Post-marketing study of ropinirole prolonged release tablets in Parkinson’s disease: Evaluation outcomes associated with long term use of Ropinirole-PR using the clinical practice research datalink (CPRD) (111981)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N04BC) Dopamine agonists

  Dopamine agonists
• Medical condition to be studied:
  Parkinson's disease

Population studied

• Short description of the study population:
  The populations of interest comprised of individuals on the CPRD with a recorded Parkinson’s disease diagnosis that had initiated either ropinirole-PR monotherapy (ropinirole-PR) or an oral immediate release dopamine agonist (IR-DA) as monotherapy between 2008 and 2013.; ; Inclusion criteria:; Individuals were required to; - Meet the case definition of Parkinson’s disease; - Have initiated a dopamine agonist therapy between 2008-2013 and received at least two prescriptions for the therapy of interest.; - Have a minimum of 12 months of registration prior the date of initiation of the dopamine agonist therapy +30 days in order to collect information on disease,; comorbidity, medical and prescription history.; - Belong to practices that are considered up to research standard at initiation of therapy.; ; Exclusion criteria; - Individuals in the immediate release dopamine agonist cohort that had previously been prescribed any prolonged release dopamine agonist (ropinirole-PR or; pramipexole-PR) were excluded.; - Individuals with evidence of adjunctive or prior history of levodopa use at time of initiating the dopamine agonist therapy were excluded, as were individuals with a history of dyskinesia or impulse control disorders prior to index date.; - Individuals with evidence of secondary or drug induced PD; - Aged <40 years at the time of PD diagnosis
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Parkinson's disease patients
• Estimated number of subjects:
  2000

Study design details

• Main study objective:
  To estimate, the incidence of dyskinesia in PD patients initiating ropinirole-PR monotherapy vs. immediate release dopamine agonist monotherapy. Other outcomes of interest are on-off phenomena (subject to feasibility) and impulse control disorders.
• Outcomes:
  Dyskinesia is the primary outcome. Additional outcomes are impulse control behaviors (ICD) and on-off phenomena. Dyskinesia and ICD will be identified using READ codes on the CPRD supplemented by GP questionnaire. On-off phenomena will be identified solely byGP questionnaire, however, it may not be feasible or appropriate to evaluate this as an outcome should the GP response rate be low, Treatment persistence and adherence will be evaluated. Additionally time to levodopa initiation will be estimated. As levodopa is associated with dyskinesias, delay in its use may further reduce the risk of the development of motor complications, or reflect better control of PD symptoms by current therapy. The extent of off-label use of ropinirole-PR will be described.
• Data analysis plan:
  The incidence of dyskinesia (and other outcomes of interest) will be calculated in the ropinirole-PR and propensity score matched IR-DA cohorts. Censoring occurs at the earliest of an outcome of interest, discontinuation of therapy+30days, end of a patient record or end of the study period. Crude incident rates per 1000 person years of follow-up for each outcome will be calculated. Incidence rates will be stratified by age group (at index date) and PD duration. Incidence rate ratios will be estimated between the exposure groups and adjusted for risk factors using multivariable Poisson regression. In addition, the incidence amongst switchers to ropinirole-PR and those initiating ropinirole-PR de novo will be estimated. A Cox proportional hazards regression model will be used to evaluate time to dyskinesias in individuals in both cohorts. Adjusted hazards ratios will be estimated, accounting for potential confounders and time varying covariates.

Documents

Study results

gsk-111981-clinical-study-report-redact