A Fixed Dose, Dose Response Study for Ropinirole Prolonged Release in Patients With Early Stage Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: ropinirole monotherapy; placebo monotherapy
Intervention description: ropinirole as monotherapy in Parkinson's disease; placebo as monotherapy in Parkinson's disease
Intervention MeSH terms: Ropinirole
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 186.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      This study is a fixed dose, dose response study to characterize the dose response for
      ropinirole PR in early stage PD patients (Hoehn & Yahr stages I-III). After screening and
      baseline assessments, subjects will be randomized to one of six final target treatment groups
      (placebo, 2, 4, 8, 12 or 24mg/day ropinirole PR). The study will consist of a screening
      period, an up-titration period, a maintenance period, a down titration period and a follow up
      period. This study utilizes change from baseline in the UPDRS motor score as the primary
      endpoint, in line with that used in the ropinirole PR monotherapy pivotal study
      (SK&F101468/168). Clinical review of the primary and secondary endpoints will be performed in
      order to establish the lowest maximally effective therapeutic dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn & Yahr
             criteria Stages I-III.)

          -  Subjects aged 30 years or greater at screening. Women of child-bearing potential must
             be practicing a clinically accepted method of contraception during the study and for
             at least one month prior to randomization and one month following completion of the
             study. Acceptable contraceptive methods include abstinence, oral contraception,
             injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring,
             percutaneous contraceptive patches, surgical sterilisation, male partner
             sterilization, intrauterine device [IUD], or double barrier method: condom or
             occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent
             (foam/gel/film/cream/suppository.

          -  A baseline UPDRS motor score of at least 10.

          -  Limited prior exposure to low or moderate doses of L-DOPA (up to 3 months in total) or
             dopamine agonists including ropinirole (up to 6 months in total) is allowed provided
             treatment is discontinued for a minimum of 4 weeks prior to screening.

          -  Provide written informed consent for this study.

          -  Be willing and able to comply with study procedures.

        Exclusion Criteria:

          -  Subjects with Parkinson's disease in whom dopaminergic therapy is not warranted at the
             time of screening.

          -  Subjects with severe, clinically significant condition(s) other than Parkinson's
             disease which, in the opinion of the investigator, render the subject unsuitable for
             the study (e.g., psychiatric, haematological, renal, hepatic, endocrinology,
             neurological [other than Parkinson's disease], cardiovascular, or active malignancy
             [other than basal cell carcinoma]).

          -  Subjects with crippling degenerative arthritis or other physical or mental conditions
             precluding accurate assessment of efficacy or safety.

          -  Subjects with prior or current major psychosis (e.g., schizophrenia or psychotic
             depression) e.g. scoring 3 or 4 on UPDRS item 2 [thought disorder] or item 3
             [depression].

          -  Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1
             [mentation].

          -  Subjects with severe dizziness or fainting due to postural hypotension on standing.

          -  Subjects with a personal history of melanoma.

          -  Subjects with clinically significant abnormalities in laboratory or ECG tests at
             Screening. If findings are outside the normal range and the subject is included, it
             must be documented by the investigator that the findings are not of clinical
             significance.

          -  Subjects diagnosed with an impulse control disorder. The modified MIDI will be
             conducted at screening. Subjects who score positive for this screen must be referred
             to a specialist for diagnostic evaluation prior to enrolling (screening) in the study.

          -  Subjects with an active suicidal plan/intent or have had active suicidal thoughts in
             the past 6 months. Subjects with a history of suicide attempt in the last 2 years or
             more than 1 lifetime suicide attempt.

          -  Current alcohol or drug dependence.

          -  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.

          -  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 baseline (randomization).

          -  Subjects on chronic therapy with any of these agents may be enrolled but doses must
             have remained stable from 7 days prior to baseline (randomization) through the end of
             the treatment period. Smokers should maintain normal smoking habit.

          -  Women who are pregnant or breast-feeding.

          -  Use of an investigational drug from 30 days or 5 half-lives (which ever is longer)
             prior to baseline (randomization) to the end of the treatment period.