E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment-Associated Dyskinesia in Parkinson's Disease |
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MedDRA Classification |
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 |
The primary objective of this study is to demonstrate efficacy of 1 mg Sarizotan HCl b.i.d. after 12 weeks and after 24 weeks (maintenance of efficacy) in the treatment of dyskinesia in Parkinson's disease. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to collect safety and tolerability data for 1mg Sarizotan HCl b.i.d. in Parkinson patients |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. The subject has given his/her written informed consent to participate in the study. 2. The subject is an out-patient aged 30 years or above. 3. (For female subjects of child-bearing potential) The subject is using a reliable method of contraception and must provide a negative pregnancy test at entry into the study. 4. The subject presents with a diagnosis of idiopathic Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria. 5. The subject presents with Stage 2.5 or above on the Hoehn and Yahr staging system. 6. The subject's dyskinesia is present during more than 25% of the waking day (historical information in agreement with the assessment of the investigator according to item 32 of UPDRS). 7. The subject's dyskinesia is at least moderately disabling (historical information in agreement with the assessment of the investigator according to item 33 of UPDRS). 8. The subject has at least 4 ticks/day “ON time with dyskinesia” on each of the two days the diary was completed before the inclusion visit (at visit 2). 9. The subject has participated successfully in a diary-card training session. 10. The subject has been on a stable dose of anti-Parkinsonian drugs except L-dopa for a period of at least 8 weeks up to the screening visit. 11. In the judgment of the investigator based on the subject’s history, previous treatments, and the investigator’s overall knowledge of PD, the subject is considered as being optimally treated at the present time (i.e., further adjustments of current medication will not further improve the subject's symptoms of Parkinson's disease). 12. The subject has at least 4 ticks/day “ON time with dyskinesia” on each of the two days the diary was completed before visit 3. 13. The subject shows adequate compliance with the instructions for filling in the diary. 14. The subject shows adequate compliance with the schedule for intake of study medication |
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E.4 | Principal exclusion criteria |
1. The subject has, within the four weeks up to inclusion, started treatment with any classical or atypical neuroleptics (including metoclopramide) and/or antidepressants and/or anxiolytics (including buspirone). 2. The subject's dosage with any of the medications listed in (1) above has changed within the four weeks up to inclusion. 3. Any commencement or change of dosage with any of the medications listed in (1) above during the study period is anticipated. 4. (For female subjects) The subject is pregnant or lactating. 5. The subject is participating in another clinical study or has done so within the past 30 days. 6. The subject has participated in the SPLENDID study (EMR 62 225-001) or the SPIRID-study (EMR 62 225-006). 7. The subject has received neurosurgical intervention related to PD (e.g. deep brain stimulation, thalamotomy etc.) or is scheduled to do so during the study period. 8. The subject has any clinically significant illness that, in the Investigator’s opinion, might interfere with the subject's ability to participate in the study. 9. The subject has relevant renal impairment as measured by Creatinine >2 × ULN. 10. The subject has relevant hepatic impairment as either measured by total bilirubin > 2 x ULN or has a history of moderate or severe hepatic insufficiency or has moderate or severe liver cirrhosis. 11 The subject is suffering from any dementia or other psychiatric illness that prevents him/her from giving informed consent. 12 The subject has legal incapacity or limited legal capacity. 13. The subject has a history of allergic asthma. [Note: This is to minimize the risk of severe allergic reactions to ACTH following the stimulation test.] |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary target variable is defined as a responder rate based on the sum score of items 32 and 33 of the UPDRS. A subject is defined as a responder if he/she improves at least 25% from baseline in the sum score of items 32 and 33. That score covers the duration of dyskinesia and the disability caused by dyskinesia. It reflects historical information from the subject but may be modified by the investigator on the basis of office examination. The assessment of items 32 and 33 is performed exclusively during the "best ON" phase. This is important since the retrospective assessment of dyskinesia can be biased by the actual condition of the subject. The UPDRS item 32 and 33 will be assessed first at the Screening Visit, since the inclusion criteria 6 and 7 depend on it. The assessment after the placebo run-in phase is defined as Baseline. This is to reduce the placebo effect. The endpoint 1 of the study will be after 12 weeks of doubleblind treatment and the endpoint 2 will be after another 12 weeks of treatment. The 3 major visits (Baseline, Endpoint 1, Endpoint 2) will follow an identical agenda in order to exclude influences of accompanying tasks and shifts of the time schedule on the assessment of the primary target variable.
Other efficacy variables: - UPDRS(partsItoVI) - Differences from baseline in variables derived from the subject's diary. - Modified Abnormal Involuntary Movement Scale, at rest and provoked - Patient's and clinical global impression - Daily dose of L-dopa Other variables: - Plasma concentrations of Sarizotan and its metabolites. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 17 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 17 |