E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013113 |
E.1.2 | Term | Disease Parkinson's |
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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 compare the efficacy of one dose strength (4 mg) of E2007 with that of placebo on motor function in patients with Parkinson's disease (PD) who are on optimised and stabilised therapy and experience end-of-dose “wearing off” motor fluctuations. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that the efficacy of entacapone on motor function in patients with PD who are on optimised and stabilised therapy and experience end-of-dose “wearing off” motor fluctuations, is consistent with what has been reported in other clinical trials.
To compare the safety and tolerability of E2007 to that of placebo.
Other: To assess the efficacy of E2007 on levodopa induced dyskinesias as measured by the Unified Parkinson’s Disease Rating Score (UPDRS) part IV dyskinesia items and the patient diary. To compare the effects of E2007 to that of placebo on levodopa use. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients with idiopathic PD fulfilling the (United Kingdom [UK]) Parkinson’s disease Society Brain Bank diagnostic criteria, with a good response to levodopa. 2. Patients must have been diagnosed with idiopathic PD at ≥ 30 years of age. In addition the onset of symptoms associated with Parkinson’s disease must have occurred ≥ 30 years of age. 3. Patients must have predictable motor fluctuations of the wearing OFF type with the presence of at least 2 hrs of OFF time during the waking day (excluding the morning OFF time) as evidenced by diary cards completed at screening and confirmed by diary data collected in the 3-day diaries completed before randomisation. 4. Before patients are randomised, they must be able to show that they are able to accurately complete the diary cards. During the diary-training period at Screening Visit 1, there must be diary evidence of at least one transition of OFF to ON or from ON to OFF. 5. Patients must rate between II-IV on the Hoehn &Yahr scale when in an OFF state. 6. Patients must be taking optimised levodopa (plus dopamine decarboxylase inhibitors [DDI]) therapy (according to the Investigator’s opinion) at least 3 times during the waking day (not including bedtime/night time dose) up to a maximum of 8 doses daily (including bedtime/night time dose). 7. Patients who are treated with DA or MAOB inhibitors or other anti-PD drugs must be on optimised and stable doses for at least 4 weeks prior to the Screening visit and must remain stable throughout the study. (revised per Amendment 02) Only levodopa dosage can be adjusted downwards in the first 6 weeks of the double-blind treatment phase. 8. In the Investigator’s opinion, patients must be able to distinguish their own motor states and the absence or presence of troublesome or non-troublesome dyskinesias. 9. In the Investigator’s opinion, patients are able to complete the study including the completion of the home diary cards and are capable of giving full written informed consent. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating women. 2. Women of child-bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g. abstinence, intrauterine device or barrier method plus hormonal method). These patients must have a negative serum β-human chorionic gonadotrophin (β-HCG) test at the initial screening visit (Visit 1) and a negative urine pregnancy test at the baseline visit (Visit 3). These patients must also be willing to remain on their current form of contraception for the duration of the study. Postmenopausal women may be recruited but must be amenorrhoeic for at least 1 year to be considered of non-child-bearing potential as determined by the Investigator. 3. Patients with a past or present history of drug or alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSM IV) criteria. 4. Patients with a past (within 1 year) or present history of psychotic symptoms requiring anti-psychotic treatment. Patients may be taking anti-depressant medication; however, the dose must be stable for 4 weeks prior to the Screening visit. Use of anti-psychotic medication including clozapine and quetiapine is prohibited. 5. Patients with a past (within 1 year) or present history of major depression, suicidal ideation or suicide attempts. 6. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastro-intestinal, haematological, endocrine or metabolic systems that might complicate assessment of the tolerability of the study medication. 7. Patients who have a past or present history of liver impairment, neuroleptic malignant syndrome, non-traumatic rhabdomyolysis or pheochromocytoma. 8. Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit). 9. Patients with current or prior treatment (within 4 weeks prior to the Screening visit) with medication known to induce the enzyme CYP3A4 (refer to Section 9.8.2 for list of prohibited medications). 10. Current or prior treatment (within 4 weeks prior to the Screening visit) with pergolide (only applies to patients entering after April 5, 2007), cabergoline (effective as of the date of the IRB/IEC approval of this amendment), tolcapone, methyldopa, budipine, reserpine, quetiapine or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine. (revised per Amendment 02) 11. Current treatment with non selective MAOA/B or combination of selective MAOA and selective MAOB inhibitors. 12. Patients with a known hypersensitivity to the active substance or to any of the excipients of entacapone. 13. Patients with previous stereotactic surgery (e.g. pallidotomy) for PD or with planned stereotactic surgery during the study period. 14. Patients receiving or with planned (next 6 months) deep brain stimulation. 15. Patients who have received entacapone previously or are currently using entacapone. 16. Patients who have received an investigational product within 4 weeks prior to the Screening visit or patients who have participated in a previous study with E2007. (revised per Amendment 02) 17. Patients with clinically significant cognitive impairment (Mini-Mental State Examination [MMSE] <24 or fulfilling DSM IV criteria for dementia due to PD). 18. Patients with conditions affecting the peripheral or central sensory system unless related to PD (such as mild sensory or pain syndromes limited to OFF periods) that could interfere with the evaluation of any such symptoms caused by the study drug. 19. Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the efficacy of one dose strength (4 mg) of E2007 with that of placebo on motor function in patients with PD who are on optimised and stabilised therapy and experience end-of-dose “wearing off” motor fluctuations.
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 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) | Yes |
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.8.4.1 | 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 | 40 |
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 | 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
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The end of the study will be date of the last visit of the last patient(s) participating in the trial as recorded in the CRF page end of study/earl withdrawal. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |