E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive Supranuclear Palsy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036813 |
E.1.2 | Term | Progressive supranuclear palsy |
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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 assess the efficacy of Rasagiline using the PSP rating scale (PSPRS), aiming at a 33 % reduction of the reported deterioration (Golbe et al., 2007), i.e. a mean yearly increase of 6.5 instead of 9.7. To assess the need for additional L-DOPA therapy or the need to in-crease the dose of L-DOPA during the trial. |
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E.2.2 | Secondary objectives of the trial |
Reduction of gait disturbances and postural stability (as documented with posturographic measurement) Clinical safety and tolerability will be assessed by findings of physical and neurological examination, laboratory variables, adverse events in-cidence, vital signs, ECG, assessment of survival time Number of Subjects (%) who discontinue the study Number of Subjects (%) who discontinue the study due to AEs Assessment of survival time Additional endpoints: Secondary efficacy variables also will include inci-dence of dysphagia, gastrostomia, depression and pneumonia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all inclusion criteria to be eligible: 1.Clinical signs of PSP. Diagnosis will be made for patients with clini-cal probable PSP (Litvan et al., 1996). Patients will be included with PSP stage </= II (Golbe et al., 1997), at least with a PSPRS < 40 (Golbe et al., 2007) and according to the diagnostic criteria resumed after the NNIPPS trial (Bensimon et al., 2009) 2.Patients, male or female, aged 50 to 80 years 3.Subjects whose clinical condition at the time of enrolment does not or requires a low [< / = 500 mg /day] stable dose of L-DOPA for at least 2 weeks prior to study entry 4.Capability and willingness to give written signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
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E.4 | Principal exclusion criteria |
1. No clinically probable PSP 2. No written informed consent possible 3. Age > 80 or < 50 years 4. Dementia (MMSE 24) 5. Subjects with clinically significant psychiatric illness, including major depression 6. Subjects who have taken any experimental drugs within 60 days prior to baseline 7. Subjects who have used sympathomimetics (including over-the-counter remedies – nasal or oral), dextromethorphan, pethidine or St. John’s wort within 7 days prior to baseline. 8. Loss of postural reflexes (no independent walking possible, inability to stand unassisted, wheelchair-bound) 9. Feeding tube / recommendation for a feeding tube 10. Unintelligible speech 11. History of brain disease (e.g. repeated strokes, cerebral tumour, hydrocephalus) 12. MPTP exposure 13. Oculogyric crisis 14. Early severe autonomic failure 15. Systemic disorder affecting the brain 16. Women who are not postmenopausal (e.g. one year without men-strual periods) or surgically sterilized. 17. Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure 18. Subjects who have used antidepressants, including selective sero-tonin re-uptake inhibitors, tricyclic and tetracyclic antidepressants (except amitriptyline <= 50 mg/day, trazodone < = 100 mg/day, ci-talopram < = 20 mg/ day, sertaline < = 100 mg/day and paroxetine < = 30 mg/day, escitalopram < = 10 mg/day) within 42 days prior to baseline 19. Subjects who have used any drugs known to have been involved in a drug interaction via inhibition of hepatic CYP 1A2 within 30 days prior to baseline (cimetidine, ciprofloxacin, clarithromycin, enoxacin, erythromycin, fluvoxamine, isoniazide, nalidixic acid, norfloxacin, troleandomycin, zileuton) 20. Subjects who have used MAO inhibitors including reserpine and methyldopa within three months prior to baseline 21. Anti-emetic or antipsychotic medication with central dopamine an-tagonist activity (except quetiapine fumarate) within six months prior to baseline 22. Participation in a clinical trial within the last 30 days prior to study start 23. Unstable antiparkinsonian medication within 30 days before base-line 24. Previous use of Rasagiline or Selegiline 25. Subjects who have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study par-ticipation (based on the investigator’s judgment). Such conditions might include cardiovascular, vascular diseases, pulmonary, he-patic impairment (Child-Pugh score > 5), renal, or metabolic diseases or malignancies as determined by medical history, physical examination, laboratory tests, or ECG
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be the integral of the PSPRS changes from baseline over time measured during visits at 3, 6, 9, 12 months
The need for additional L-DOPA therapy or the need to increase the dose of L-DOPA during the trial |
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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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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End of study is the final examination of the last patient. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |