| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early stage Parkinson's Disease. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early stage Parkinson's Disease. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To characterize the dose response of fixed doses of ropinirole PR as monotherapy in patients with early stage Parkinson’s disease. |
|
| E.2.2 | Secondary objectives of the trial |
| To investigate the tolerability of fixed doses of ropinirole PR as monotherapy in patients with early stage Parkinson’s disease. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Diagnosis of idiopathic Parkinson’s disease (according to modified Hoehn & Yahr criteria Stages I-III.)
2. 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.
3. A baseline UPDRS motor score of at least 10.
4. 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.
5. Provide written informed consent for this study.
6. Be willing and able to comply with study procedures.
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the Investigator Brochure and product label.
Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subjects with Parkinson’s disease in whom dopaminergic therapy is not warranted at the time of enrolment (screening).
2. 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]).
3. Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
4. 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].
5. Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
6. Subjects with severe dizziness or fainting due to postural hypotension on standing.
7. Subjects with a personal history of melanoma.
8. 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.
9. 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 prior to enrolling (screening) in the study.
10. 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.
11. Current alcohol or drug dependence.
12. 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.
13. 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).
14. Subjects already 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 their normal smoking habit.
15. Women who are pregnant or breast-feeding.
16. Use of an investigational drug from 30 days or 5 half-lives (which ever is longer) prior to baseline (randomization) through to the end of the treatment period.
Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in UPDRS motor score at Week 4 of the Maintenance period. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Week 4 of the Maintenance period. |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include:
• Percentage of patients with a ≥ 5 point reduction from baseline in UPDRS motor score at Week 4 of the Maintenance Period.
• Percentage of patients with a ≥ 10 point reduction from baseline in UPDRS motor score at Week 4 of the Maintenance Period.
• Percentage of patients with a ≥ 10 point reduction from baseline in the UPDRS parts II and III combined at Week 4 of the Maintenance Period.
• Responder defined as patients with a ≥30% reduction in baseline UPDRS motor score at Week 4 of the Maintenance Period
• Change from baseline in the UPDRS parts II and III combined at Week 4 of the Maintenance Period
• Change from baseline in UPDRS Activities of Daily Living at Week 4 of the Maintenance Period
• Change from baseline in the total UPDRS score (parts I-III) at Week 4 of the Maintenance Period
• Change from baseline in the UPDRS part I (mentation) at week 4 of the Maintenance Period
• Responder defined as patients with a score of much improved or very much improved on the Clinical Global Impression – Global Improvement (CGI-I) scale at Week 4 of the Maintenance Period
• Percentage of subjects withdrawn from the study due to lack of efficacy. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| All endpoints will be evaluated at week 4 of the Maintenance period with the exception of the percentage of subjects withdrawn from the study due to lack of efficacy. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Alternative dose of the same IMP. |
|
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Estonia |
| Korea, Republic of |
| Russian Federation |
| Slovakia |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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