| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic Parkinson's Disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| 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 |
The objectives of this trial are to evaluate the efficacy and safety of a dose range of
safinamide 50-100 mg p.o. q.a.m., compared to placebo as add-on therapy in subjects with idiopathic Parkinson’s Disease with motor fluctuations, who are receiving a stable dose of levodopa.
Evaluate the change from baseline to W24 in daily “on” time (“on” time without dyskinesia plus “on” time with minor dyskinesia) of a dose range of safinamide 50-100 mg p.o. q.a.m., compared to placebo as add-on therapy in subjects with idiopathic Parkinson’s Disease with motor fluctuations, who are receiving a stable dose of levodopa. |
|
| E.2.2 | Secondary objectives of the trial |
Evaluate the changes from baseline to W24 in a series of secondary clinical endpoints of a dose range of safinamide 50-100 mg p.o. q.a.m. compared to placebo as add-on therapy in subjects with idiopathic Parkinson’s Disease with motor fluctuations, who are currently receiving a stable dose of levodopa. These secondary endpoints will address changes in:
- Activities of daily living assessed using the UPDRS Section II during the “on” phase
- Cognition assessed using the specific Cogtest® battery
- Dyskinesias assessed using the Dyskinesias Rating Scale during the “on” phase
- The clinical status and severity assessed as a change in CGI
- Motor symptoms assessed using the UPDRS Section III during the “on” phase
- “Off” time assessed using the diary cards
- Percent change in levopoda dose
- Health Related Quality of life assessed using EQ5D and PDQ-39
- The clinical status assessed as Patient´s Global Impression of Change (PIGC)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of idiopathic Parkinson’s Disease of more than 3 years duration, with a Hoehn and Yahr stage of I-IV during an “off” phase. 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 6.4.9 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. Be levodopa responsive and have been receiving treatment with a stable dose of levodopa [3-10 doses per day of any levodopa preparation (including CR, IR or a combination of CR/IR), plus benserazide/carbidopa; with or without addition of a COMT inhibitor] and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the screening visit.
5. Have motor fluctuations, with >1.5 hours “off” time during the day (excluding morning akinesia).
6. Be able to maintain an accurate and complete diary (18-hour), with the help of a caregiver, recording “on” time, “on” time with minor dyskinesia, “on” time with troublesome dyskinesia, “off” time, and time asleep.
7. Willing and able to participate in the trial and has provided written, informed consent. |
|
| 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. Be in a late stage of Parkinson’s Disease, and experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms.
4. Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.
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 atrio-ventricular 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 a significant ECG abnormality, including QTc U 450 msec (males) or U 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 a score greater than or equal to 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 < 22, or a score greater than or equal to 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, levodopa, or other 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. Stereotactic surgery as a treatment for his/her Parkinson’s Disease.
18. Participation in a clinical trial within 30 days of entry into the trial (screening visit) or having received treatment with any investigational compound within 30 days or 5 halflives, whichever is longer, prior to screening.
19. Treatment with any agent known to significantly inhibit or induce drug-metabolising enzymes (e.g., barbiturates, phenothiazines, etc.) within 4 weeks preceding the screening visit.
20. Treatment with opioids (e.g., tramadol, meperidine derivatives), SNRI’s (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 positive test 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 a diagnostic laboratory test.
25. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
26. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Daily “on” time (“on” time without dyskinesia plus “on” time with minor dyskinesia), as measured by diary cards, change from baseline to W24 |
|
| 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 | Yes |
| 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 | 22 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| 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 |
|
| 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
|
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 | 25 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 25 |
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