Post-marketing study of ropinirole prolonged release tablets in Parkinson's disease: Evaluation outcomes associated with long term use of Ropinirole-PR using the UK clinical practice research datalink (UK-CPRD)

Date of Approval: 
2016-03-31 00:00:00
Lay Summary: 
Parkinson's disease (PD) is a progressive neurological condition which results in the deficiency of dopamine, a chemical messenger. Ropinirole is a dopamine agonist which works by mimicking the effects of dopamine and stimulates dopamine receptors. Ropinirole has been marketed for the treatment of PD for over fifteen years and shown to be well tolerated and effective. The proposed observational database study is required as part of a post marketing regulatory commitment to the Medicines and Healthcare products Regulatory Agency (MHRA) to evaluate the long term safety of the prolonged release formulation of ropinirole (ropinirole-PR). It is proposed to estimate the rate of new cases of dyskinesias (involuntary movements), on-off phenomena (a switch between mobility and immobility) and impulse control disorders, in PD patients initiating ropinirole-PR monotherapy as compared to those initiating an immediate release dopamine agonist as monotherapy. The study will use data recorded in the UK Clinical Practice Research Datalink (CPRD) supplemented with data to be obtained by General Practitioner (GP) questionnaires.
Technical Summary: 
This retrospective observational study will use a propensity score matched cohort design to estimate the incidence of dyskinesias, on-off phenomena and impulse control disorders amongst PD patients initiating ropinirole-PR monotherapy (ropinirole-PR cohort) compared to those initiating immediate release dopamine agonist monotherapy(IR-DA cohort). PD patients with at least one script of a dopamine agonist of interest (ropinirole-PR or an immediate release DA) prescribed between 2004-2012 and a minimum of 12 months registration prior to index date (date of treatment initiation) will be included. The incidence dyskinesia and other outcomes of interest events after the index date will be estimated in the ropinirole-PR cohort compared to the matched IR-DA cohort. Adjusted incidence rate ratios will be calculated using multivariable Poisson regression. A Cox proportional hazards regression model will evaluate time to dyskinesias in individuals prescribed ropinirole-PR with those prescribed immediate release dopamine agonists of interest with adjustments for time varying covariates. In addition, time to levodopa initiation in both cohorts will be estimated. Whilst some outcome data are available on the CPRD, it is necessary to supplement this with information to be obtained by GP questionnaire. Patients will be followed up to a maximum of 5 years of treatment. As part of these activities, treatment persistence and adherence will be evaluated as well as off-label use of ropinirole-PR.
Health Outcomes to be Measured: 
All investigators are employed by and hold stocks and shares in GSK
Application Number: 

Usha Gungabissoon - Chief Investigator - GSK
Usha Gungabissoon - Corresponding Applicant - GSK
John Logie - Collaborator - GlaxoSmithKline - UK
Monika. Stender - Collaborator - GlaxoSmithKline - UK
Nicholas Galwey - Collaborator - GSK