| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic Parkinson's Disease |
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| E.1.1.1 | Medical condition in easily understood language |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| 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 |
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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 |
The objectives of this trial are to evaluate the safety and efficacy of two doses of safinamide (50 and 100 mg p.o. q.a.m.), compared to placebo, as add-on therapy in subjects with early idiopathic Parkinson’s Disease who are currently receiving a stable dose of a single dopamine agonist.
Evaluate the changes from baseline to W24 in motor symptoms (UPDRS Section III). |
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| E.2.2 | Secondary objectives of the trial |
| Evaluate the changes from baseline to W24 in activities of daily living, cognition, change in global clinical status, responder rates with regard to motor symptoms and health related quality of life |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of idiopathic Parkinson’s disease of less than 5 years duration, with a Hoehn and Yahr stage of I III. The diagnosis should be based on medical history and neurological examination.
2. Between the ages of 30 to 80 years, inclusive, at screening.
3. If female, be either post menopausal for at least 2 years, surgically sterilised or have undergone hysterectomy or, if of child bearing potential, be willing to avoid pregnancy by using an adequate method of contraception as defined in Section 6.4.10 for four weeks prior to, during and four weeks after the last dose of trial medication. For the purposes of this trial, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive.
4. Receiving treatment with a single dopamine agonist at a stable dose for at least 4 weeks prior to the screening visit.
5. Willing and able to participate in the trial and have provided written, informed consent.
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| E.4 | Principal exclusion criteria |
1. Any indication of forms of Parkinsonism, other than idiopathic Parkinson’s Disease.
2. If female, be pregnant or lactating.
3. Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.
4. Currently experiencing end of dose wearing off or on-off phenomena, disabling peak dose or biphasic dyskinesias, or unpredictable or widely swinging fluctuations.
5. Current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease, including acute gastric ulcer, hypertension that is not well controlled, asthma, chronic obstructive pulmonary disease (COPD), and Type I diabetes. (Subjects with a history of gastric ulcer who have not had a recent episode of acute gastritis and are not currently experiencing gastric pain will be eligible for inclusion).
6. Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months of the screening visit, or significant ECG abnormality, including QTc ≥ 450 msec (males) or ≥ 470 msec (females), where QTc is based on Bazett’s correction method.
7. Have received treatment with safinamide previously.
8. Concomitant disease likely to interfere with the trial medication (e.g. capable of altering absorption, metabolism or elimination of the trial drug).
9. History of, or current psychosis (e.g. schizophrenia or psychotic depression), or with a score ≥ 3 on item 2 (thought disorder) or 3 (depression) of the UPDRS Section I at screening.
10. Evidence of dementia or cognitive dysfunction, as indicated by a MMSE score < 24, or a score ≥ 3 on item 1 (mentation) of the UPDRS, Section I at screening.
11. Depression, as indicated by a GRID HAMD (17 item scale) score > 17 at screening.
12. History of allergic response to anticonvulsants or anti-Parkinsonian agents.
13. Mental or physical condition (e.g., neurotic behaviour, crippling degenerative arthritis, or limb amputation), which would preclude performing efficacy or safety assessments.
14. Hypersensitivity or contraindications to MAO B inhibitors.
15. Current history of severe dizziness or fainting on standing, due to postural hypotension.
16. Neoplastic disorder, which is either currently active or has been in remission for less than one year.
17. Participation in a clinical trial within 30 days of entry into the trial (screening visit) or has received treatment with any investigational compound within 30 days or 5 half lives, whichever is longer, prior to screening.
18. Treatment of their Parkinsonian symptoms with a medication, other than a stable dose of a single dopamine agonist, during the 8 weeks preceding the screening visit.
19. Treatment with any agent known to significantly inhibit or induce drug-metabolizing enyzmes (e.g., barbiturates, phenothiazines, etc.) within 4 weeks preceding the screening visit.
20. Treatment with opioids (e.g., tramadol, meperidine derivatives), SNRIs (e.g., venlafaxine, duloxetine), tri- or tetra-cyclic antidepressants, MAO inhibitors (e.g. selegiline), in the 8 weeks prior to the screening visit. Dextromethorphan will be permitted if used for treating cough.
21. Treatment with a depot neuroleptic within one injection cycle, or oral neuroleptics within 4 weeks prior to the screening visit.
22. Treatment with a drug that has hepatotoxic potential, e.g., tamoxifen, within 4 weeks, or received radiation therapy or a drug with cytotoxic potential, e.g, chemotherapy, within one year prior to the screening visit.
23. Diagnosis of HIV, or tests positive for Hepatitis C antibodies, or Hepatitis B surface antigen.
24. Any abnormality that the investigator deems to be clinically relevant, either on medical history, physical examination, ECG or in a diagnostic laboratory test.
25. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.
26. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| UPDRS Section III score change from baseline to W24 |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
-UPDRS Section II(ADL) score change from baseline to W24
Cogtest PD battery test score change from baseline to W24
CGI- Severity scale score change from baseline to W24
Proportion of subjects with scores 1,2,3 (showing improvement) on the CGI change scale at W24
CGI -Change scale at W24
Proportion of responders (subjects with at least 30% improvement on UPDRS - Section III score change from baseline to W24)
EQ5D score change from baseline to W24
PDQ-39 score change from baseline to W24
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | 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
| 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 | 32 |
| 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 | Yes |
| 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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For administrative and safety reporting purposes the end of the trial will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all trial sites.
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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 | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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