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

Study Overview
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Brief Summary
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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
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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: a Screening Period; an open-label oral IR-LD/CD Adjustment Period; an open-label ND0612 Conversion Period; a randomized DBDD active-controlled Maintenance Period; an optional open-label Treatment Extension; and a Safety Follow-up Period.

Official Title
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A Multicenter, Randomized, Active-controlled, Double-blind, Double-dummy, Parallel-group Clinical Trial, Investigating the Efficacy, Safety, and Tolerability of Continuous Subcutaneous ND0612 Infusion in Comparison to Oral IR-LD/CD in Subjects With Parkinson's Disease Experiencing Motor Fluctuations (BouNDless)

Conditions
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Parkinson's Disease

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Oral IR-LD/CD Adjustment Period - Run-in 1 (1 arm) followed by ND0612 Conversion Period - Run-in 2 (1 arm) followed by DBDD Parallel Group Maintenance Period (2 arms) followed by optional Open-label Extension Period (1 arm)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ND0612 Group<br>ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks. | Combination Product: ND0612 Solution for SC infusion<br>* Levodopa/Carbidopa (LD/CD) solution administered SC via infusion pump<br>Drug: Oral IR-LD/CD<br>* Encapsulated LD/CD 100mg/25mg<br>* Other names: IR-LD/CD;Drug: Placebo for Oral IR-LD/CD<br>* Encapsulated Placebo for LD/CD 100mg/25mg<br>* Other names: Placebo for IR-LD/CD;|
| Active Comparator: IR-LD/CD Group<br>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. | Combination Product: Placebo for SC infusion<br>* Placebo solution administered SC via infusion pump<br>Drug: Oral IR-LD/CD<br>* Encapsulated LD/CD 100mg/25mg<br>* Other names: IR-LD/CD;Drug: Placebo for Oral IR-LD/CD<br>* Encapsulated Placebo for LD/CD 100mg/25mg<br>* Other names: Placebo for IR-LD/CD;|
| Other: Oral IR-LD/CD Adjustment<br>Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks. | Drug: Oral IR-LD/CD<br>* Encapsulated LD/CD 100mg/25mg<br>* Other names: IR-LD/CD;|
| Other: ND0612 Conversion<br>ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks. | Combination Product: ND0612 Solution for SC infusion<br>* Levodopa/Carbidopa (LD/CD) solution administered SC via infusion pump<br>Drug: Oral IR-LD/CD<br>* Encapsulated LD/CD 100mg/25mg<br>* Other names: IR-LD/CD;|
| Other: Open-Label Extension<br>ND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months. | Combination Product: ND0612 Solution for SC infusion<br>* Levodopa/Carbidopa (LD/CD) solution administered SC via infusion pump<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in daily OFF time | OFF time per patient diary | Baseline to the end of DBDD Maintenance Period (12 weeks) |