Infusion of Apomorphine: Long-term Safety Study

Study Overview
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Brief Summary
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This is a Phase 3, multicenter, open-label, safety and tolerability study of continuous apomorphine infusion in subjects with advanced Parkinson's Disease (PD) whose motor fluctuations remain unsatisfactory with levodopa (or levodopa/carbidopa) and at least one other class of drugs or mode of therapy for PD.

Detailed Description
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This Phase 3, multicenter, open-label study will assess the long-term safety and tolerability of continuous subcutaneous infusion of apomorphine in advanced Parkinson's disease (PD) patients whose motor fluctuations remain unsatisfactory with levodopa (or levodopa/carbidopa) and at least one other class of drugs or mode of therapy for PD. Further, this study will assess the clinical effectiveness of continuous apomorphine subcutaneous infusion in reducing off time in advanced PD patients and to assess the clinical effectiveness of continuous subcutaneous infusion of apomorphine in improving on time without resulting in an increase in troublesome dyskinesias.

Official Title
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A Phase 3, Open-Label Study of the Safety, Efficacy and Tolerability of Apomorphine Administered by Continuous Subcutaneous Infusion in Advanced Parkinson's Disease Patients With Unsatisfactory Control on Available Therapy

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: apomorphine infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced idiopathic PD consistent with UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria Overall motor control is unsatisfactory in the opinion of the Investigator and subject despite optimized treatment with available therapies, which must include a stable regimen of daily maintenance levodopa (or levodopa/carbidopa), and at least one of the following other classes of therapies: Dopamine agonists (note: APOKYN intermittent injection is not to be considered here) Monoamine oxidase B [MAO B] inhibitors Catechol-O-methyltransferase (COMT) inhibitors Deep brain stimulation (DBS) Levodopa/carbidopa intestinal gel surgery (Duopa, Duodopa) Other - amantadine at doses of up to 400 mg per day) Experiences off periods averaging ≥3.0 hours per waking day Other criteria will be discussed in detail with potential subjects by site Investigator Exclusion Criteria: Planned surgical intervention for the treatment of Parkinson's disease during participation in the study History of hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN PFS, including sodium metabisulfite Known, suspected, or planned pregnancy or lactation. Recent history (within the previous 12 months) of alcohol or substance abuse History of impulsive/compulsive behaviors primarily associated with the use of dopamine agonists History of previously treated or current diagnosis of malignant melanoma Exhibits certain signs and symptoms of cardiovascular disease Other criteria will be discussed in detail with potential subjects by site Investigator

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apomorphine infusion<br>Continuous subcutaneous apomorphine infusion | Drug: apomorphine infusion<br>* Treatment with apomorphine provided by continuous subcutaneous infusion using a portable external electronic pump device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of daily off time during the waking day |  | Baseline Visit to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent daily on time without troublesome dyskinesias during waking day |  | Baseline Visit to Week 12 | 
| Percent of daily off time during the waking day |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Percent of daily on time without troublesome dyskinesias during the waking day |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Percent of daily on time without dyskinesias |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Unified Parkinson's Disease Rating Scale - Motor Score |  | Baseline Visit to Week 12 | 
| Clinical Global Impression of Severity (CGI-S) and Change (CGI-C) Scale |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Patient Global Impression of Severity (PGI-S) and Change (PGI-C) Scale |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Parkinson's Disease Questionnaire |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| United Parkinson's Disease Rating Scale - Activities of Daily Living Score |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Proportion of responders |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 
| Frequency and total dose of average daily intermittent injection APOKYN for subjects on APOKYN treatment at study entry |  | Baseline Visit to Treatment Weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all Treatment Extension Period Visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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off, Parkinson's disease,, apomorphine, Apokyn, dopamine agonist, levodopa, advanced, PD, carbidopa, pramipexole, ropinirole, rotigotine, MAO-B inhibitors, COMT inhibitors, dyskinesia