A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of Six Months Treatment With Ropinirole PR as Adjunctive Therapy in Patients With Parkinson's Disease Who Are Not Optimally Controlled on L-Dopa
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: ReQuip PR; Placebo
Intervention description: If subjects are still eligible at the end of the placebo run-in period they will be randomized (1:1) to receive once daily doses of ropinirole PR or identical appearing placebo tablets. Dosing will start at 2 mg ropinirole PR, or placebo equivalent. During the 24 week treatment phase, the subjects dose will be adjusted according to the recommended schedule to achieve symptomatic control. All subjects must be titrated to a minimum dose of 6 mg/day.; Placebo
Intervention MeSH terms: Ropinirole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 347.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      This is a phase III, multicenter, randomized, double-blind, parallel group,
      placebo-controlled study to compare the efficacy of 6-months therapy of ropinirole Prolonged
      Release (PR) with that of placebo as adjunctive therapy to L-dopa in Parkinson's disease
      patients not optimally controlled on L-dopa. This study will be conducted in China. Subjects
      will have total 14 visits over the 26 week duration of the study.

      Following screening, eligible subjects will receive study medication during the fourteen day
      placebo run-in period which they will be instructed to take in addition to their background
      L-dopa. If subjects are still eligible at the end of the placebo run-in period they will be
      randomized (1:1) to receive once daily doses of ropinirole PR or identical appearing placebo
      tablets. Dosing will start at 2 mg ropinirole PR, or placebo equivalent. During the 24 week
      treatment phase, the subjects dose will be adjusted according to the recommended schedule to
      achieve symptomatic control. All subjects must be titrated to a minimum dose of 6 mg/day. If
      sufficient symptomatic control is not achieved or maintained at a dose of 6mg/day of
      ropinirole PR, the daily dose should be increased by 2mg at weekly or longer intervals up to
      a dose of 8mg/day.If sufficient symptomatic control is still not achieved or maintained at a
      dose of 8mg/day of ropinirole PR, the daily dose should be increased by 4mg at two weekly or
      longer intervals. Further dose titration should not be conducted within the final 8 weeks of
      the treatment phase. The maximum recommended daily dose is 24mg.

      The planned reduction in L-dopa dose will begin once subjects are titrated to Dose Level 4 or
      Dose Level 5 of study medication. For each increase in study medication, there will be a
      corresponding decrease in L-dopa. If loss of symptom control occurs with the reduction in the
      background L-dopa dose, the dose of study medication should be increased to the next higher
      dose level with no adjustment in the dose of L-dopa. If loss of symptom control persists,
      subjects should be titrated up an additional dose level. Subjects who do not experience an
      improvement in symptoms following upward titration by 2 dose levels of study medication,
      should be "rescued" with L-dopa.

      Subjects will be dispensed down-titration medication at the study completion/early withdrawal
      visit if the patient did not enter extension study and should be scheduled to return for a
      follow up visit 4 to 14 days after the last dose of study medication. The extension study aim
      to evaluate the safety profile of ReQuip PR during long-term treatment in subjects with
      advanced parkinson's disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or non-pregnant/non-breast-feeding women of at least 30 years of age at
             screening.Women of child-bearing potential must be practicing a clinically accepted
             method of contraception (such as oral contraception, surgical sterilization,
             intrauterine device [IUD], or diaphragm IN ADDITION to spermicidal foam and condom on
             male partner, or systemic contraception [i.e. Norplant System]), during the study and
             for at least one month prior to randomisation and one month following completion of
             the study.

          -  Diagnosis of idiopathic Parkinson's Disease (according to modified Hoehn & Yahr
             criteria Stages II-IV) and demonstrating lack of control with L-dopa therapy (e.g. end
             of dose akinesia, simple on/off fluctuations)

          -  Subjects receiving a stable dose of L-dopa for at least four weeks prior to screening.

          -  Provide written informed consent for this study

          -  A minimum of 3 hours awake time"off " for each diary day recorded during the Placebo
             Run-In Period.

          -  Be willing and able to comply with study procedures, including diary card completion
             and follow-up clinic visits.

        Exclusion Criteria:

          -  Late stage advanced subjects demonstrating incapacitating peak dose or biphasic
             dyskinesia on their stable dose of L-dopa.

          -  Presence, or history within the previous 3 months, of significant and/or uncontrolled
             psychiatric, hematological, renal, hepatic, endocrinological, neurological (other than
             Parkinson.s Disease), or cardiovascular disease or active malignancy (other than basal
             cell cancer);

          -  Any abnormality, at Screening, that the investigator deems to be clinically relevant
             on history, physical examination and in diagnostic laboratory tests including ECG;

          -  Unstable liver disease, cirrhosis, known biliary abnormalities(except Gilbert's
             syndrome or asymptomatic gallstones) or AST or ALT>2xULN or alk phos and bilirubin>1.5
             xULN

          -  Recent history of severe dizziness or fainting due to postural hypotension on
             standing.

          -  Clinical dementia that in the judgment of the investigator would preclude assessment
             of the subject.

          -  Recent history or current evidence of drug abuse or alcoholism.

          -  Consumption of any dopamine agonist within four weeks of the screening visit.

          -  Definite or suspected personal or family history of clinically significant adverse
             reactions or hypersensitivity to ropinirole (or to drugs with a similar chemical
             structure) that would preclude long-term dosing with ropinirole PR.

          -  Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any
             drug known to substantially inhibit CYP1A2 (e.g. ciprofloxacine, fluvoxamine,
             cimetidine, ethinyloestradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7
             days prior to enrolment. Subjects already on chronic therapy with any of these agents
             may be enrolled but must remain on stable doses of the agent from 7 days prior to
             enrolment through the end of the Treatment Period.

          -  Use of an investigational drug within 30 days or 5 half-lives (which ever is longer).