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 (BouNDless)

NeuroDerm

Status and phase: Active, not recruiting; Phase 3

Conditions: Parkinson's Disease

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04006210

ND0612-317

Details and patient eligibility

About

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.

Full 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.

Enrollment: 381 patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male and female patients, aged ≥30 years.
2. PD diagnosis consistent with the United Kingdom Brain Bank Criteria.
3. Modified Hoehn & Yahr score ≤3 during "ON" state.
4. 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.
5. 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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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381 participants in 5 patient groups

ND0612 Group

Experimental group

Description:

ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules) + Placebo IR-LD/CD (white capsules). Randomized DBDD Maintenance Treatment for 12 weeks.

Treatment:

Drug: Oral IR-LD/CD

Drug: Placebo for Oral IR-LD/CD

Combination Product: ND0612 Solution for SC infusion

IR-LD/CD Group

Active Comparator group

Description:

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.

Treatment:

Combination Product: Placebo for SC infusion

Drug: Oral IR-LD/CD

Drug: Placebo for Oral IR-LD/CD

Oral IR-LD/CD Adjustment

Other group

Description:

Active IR-LD/CD (white capsules). Open-label Treatment in Run-in 1 for 4-6 weeks.

Treatment:

Drug: Oral IR-LD/CD

ND0612 Conversion

Other group

Description:

ND0612 continuous SC infusion + Active IR-LD/CD (grey capsules). Open-label Treatment in Run-in 2 for 4-6 weeks.

Treatment:

Drug: Oral IR-LD/CD

Combination Product: ND0612 Solution for SC infusion

Open-Label Extension

Other group

Description:

ND0612 continuous SC infusion + Standard of care LD/dopa-decarboxylase inhibitor. Open-label Treatment in Extension for up to 54 months.

Treatment:

Combination Product: ND0612 Solution for SC infusion