Resumen

Parkinson's disease is a major neurodegenerative disorder in which there is a progressive loss of nigrostriatal dopaminergic neurons. The understanding that PD is a syndrome of dopamine (DA) deficiency led to the introduction in the clinical practice of L-dopa, a precursor of DA that crosses the blood brain barrier, and also to the use of selective inhibitors of MAO B, the major DA metabolising enzyme in man. This is a double-blind, placebo-controlled, parallel-group, randomised, multi-centre, multi national, Phase III trial, comparing two doses of safinamide (50 and 100 mg p.o. q.a.m.) versus placebo as add-on therapy to a stable dose of a single dopamine agonist in subjects with early idiopathic Parkinson's Disease. The principal efficacy measure, i.e., change in mean value of UPDRS - Section III total score from baseline to endpoint, was chosen based on regulatory guidance and prior use in other trials in similar populations.

Elegibilidad

Edad mínima: 30 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

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.
to 80 years, inclusive, at screening.
If female, be either post menopausal for at least 2 years, surgically sterilised or have undergone hysterectomy or, if of child bearing potential they must be willing to avoid pregnancy by using an adequate method of contraception for four weeks prior to, during and four weeks after the last dose of study medication. For the purposes of this study, 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.
Receiving treatment with a single dopamine agonist at a stable dose for at least 4 weeks prior to the screening visit.
Willing and able to participate in the study and have provided written, informed consent.

Criterios de exclusión

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:
Any indication of forms of Parkinsonism, other than idiopathic Parkinson's Disease.
If female, be pregnant or lactating.
Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.
Currently experiencing end of dose wearing off or on-off phenomena, disabling peak dose or biphasic dyskinesias, or unpredictable or widely swinging fluctuations.
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.
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.
Have received treatment with safinamide previously.
Concomitant disease likely to interfere with the study medication (e.g. capable of altering absorption, metabolism or elimination of the study drug).
History of, or current psychosis (e.g. schizophrenia or psychotic depression) or a score ≥ 3 on item 2 (thought disorder) or 3 (depression) of the UPDRS, Section I at screening.
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.
Depression, as indicated by a GRID-HAMD (17-item scale) score \> 17 at screening.
History of allergic response to anticonvulsants or anti-Parkinsonian agents.
Mental or physical condition (e.g., neurotic behaviour, crippling degenerative arthritis, or limb amputation), which would preclude performing efficacy or safety assessments.
Hypersensitivity or contraindications to MAO B inhibitors.
Current history of severe dizziness or fainting on standing, due to postural hypotension.
Neoplastic disorder, which is either currently active or has been in remission for less than one year.
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.
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.
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.
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.
Treatment with a depot neuroleptic within one injection cycle, or oral neuroleptics within 4 weeks prior to the screening visit.
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.
Diagnosis of HIV, or tests positive for Hepatitis C antibodies, or Hepatitis B surface antigen.
Any abnormality that the investigator deems to be clinically relevant, either on medical history, physical examination, ECG or in a diagnostic laboratory test.
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.
Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

Intervenciones

drug

Safinamide (as add-on therapy)

Safinamide, (S)-(+)-2-\[4-(3-fluorobenzyloxy) benzylamino\] propanamide methanesulfonate, is an a-aminoamide derivative

drug

Safinamide (as add-on therapy)

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

drug

Safinamide (as add-on therapy)

Safinamide add-on therapy with subjects with IPD treated with single dopamine agonist

Ubicaciones

Hospital Español

Buenos Aires, Argentina

Instituto de Neurociencias Buenos Aires S.A.

Buenos Aires, Argentina

Clinica IMECO

Capital Federal, Argentina

Hospital Italiano de Buenos Aires

Capital Federal, Argentina

Instituto de Investigaciones Neurológicas Raul Carrea FLENI

Capital Federal, Argentina

Instituto Frenopatico S.A.

Capital Federal, Argentina

Instituto Medico Congreso

Ciudad Autonoma de Bs. As., Argentina

Instituto Argentino de Investigacion Neurologica SRL

Ciudad Autonoma de, Argentina

Instituto INEBA

Ciudad Autónoma de Bs. As., Argentina

Hospital Privado Centro Médico de Córdoba

Córdoba, Argentina

Hospital Universitario Austral

Pilar, Argentina

A Phase III, Double-blind, Placebo-controlled Randomised Trial to Determine the Efficacy and Safety of a Low (50 mg/Day) and High (100 mg/Day) Dose of Safinamide, as add-on Therapy, in Subjects With Early Idiopathic Parkinson's Disease Treated With a Stable Dose of a Single Dopamine Agonist

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Safinamide (as add-on therapy)

Safinamide (as add-on therapy)

Safinamide (as add-on therapy)

Ubicaciones

Hospital Español

Instituto de Neurociencias Buenos Aires S.A.

Clinica IMECO

Hospital Italiano de Buenos Aires

Instituto de Investigaciones Neurológicas Raul Carrea FLENI

Instituto Frenopatico S.A.

Instituto Medico Congreso

Instituto Argentino de Investigacion Neurologica SRL

Instituto INEBA

Hospital Privado Centro Médico de Córdoba

Hospital Universitario Austral

Patrocinadores