RESIST : Administration of MAP4343 in Antidepressant Non-Responders Patients Experiencing a Major Depressive Episode
Double-blind,Controlled,Randomized Phase 2 Study of Efficacy,Safety,Pharmacokinetics& Pharmacodynamics of Daily Oral Administration of MAP4343 During 6 Weeks in Antidepressant Non-responders Patients Experiencing a Major Depressive Episode
The study is a phase II, double-blind, randomized, placebo controlled, parallel, multicentric study in 110 patients with drug resistant depression.
This is a phase II, versus placebo, multicentre, double blind, randomized, parallel study in male or female patients with drug resistant depression.
This study targets the antidepressant non-responders' patients who have already experienced at least 2 antidepressant treatments with no success. It is estimated that about 2/3 of the patients treated with antidepressant drugs do not respond partially or completely to the actual conventional treatments (Selective Serotonin Reuptake Inhibitor and Serotonin and Norepinephrine Reuptake Inhibitor).
110 patients with drug resistant depression episode, aged 18 to 80 will be included in the study. They will be recruited from psychiatric consultations in the centers participating to the study.
Inclusion Criteria: TRD level from to 2 to 4 inclusive according to the Thase & Rush classification; Patient experiencing a Major Depressive Episode (MDE) according to DSM-5 criteria. MDE can be isolated or recurrent. The diagnosis is based on Mini-International Neuropsychiatric Interview (MINI) test; Patient who received a previous antidepressant treatment (AD-Y) in monotherapy with vortioxetine, duloxetine or venlafaxine) at optimized dosages during 6 weeks prior to randomization, associated or not to AD-potentiator (quetiapine), are eligible. Hamilton Depression Rating Scale (HDRS) score > 21; Clinical Global Impressions scale (CGI) > 4; Male or female patient, aged 18 to 80 years inclusive; Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, diaphragm or condoms) for the duration of the trial and for 4 months after the last study drug administration; Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months); Negative pregnancy test at screening baseline; Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive; Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests, urinalysis, hormonology). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator; Normal ECG recording on a 12-lead ECG at the screening visit: 120 < PR < 210 ms QRS < 120 ms QTcF ≤ 430 ms for male and < 450 ms for female, No sign of any trouble of sinusal automatism, Or considered NCs by investigators; Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position: 95 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg, 50 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg, 50 bpm ≤ HR ≤ 80 bpm, Or considered NCs by investigators; Signing a written informed consent prior to selection; Covered by Health Insurance System and/or in compliance with the recommendations of National Law in force relating to biomedical research. Exclusion Criteria: MDE with mood congruent or not congruent psychotic characteristics; Patient hospitalized following the procedures: Psychiatric care at the request of another person (soins psychiatriques à la demande d'un tiers) or Psychiatric care at the request of the state representative (soins psychiatriques sur décision du représentant de l'Etat); Suicidal risk in the last month before randomization (C-SSRS: answer yes to the item 3 and/or answer yes to section suicidal behavior; MINI 5.00; suicidal risk section or item 3 of HDRS ≥ 3); History of other psychiatric disorder than DME except global anxiety, social phobia, panic troubles that should be accepted. In particular, patients who experienced a depressive state in bipolar disorder 1 or 2, schizophrenic or schizoaffective disorder should not be included; Presence or history of drug hypersensitivity, or certain allergic-prone condition diagnosed that could represent a risk factor for an allergic shock; Presence or history of hypersensitivity to vortioxetine, duloxetine, venlafaxine or one of their excipients; Any history or presence of severe hepatic insufficiency and/or of hepatic disease which could lead to hepatic insufficiency; Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation; Any drug intake during the last month prior to the first administration except treatments for concomitant pathologies which are stable since at least 3 months; Benzodiazepine-type anxiolytics, hydroxyzine chlorhydrate, and add-on treatments are authorized within limits described in Section 5.3; For the previous drug intake, the investigator should consider the time needed to sufficiently eliminate a drug from body system, e.g. 5 half-lives of the drug; Subjects who received MAOI in monotherapy right before the selection (as ttX); General anesthesia within 3 months before administration; Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months; Positive HBs antigen or anti HCV antibody, or positive results for HIV 1 or 2 tests; Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant, calculated creatinine clearance ≤ 60 mL/min; Blood donation (including in the frame of a clinical trial) within 2 months before administration; Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development; Medical history which in the opinion of the investigator would make the patient unsuitable for participation in the study (including, but not limited, to patients with coronary insufficiency, thromboembolism diseases); Exclusion period of a previous study; No possibility of contact in case of emergency; History or presence of drug or alcohol abuse (alcohol consumption > 40 g/day); Administrative or legal supervision.