up Period.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 381

Inclusion Criteria

Male and female patients, aged ≥30 years.
PD diagnosis consistent with the United Kingdom Brain Bank Criteria.
Modiﬁed Hoehn & Yahr score ≤3 during "ON" state.
Average of ≥2.5 hours of OFF time (≥2 hours "OFF" time every day) during waking hours as conﬁrmed by patient diary over 3 days.
Taking ≥4 levodopa doses/day (≥3 doses/day of extended release LD/dopa-decarboxylase inhibitor, e.g., Rytary®) at a total daily dose of ≥400mg.

Exclusion Criteria

Atypical or secondary parkinsonism.
Severe disabling dyskinesias, based on Investigator's discretion.
Previous neurosurgery for PD.
Use of duodenal levodopa infusion (LCIG) or apomorphine infusion.
Use of the following medications: subcutaneous apomorphine injections, sublingual apomorphine, or inhaled levodopa within 4 weeks.
Previous participation in ND0612 studies.
History of signiﬁcant skin conditions or disorders.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IR-LD/CD Group	Placebo for SC infusion	Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
Oral IR-LD/CD Adjustment	Oral IR-LD/CD	Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks.
ND0612 Group	Oral IR-LD/CD	ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 Group	Placebo for Oral IR-LD/CD	ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 Conversion	ND0612 Solution for SC infusion	ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.
IR-LD/CD Group	Placebo for Oral IR-LD/CD	Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
IR-LD/CD Group	Oral IR-LD/CD	Placebo for ND0612 continuous SC infusion + Placebo IR-LD/CD (grey capsules) + Active IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 Group	ND0612 Solution for SC infusion	ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.
ND0612 Conversion	Oral IR-LD/CD	ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.
Open-Label Extension	ND0612 Solution for SC infusion	ND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months.

Primary Outcome Measures

Name	Time	Method
The change in daily ON time without troublesome dyskinesia	Baseline to the end of DBDD Maintenance Period (12 weeks)	ON time without troublesome dyskinesia is the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia per patient diary

Secondary Outcome Measures

Name	Time	Method
The change in daily OFF time	Baseline to the end of DBDD Maintenance Period (12 weeks)	OFF time per patient diary

Trial Locations

Locations (103): Xenoscience
🇺🇸
Phoenix, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Cedar- Sinai Medical Center Department of Neurology
🇺🇸
Los Angeles, California, United States
SC3 Research - Reseda
🇺🇸
Reseda, California, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Rocky Mountain Movement Disorders Center
🇺🇸
Englewood, Colorado, United States
Hartford Healthcare Chase Family Movement Disorders Center
🇺🇸
Vernon, Connecticut, United States
Visionary Investigators Network
🇺🇸
Aventura, Florida, United States
Parkinsons Disease and Movement Disorders Center of Boca Raton
🇺🇸
Boca Raton, Florida, United States
University of Florida Norman Fixel Institute for Neurological Diseases
🇺🇸
Gainesville, Florida, United States
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Xenoscience
🇺🇸Phoenix, Arizona, United States