A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease
A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease
This is a double blind, fixed dose, parallel group study to characterize the dose response of
 ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson's
 disease. The primary endpoint of this study, mean change from baseline in total awake time
 spent "off' is the same endpoint as used in the ropinirole PR pivotal study for advanced
 Parkinson's disease patients. This study includes a wide range of ropinirole doses (4-24mg)
 with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7 hour difference in total
 awake time spent "off" compared with placebo. The dose of Ldopa will remain stable through
 the study, unless the subject experiences tolerability issues that require an L-dopa dose
 reduction. Up to three L-dopa dose reductions are allowed, making a total reduction of up to
 approximately 30%. Keeping the L-dopa dose constant where possible is important to avoid
 confounding the efficacy data. Clinical review of the primary and secondary endpoints will be
 performed in order to establish the lowest maximally effective therapeutic dose.
Inclusion Criteria:

 -  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 4 weeks prior to screening.

 -  A minimum of 3 hours awake "off-time" for each diary day recorded during the baseline
 period.

 -  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 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.

 -  Provide written informed consent for this study.

 -  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 diphasic
 dyskinesia on their stable dose of L-dopa

 -  Consumption of any dopamine agonist, including ropinirole, within four weeks of
 randomization in the study.

 -  Subjects with severe, clinically significant condition(s) other than Parkinson's
 disease which, in the opinion of the investigator, would 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
 which would preclude 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 who are 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.

 -  Subjects who have an active suicidal plan/intent or have had active suicidal thoughts
 in the past 6 months. Subjects who have 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 enrolment (randomization). Subjects already on chronic therapy with any
 of these agents may be enrolled but doses must have remained stable from 7 days prior
 to enrolment (randomization) through the end of the treatment period.

 -  Women who are pregnant or breast-feeding.

 -  Use of an investigational drug from 30 days or 5 half-lives (whichever is longer)
 prior to enrolment (randomization) through to the end of the treatment period. 15.
 Women who are pregnant or breast-feeding. 16. Use of an investigational drug from 30
 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through
 to the end of the treatment period.