A Fixed Dose Study of Ropinirole Prolonged Release as Adjunctive Treatment in Patients With Advanced Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: ropinirole/L-dopa; placebo/L-dopa
Intervention description: Ropinirole as adjunctive therapy with L-dopa; Placebo as adjunctive therapy with L-dopa
Intervention MeSH terms: Ropinirole; Levodopa; Dihydroxyphenylalanine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 352.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.