A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Ropinirole CR 2mg tablet; Ropinirole CR 8mg tablet; Ropinirole CR matching Placebo tablet
Intervention description: Ropinirole CR 2mg tablets will be supplied as white oval film-coated tablets.; Ropinirole CR 8mg tablets will be supplied as white oval film-coated tablets.; Ropinirole CR matching Placebo tablet tablets (containing no active ingredients) indistinguishable in appearance from Ropinirole CR 2 mg tablets.
Intervention MeSH terms: Ropinirole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 81.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Ropinirole; Parkinson's disease

Summary:

      This study is a Phase III, multicentre, randomized, initial double-blind study with
      subsequent open label phases. The study will havea screening phase (4 weeks), a dose increase
      effect verification phase (12 weeks), a down titration 1 phase (1 week), a long-term phase
      (39 weeks), down titration 2 phase (1 to 2 weeks) and a follow up phase. Subjects will be
      assigned to Ropinirole CR high-dose group or Ropinirole CR maintenance group at a ratio of
      3:1. This study is being conducted to evaluate the efficacy (effect of increasing Ropinirole
      dose from 16 mg/day to 18-24 mg/day) of the Ropinirole CR tablets in early and advanced PD
      patients who have not achieved an optimal therapeutic response with marketed Ropinirole
      Immediate release (IR) (15 mg/day) or marketed Ropinirole CR (16 mg/day) formulations.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion criteria at the start of the screening

          -  Patients who are diagnosed as Parkinson's Disease with severity of the modified Hoehn
             & Yahr criteria Stages I-IV.

          -  1) Monotherapy subject: Subjects who have never received L-dopa, or subjects who have
             had prior exposure to L-dopa (up to 450 milligram (mg)/day) for up to 3 months in
             total and L-dopa treatment has been discontinued, for a minimum of 4 weeks prior to
             the screening phase. 2) L-dopa adjunct subject: Subjects receiving L-dopa (up to 450
             mg/day) for at least 4 weeks prior to the screening phase.

          -  Patients receiving 15mg/day Ropinirole IR or 16mg/day Ropinirole CR for 4 weeks prior
             to the screening phase, UPDRS Part III total (on) scores is 10 points or more at
             screening visit and can expect clinical efficacy by increasing Ropinirole CR.

          -  Age: 20years or older (at the time of informed written consent)

          -  Informed consent: Patients who are able to give informed written consent in person.
             (i.e. patients who are capable of giving informed written consent on their own)

          -  Sex: Either sex. Women of child-bearing potential will be eligible for inclusion in
             this study. However they have to have a negative pregnancy test at the screening visit
             and will have to agree to further pregnancy testing at the time points determined in
             study assessments and procedures and practice one of the methods of contraception
             mentioned in the protocol from the screening visit until the end of the follow-up
             examination - Outpatient status

          -  corrected QT (QTc) <450 millisecond (msec) or <480msec for subjects with Bundle Branch
             Block. The QTc should be based on single or averaged QTc values of triplicate
             electrocardiograms (ECGs) obtained over a brief recording period.

          -  Liver function tests: Patients with aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) < 2x upper limit of normal (ULN); and Alkaline Phosphatase and
             bilirubin =< 1.5xULN (isolated bilirubin > 1.5ULN is acceptable if bilirubin is
             fractionated and direct bilirubin < 35%) at the screening visit.

        Randomization Criteria

          -  Patients whose UPDRS Part III total (on) scores is 10 points or more at week 0

          -  Patients who did not achieve an optimal therapeutic response by treatment with
             16mg/day Ropinirole CR and required higher dose of Ropinirole CR

          -  Patients who are 80% or more compliant taking study drug

        Exclusion Criteria

          -  Late stage advanced patients demonstrating incapacitating peak dose or biphasic
             dyskinsia on their stable dose of L-dopa.

          -  Patients who have used any other dopamine agonist (except for Ropinirole IR and CR)
             within 4 weeks prior to the screening phase.

          -  Patients who have been treated with the following drugs at 4 weeks or earlier before
             the start of the screening phase, and whose treatment regimen of the drug has been
             changed. Anticholinergic agents: trihexyphenidyl hydrochloride, piroheptine
             hydrochloride, mazaticol hydrochloride, metixene hydrochloride, biperiden
             hydrochloride, profenamine, amantadine hydrochloride,droxidopa, citicoline, selegiline
             hydrochloride, entacapone, zonisamide, Estrogens, CYP1A2 inhibitors.

          -  Patients who have been changing in smoking habit (started or stopped smoking) within
             the screening phase.

          -  Patients who have been treated with any other investigational drug within 12 weeks
             prior to the screening phase.

          -  Patients who present serious physical signs and symptoms other than those of the PD
             (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder).

          -  Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).

          -  Patients with a current or history of drug abuse or alcoholism.

          -  Patients with severe dementia such as score 3 or 4 of the UPDRS item 1 (Mentation,
             behaviour, and mood).

          -  Patients with current or history of major psychosis (e.g. schizophrenia or psychotic
             depression) such as score 3 or 4 of the UPDRS item 2 (thought disorder) or item
             3(depression).

          -  Patients who have received surgical treatment for PD in the past (e.g. pallidectomy,
             deep brain stimulation).

          -  Female patients who are pregnant or lactating, who may be pregnant, or who plan for
             pregnancy during the study or within 30 days after the last dose of the study drug.

          -  Unstable liver disease (as defined by the presence of ascites, encephalopathy,
             coagulapathy, hypoalbuminaemia, oesophageal or gastric varices or persistent
             jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's
             syndrome or asymptomatic gallstones). Chronic hepatitis B administered
             immunosuppressive agents due to risk of hapatitis B reactivation.

          -  Patients with a history of drug allergy to Ropinirole hydrochloride.

          -  Except for patients with a history of basal cell carcinoma, patients with a current or
             history of cancer or malignant tumor within 5 years prior to the screening phase.

          -  Others whom the investigator (subinvestigator) considers ineligible for the study.