Depression MedDRA version: 20.0 Level: PT Classification code 10012378 Term: Depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: MAP4343
Pharmaceutical Form: Capsule
INN or Proposed INN: 3ß-methoxy pregn-5-en-20-one
CAS Number: 511-26-2
Current Sponsor code: MAP4343
Other descriptive name: 3ß-methoxy pregnenolon
Sponsors
MAPREG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Antidepressant drug Resistance level from to 2 to 4 inclusive; 2- Patient experiencing a Major Depressive Episod (MDE) according to DSM-V criteria. MDE can be isolated or recurrent. The diagnosis is based on Mini-International Neuropsychiatric Interview (MINI) test; 3- Patient should have received a previous antidepressant treatment in monotherapy: IRSS, IRSNA, Tricyclique, IMAO or other drug class prescribed at the maximal dose recommended before the selection; 4- Hamilton Depression Rating Scale (HDRS) scores > 21; 5- Global clinical Impressions scale (GCI) > 4; 6- Male or female patient, aged 18 to 65 years inclusive; 7- 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 (amenorrhoea duration at least 12 months); 8- Negative pregnancy test at screening baseline; 9- Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive; 10- 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; 11- Normal ECG recording on a 12-lead ECG at the screening visit: o 120 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1- MDE with mood congruent or not congruent psychotic characteristics; 2- 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); 3- suicidal risk in the last month before randomization (MINI 5.00; suicidal risk section or item 3 of HDRS=3); 4- 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 associated with bipolar disorder 1 or 2, schizophrenic or schizo-affective disorder should not be included; 5- Presence or history of protein drug hypersensitivity, or allergic disease diagnosed and treated by a physician; 6- Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation; 7- Any drug intake during the last month prior to the first administration except those defined in Section 5.3; 8- General anaesthesia within 3 months before administration; 9- Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months; 10- Positive HBs antigen or anti HCV antibody, or positive results for HIV 1 or 2 tests; 11- Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant, calculated creatinine clearance = 60 mL/min; 12- Blood donation (including in the frame of a clinical trial) within 2 months before administration; 13- 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; 14- 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); 15- Exclusion period of a previous study; 16- No possibility of contact in case of emergency 17- History or presence of drug or alcohol abuse (alcohol consumption > 40 grams / day); 18- Administrative or legal supervision;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy at 6 weeks on Hamilton scale of daily administration of MAP4343 with anti-depressing drug in add-on in patients with drug resistant depression (resistance level from 2 to 4 according to Thase & Rush classification, 1997).;Secondary Objective: - To determine the percentage of treatment responders patients (corresponding to a 50% decrease on Hamilton score) over the 6 weeks of treatment. - To determine the percentage of patients in remission (corresponding to a Hamilton score < 7) over the 6 weeks of treatment. - To evaluate the efficacy of MAP4343 from D1 to D43. - To evaluate the safety of MAP4343 in patients in add-on conditions. - To determine some pharmacodynamics parameters on brain morphology (structural MRI), brain response (functional MRI) and biomarkers (plasmatic quantification;Primary end point(s): HDRS score evolution between baseline and D43.;Timepoint(s) of evaluation of this end point: baseline and D43 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy: psychopathological evaluations at each study visit: HDRS, MADRS, BAS, CGI, QIDS-SR and GAF (only at D1 and D43). - Pharmacokinetic assessment: Cmax, tmax, AUCt, Kel, t1/2, AUCinf, %AUCextra, Vd/F, Cl/F, R for MAP4343 in plasma at each study visit from D1 to D43. - Safety parameters: AE, vital signs, 12-lead ECG, laboratory exams, physical exams. - Biomarkers evaluation by MRI at baseline and D43: o Hippocampal volume o Self-referential memory task o Sensitivity to reward and punishment o Cognitive tasks outside the MRI scanner MRI will be performed only in La Pitié Salpétrière hospital, Sainte-Anne and Michel Fontan - Plasmatic quantification of pregnenolone, CRPs, Interleukins 1, 6 and 10; ELK-1, BDNF and VEGF, tubulin isoforms acet and tyr;Timepoint(s) of evaluation of this end point: Efficacy: D1 and D43 PK: D1, D8, D15, D22, D29, D36, D43 Safety: during all the study MRI: Baseline and D43 Plasmatic biomarkers: Baseline and D43 | — |
Countries
France
Contacts
Public ContactYves DONAZZOLO
EUROFINS OPTIMED
Outcome results
None listed