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

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

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.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Ropinirole oral product; Drug: Ropinirole Implant

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando, Florida
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Farmington Hills, Michigan
  • Washington
    • Kirkland, Washington, United States, 98034
      • Kirkland, Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Actual): May 22, 2018
• Study Completion (Actual): May 22, 2018

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson Disease; movement disorders; Neurodegenerative Diseases; brain diseases; dopamine agonist; implant; Dyskinesia; ropinirole; ProNeura; extended-release; Parkinsonian disorders; central nervous system diseases; Antiparkinson agents; Anti-dyskinesia agents; dopamine agents; neurotransmitter agents; REQUIP; subdermal
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Ropinirole
• Other Study ID Numbers: ROP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No