| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Parkinson's disease. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced 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 | 16.0 |
| 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 characterise the dose response for ropinirole PR as adjunctive treatment to L-dopa in patients with advanced Parkinson's disease. |
|
| E.2.2 | Secondary objectives of the trial |
| To investigate the tolerability of fixed doses of ropinirole PR as adjunctive treatment to L-dopa in patients with advanced 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 II-IV) and demonstrating lack of control with L-dopa therapy (e.g. end of dose akinesia, simple on/off fluctuations).
2. Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening.
3. A minimum of 3 hours awake “off-time” for each diary day recorded during the baseline period.
4. 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.
5. Provide written informed consent for this study.
6. Be willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.
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. Late stage advanced subjects demonstrating incapacitating peak dose or diphasic dyskinesia on their stable dose of L-dopa
2. Consumption of any dopamine agonist, including ropinirole, within four weeks of randomization in the study.
3. 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]).
4. Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
5. 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].
6. Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
7. Subjects with severe dizziness or fainting due to postural hypotension on standing.
8. Subjects with a personal history of melanoma.
9. 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.
10. 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.
11. 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.
12. Current alcohol or drug dependence.
13. 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.
14. 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.
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.
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) |
The primary endpoint for the adjunctive study will be:
Change from baseline in total awake time spent “off” at Week 4 of the Maintenance Period
The general definition of “off-time” includes a lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. |
|
| 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 proposed secondary endpoints include:
• Responder rate, defined as the proportion of subjects with 20% reduction in baseline “off-time” at Week 4 of the Maintenance Period
• Percentage of subjects with a ≥1 hour reduction in baseline “off-time” at Week 4 of the Maintenance Period
• Percentage of subjects with a ≥2 hour reduction in baseline “off-time” at Week 4 of the Maintenance Period
• Responder rate, defined as the proportion of subjects 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
• Change from baseline in absolute awake time spent “on” without troublesome dyskinesia at Week 4 of the Maintenance Period
• Change from baseline in absolute awake time spent “on” at Week 4 of the Maintenance Period
• Change from baseline in UPDRS Motor score, with subjects in an “on” state, at Week 4 of the Maintenance Period.
• Change from baseline in UPDRS ADL score, with subjects in an “on” state at Week 4 of the Maintenance Period.
• Change from baseline in UPDRS ADL score, with subjects in an “off” state at Week 4 of the Maintenance Period.
• Change from baseline in UPDRS part I at Week 4 of the Maintenance Period.
• Change from baseline for Total Sleep Time during the night time hours of sleep, as recorded by subject diaries, at Week 4 of the Maintenance Period
• Subjects dropping out from study due to lack of efficacy.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| It is proposed that secondary endpoints will be evaluated at week 4 of the Maintenance Period with the exception of "Subjects dropping out from 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 medicinal product. |
|
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
| Argentina |
| Chile |
| Estonia |
| Korea, Republic of |
| Russian Federation |
| Slovakia |
| Taiwan |
| 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
|
| The end of trial is the last visit of the last subject undergoing the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| 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 |
Print
