Effect of 3-month treatment with F2695 (75mg OD) on improving functional recovery of patients with ischemic stroke. A Multicenter, Randomised, Double-blind, Parallel-group, Placebo-Controlled Study. LIFE-Study

Phase 3

Conditions: I69.3
Sequelae of cerebral infarction

Registration Number: DRKS00004394

Lead Sponsor: Pierre Fabre Médicament Represented by: Institut de Recherche Pierre Fabre

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 532

Inclusion Criteria

Male or female patient, 18 to 80 years of age, inclusively - Who had a confirmed acute ischemic stroke within the past 2 – 10 days , associated: with an unilateral motor deficit (hemiparesis or hemiplegia); with a National Institutes of Health stroke scale (NIHSS) motor score greater or equal to 5; with a modified Rankin Scale (mRS) of 4 or 5 - Able and willing to comply with the site rehabilitation program requirements - Signed written informed consent to take part in the study obtained from the patient. In case of impossibility for the patient to sign the consent form, the consent is to be witnessed by a third party completely independent from the investigator and the sponsor. This witness will have to sign the consent form and the patient will have to sign the consent form once his condition permits , before the end of the study. - Affiliated to a social security system, or is a beneficiary (if applicable in the national regulation). - Woman of childbearing potential must have been using an effective method of contraception (defined as surgical or hormonal birth control, or intra-uterine device only), assessed by the investigator, for at least 2 months before selection in the study, and must accept to go on using it during the whole duration of the study and up to 1 month after the last dose of the study treatment, in order to avoid pregnancy while being exposed to the study treatment.

Exclusion Criteria

Disease-related criteria: - Patient with motor sequelae from a previous stroke, - Patient with pre-existing or concomitant deficit that could interfere with clinical assessments, - Patient with aphasia preventing correct evaluation of motor and / or depression scales, - Patient with severe post-stroke condition (NIHSS score >20), - Patient with active depressive episode (MADRS score of more than 18 and / or a Clinical Global Impression scale in depression – CGIDepression > 3), - Patient with evidence of intra-cerebral haemorrhage on brain MRI or CT scan, - Patient needing carotid surgery within 3 months. Previous or concomitant treatment-related criteria: - Patient having taken within the month preceding inclusion one or more of the following drugs: o antidepressant drugs belonging to the classes of SSRIs, SNRIs and TCAs (whatever the indication), o monoamine oxidase inhibitors or any other drug which may increase the risk of serotonin syndrome (tramadol, triptans, propoxyphene, lithium…) except tamadol (or related opiod analgesics) and triptans drugs for which the wash-out is 72 hours before the first intake of the study treatment o neuroleptic drugs, except the antiemetic drugs for which the wash-out is 48 hours before the first intake of the study treatment, o alpha1-adrenoreceptor antagonists, except the intravenous antihyertensive drugs for which the wash-out is 24 hours before the first intake of the study treatment, o central nervous system stimulants (modafinil, methylphenidate, amphetamines…), - Patient with an history of intolerance or hypersensitivity to F2695, milnacipran or other SNRIs, SSRIs, or selective noradrenergic reuptake inhibitors, - Patient displaying criteria for psychoactive substance abuse or dependency (according to DSM-IV). Patient-related criteria: - Patient with severe cognitive impairment or dementia, - Patient presents an acute coronary syndrome, - Patient presenting cardiac rhythm disorder (including tachyarrhythmia) in the 3 months preceding the inclusion, - Patient presenting uncontrolled arterial hypertension or symptomatic postural hypotension, - Patient with history of myocardial infarction in the preceding 3 months, - Patient unable to safely swallow capsules, - Patient presenting disability (mRS > 1) prior to the current stroke (rheumatologic diseases, sequelaes of traumatic diseases or from previous stroke injury…), - Patient with the following abnormal clinical laboratory test results: o Liver function test values (aspartate aminotransferase and/or alanine aminotransferase) greater than 3 times the upper limit of normal, o An estimated glomerular filtration rate (eGFR) <60ml/min/1,73m2, - Patient with a history of coagulation or haemostasis disorders which the investigator deems incompatible with study implementation, - Patient with a history of narrow angle glaucoma, - Patients with a prior history of seizures/epilepsy (before the onset of stroke event), - Patient presenting with a severe acute or chronic disease which the investigator deems incompatible with study implementation. This includes evidence of malignancy or any significant or progressive disease (endocrine, respiratory, renal, hepatic, gastrointestinal, neurologic disease or infectious disease), - Patient liable not to comply with protocol instructions and/or with treatment (including rehabilitation therapy), in the investigator's opinion, - Male patients with history of obstructive voiding symptoms, including urinary retention, -

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of this study is to assess the effect of 3-month treatment with F2695 (75 mg OD) on improving functional recovery in patients with moderate to severe motor deficits after an ischemic stroke.<br><br>The primary parameter is the response rate, defined as the percentage of patients with a mRS score 1 in week 12

Secondary Outcome Measures

Name	Time	Method
- To assess the effect of F2695 on:<br>• Motor recovery,<br>• Occurrence and recurrence of depression,<br>- To evaluate the safety and tolerability of F2695 in patients with ischemic stroke.<br><br>The secondary parameter is the change in the following values ??at week 12 compared to baseline:<br>1) mRS score<br>2) moderate NIHSS total score and moderate NIHSS motor score<br>3) Percentage of patients with:<br>3.1) NIHSS score = 5 at week 12<br>3.2) At least one moderate to severe depressive episode (MADRS score> 25 and / or CGI depression score> 4) at week 12