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

• Ropinirole oral product (Drug), also known as Requip: oral immediate-release ropinirole
• Ropinirole Implant (Drug): ropinirole hydrochloride/ethylene vinyl acetate

Primary outcomes

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

Secondary outcomes

• AUC0-24 Hours of N-despropyl Ropinirole [0-24 hours]: Area under the plasma drug concentration-time curve of N-despropyl ropinirole
• AUC0-24 Hours of 7-hydroxy Ropinirole [0-24 hours]: Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole
• Mean Change From Baseline in MDS-UPDRS Total Score [Baseline and Weeks 4, 8 and 12]: 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.
• Mean Change From Baseline of Awake Time "On" [Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12]: 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.
• Mean Change From Baseline of Awake Time "Off" [Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12]: 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

Sex: All, ages: 30 Years to 80 Years

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

Participant flow

Outcome results

• AUC0-24 Hours of Ropinirole (Primary)
• Total Number of Adverse Events Across Participants (Primary), Number, Events: Cohort 1 4
• AUC0-24 Hours of N-despropyl Ropinirole (Secondary)
• AUC0-24 Hours of 7-hydroxy Ropinirole (Secondary)
• Mean Change From Baseline in MDS-UPDRS Total Score (Secondary), Mean, units on a scale: Cohort 1 4.0 +/- 3.28
• Mean Change From Baseline of Awake Time "On" (Secondary), Mean, hours: Cohort 1 0.80 +/- 1.078
• Mean Change From Baseline of Awake Time "Off" (Secondary), Mean, hours: Cohort 1 -1.36 +/- 0.974

Adverse events

Time frame: From signing of the ICF until 30 days following study drug treatment discontinuation, up to 22 weeks.

Other adverse events by term

Limitations and caveats: This was a first-in-human study of ropinirole implants. The trial was terminated early at the request of the Sponsor, not for reasons of safety or efficacy.

• Study Protocol (PDF, 2017-06-07)
• Statistical Analysis Plan (PDF, 2018-05-11)

• Dr. Kate Beebe DeVarney, Study director, Titan Pharmaceuticals