Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: ropinirole PR/XR; ropinirole IR
Intervention description: Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.
The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).
Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.
Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.
Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.; Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.
The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).
Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.
Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.
Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.
Intervention MeSH terms: Ropinirole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 302.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy

Summary:

      To investigate the efficacy and the safety of ropinirole PR/XR tablets to ropinirole
      immediate release (IR) tablets with advanced Parkinson's disease in conjunction with L-dopa
      in a double-blind, parallel group comparison study.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion criteria at the start of the screening

          -  Patients who are diagnosed with advanced Parkinson's disease (PD) with severity of the
             modified Hoehn & Yahr criteria Stages II-IV.

          -  Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening
             phase and demonstrating lack of control with L-dopa therapy in the following
             circumstances. Wearing-off phenomena. On-off fluctuations. Delayed-on/No on phenomena.
             Not adequately controlled on L-dopa

          -  QTc<450 millisecond (msec) or <480msec for patients with Bundle Branch Block - values
             based on either single ECG values or triplicate electrocardiogram (ECG) averaged QTc
             values obtained over a brief recording period.

          -  Age:20 years 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 one's own)

          -  Sex: either sex. Female 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, agree to further pregnancy testing at the time points determined in study
             assessments and procedures and practice one of the following methods of contraception
             from the screening visit until the end of the follow-up examination. Abstinence.
             Injectable progestogen. Implants of levonorgestrel. Estrogenic vaginal ring.
             Percutaneous contraceptive patches. Intrauterine device (IUD) or intrauterine system
             (IUS) that meets the SOP effectiveness criteria as stated in the product label. Male
             partner sterilization (vasectomy with documentation of azoospermia) prior to the
             female subject's entry into the study, and this male is the sole partner for that
             subject. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault
             caps) plus spermicidal agent (foam /gel / film / cream / suppository)

          -  Both inpatient and outpatient status.

        Inclusion Criteria at the start of the non-inferiority verification phase

        -Patients whose Unified Parkinson's Disease Rating Scale (UPDRS) PartIII total (on) scores
        is 10 points or more at week 0.

        Exclusion Criteria:

          -  Late stage advanced subjects demonstrating incapacitating peak dose or biphasic
             dyskinesia on their stable dose of L-dopa.

          -  Patients who present serious physical signs and symptoms other than those of the PD
             (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The severity refers
             to Grade 3 according to "the Classification of the Severity of Adverse Experiences
             (Pharmaceutical affairs bureau/Safety division (PAB/SD) Notification No. 80, dated 29
             June 1992).

          -  Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).

          -  Patients with a current or history of drug abuse or alcoholism.

          -  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.

          -  Patients with chronic hepatitis typeB and/or type C which is positive of hepatitis B
             surface antigen (HBsAg) and/or hepatitis C antibody.

          -  Patients with a history of drug allergy to ropinirole hydrochloride (HCl).

          -  Patients with a current or history of cancer or malignant tumor.

          -  Others whom the investigator (subinvestigator) considers ineligible for the study.

        Exclusion criteria at the start of the non-inferiority verification phase

          -  Patients with severe dementia (e.g. score 3 or 4 of the UPDRS item 1 (Intellectual
             Impairment))

          -  Patients with current or history of major psychosis (e.g. schizophrenia or psychotic
             depression) core 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression).

          -  Patients who have used any dopamine agonist within 4 weeks prior to the
             non-inferiority verification phase

          -  Patients who have been treated with the following drugs at 4 weeks or earlier before
             the start of the non-inferiority verification phase, and whose treatment regimen of
             the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride (e.g.
             Artane®), piroheptine hydrochloride (Trimol®), mazaticol hydrochloride (Pentona®),
             metixene hydrochloride (Cholinfall®), biperiden hydrochloride (Akineton®), profenamine
             (Parkin®), amantadine hydrochloride (e.g. Symmetrel®),droxidopa (Dops®), citicoline
             (e.g. Nicholin®), selegiline hydrochloride (FP®), entacapone, (comutan®) zonisamide,
             Estrogens: e.g. estriol (e.g. Estriel®), CYP1A2 inhibitors: Ciprofloxacin HCl (e.g.
             Ciproxan®, enoxacin and fluvoxamine).

          -  Patients who have been treated with any other investigational drug within 12 weeks
             prior to the treatment phase.