Relative Bioavailability Study of Ropinirole Implants in Parkinson's Patients on L-Dopa Switched From Oral Ropinirole

Study Overview
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Brief Summary
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Subjects stable on L-Dopa and oral ropinirole will have their ropinirole replaced with the Ropinirole Implant(s). The Ropinirole Implant was designed using the ProNeura™ implant technology where the implant is inserted under the skin. This study will measure how much ropinirole is released in the blood during 12 weeks of ropinirole implant treatment, and evaluate the side effects of this new formulation.

Official Title
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An Open-Label, Relative Bioavailability Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ropinirole Implants in Patients With Parkinson's Disease Switched From Oral Immediate-Release Ropinirole While on L-Dopa

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Ropinirole oral product
* Drug: Ropinirole Implant


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Voluntarily provided informed consent Meet diagnostic criteria for idiopathic Parkinson's Disease On L-Dopa and oral ropinirole If female of child-bearing potential, willing to practice contraception from time of informed consent to Follow-Up Visit Key Exclusion Criteria: Pregnant, breastfeeding, or planning to become pregnant Active epilepsy within the past year Severe dementia or cognitive impairment Donated or lost > 400 mL of blood within 1 month prior to Screening History of alcohol or substance use disorder within the prior 12 months Recent episodes of moderate to severe dizziness or syncope Definite or suspected hypersensitivity to ropinirole or ethylene vinyl acetate Used any other investigational drug within 60 days or 5 half-lives prior to Screening, or plan to take any such drug any time during the study

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects receive oral immediate release (IR) ropinirole for 7-10 days, and then are switched to ropinirole implant(s) for 12 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Requip; One Ropinirole Implant | Drug: Ropinirole oral product<br>* oral immediate-release ropinirole<br>* Other names: Requip;Drug: Ropinirole Implant<br>* ropinirole hydrochloride/ethylene vinyl acetate<br>|
| Experimental: Cohort 2<br>Requip; Two Ropinirole Implants | Drug: Ropinirole oral product<br>* oral immediate-release ropinirole<br>* Other names: Requip;Drug: Ropinirole Implant<br>* ropinirole hydrochloride/ethylene vinyl acetate<br>|
| Experimental: Cohort 3<br>Requip; Three Ropinirole Implants | Drug: Ropinirole oral product<br>* oral immediate-release ropinirole<br>* Other names: Requip;Drug: Ropinirole Implant<br>* ropinirole hydrochloride/ethylene vinyl acetate<br>|
| Experimental: Cohort 4<br>Requip; Four Ropinirole Implants | Drug: Ropinirole oral product<br>* oral immediate-release ropinirole<br>* Other names: Requip;Drug: Ropinirole Implant<br>* ropinirole hydrochloride/ethylene vinyl acetate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24 Hours of Ropinirole | Area under the plasma drug concentration-time curve of ropinirole | 0-24 hours | 
| Total Number of Adverse Events Across Participants | Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population. | 0-12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24 Hours of N-despropyl Ropinirole | Area under the plasma drug concentration-time curve of N-despropyl ropinirole | 0-24 hours | 
| AUC0-24 Hours of 7-hydroxy Ropinirole | Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole | 0-24 hours | 
| Mean Change From Baseline in MDS-UPDRS Total Score | Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome. | Baseline and Weeks 4, 8 and 12 | 
| Mean Change From Baseline of Awake Time On | Efficacy of ropinirole implants presented as mean change from baseline of awake time on. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). On refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days. | Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12 | 
| Mean Change From Baseline of Awake Time Off | Efficacy of ropinirole implants presented as mean change from baseline of awake time Off. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). Off refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days | Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Dyskinesia, ropinirole, implant, ProNeura, movement disorders, dopamine agonist, extended-release, Parkinsonian disorders, brain diseases, central nervous system diseases, Neurodegenerative Diseases, Antiparkinson agents, Anti-dyskinesia agents, dopamine agents, neurotransmitter agents, REQUIP, subdermal