NCT03870776已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mapreg
- 入组人数
- 126
- 试验地点
- 10
- 主要终点
- Hamilton Depression Rating Scale score evolution between baseline and D43
研究概览
简要总结
The study is a phase II, double-blind, randomized, placebo controlled, parallel, multicentric study in 110 patients with drug resistant depression.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo group A
Placebo Comparator
Patients will receive the placebo during 42 days.
干预措施: Placebo (Drug)
MAP4343 group B
Experimental
Patients will receive daily dose 1 during 42 days.
干预措施: MAP4343 (Drug)
MAP4343 group C
Experimental
Patients will receive daily dose 2 during 42 days.
干预措施: MAP4343 (Drug)
结局指标
主要结局
Hamilton Depression Rating Scale score evolution between baseline and D43
时间窗: 43 days
Assessment of HDRS score with 17 items with sides 0 to 2 or 0 to 4. The scores from 0 to 4 correspond respectively to symptoms: absent, doubtful or insignificant, light, moderate, important, those ranging from 0 to 2 to symptoms: absent, doubtful or slight, overt or severe. The total score consists of the addition of the individual scores.
次要结局
- Efficacy of treatment assessed by psychopathological evaluations with Brief Anxiety Scale(43 days)
- Efficacy of treatment assessed by psychopathological evaluations with Hamilton Depression Rating Scale(43 days)
- Efficacy of treatment assessed by psychopathological evaluations with Montgomery and Asberg Depression rating Scale(43 days)
- Efficacy of treatment assessed by psychopathological evaluations with Scale of Global Clinical Impressions(43 days)
- Efficacy of treatment assessed by psychopathological evaluations with Quick Inventory of Depressive Symptoms(43 days)
- Efficacy of treatment assessed by psychopathological evaluations with General Assessment Functioning(43 days)
- Pharmacokinetic assessments with observed maximum plasma concentration (Cmax);(127 days)
- Pharmacokinetic assessments with first time to reach Cmax (tmax);(127 days)
- Pharmacokinetic assessments with elimination rate constant (Kel);(127 days)
- Pharmacokinetic assessments with plasma elimination half-life (t1/2);(127 days)
- Pharmacokinetic assessments with plasma area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase (AUCinf);(127 days)
- Pharmacokinetic assessments with percentage of extrapolated AUCinf (%AUCextra);(127 days)
- Pharmacokinetic assessments with volumn of distribution (Vd/F);(127 days)
- Pharmacokinetic assessments with Clearance (Cl/F);(127 days)
- Pharmacokinetic assessments with accumulation ratio (R);(127 days)
- Safety parameters assessed by the number of adverse events (AE)(127 days)
- Safety parameters assessed - Heart rate(127 days)
- Safety parameters assessed by blood pressure(127 days)
- Safety parameters assessed - 12-lead Electrocardiogramm(127 days)
- Safety parameters assessed - 12-lead ElectrocardiogrammPR;(127 days)
- Safety parameters assessed -12-lead Electrocardiogramm : QT(127 days)
- Safety parameters assessed - 12-lead Electrocardiogramm : QTc(127 days)
- Safety parameters assessed by hematology parameters : Haemoglobin(127 days)
- Safety parameters assessed by hematology parameters: Haematocrit(127 days)
- Safety parameters assessed by hematology parameters: Red blood cells(127 days)
- Safety parameters assessed by hematology parameters: White blood cells(127 days)
- Safety parameters assessed by hematology parameters:Neutrophils(127 days)
- Safety parameters assessed by hematology parameters: Eosinophils(127 days)
- Safety parameters assessed by hematology parameters: Basophils(127 days)
- Safety parameters assessed by hematology parameters: Lymphocytes(127 days)
- Safety parameters assessed by hematology parameters: Monocytes(127 days)
- Safety parameters assessed by hematology parameters: Platelets(127 days)
- Safety parameters assessed by hematology parameters: Reticulocytes;(127 days)
- Safety parameters assessed by red blood cells indices(127 days)
- Safety parameters assessed by hemostasis parameters(127 days)
- Safety parameters assessed by biochemistry parameters: Chlore(127 days)
- Safety parameters assessed by serology parameters(127 days)
- Safety parameters assessed by biochemistry parameters : Glucose(127 days)
- Safety parameters assessed by biochemistry parameters: Creatinine(127 days)
- Safety parameters assessed by biochemistry parameters: SGOT/ASAT(127 days)
- Safety parameters assessed by biochemistry parameters: SGOT/ALAT(127 days)
- Safety parameters assessed by biochemistry parameters:GGT(127 days)
- Safety parameters assessed by biochemistry parameters: Alkalin phosphatase(127 days)
- Safety parameters assessed by biochemistry parameters: CPK(127 days)
- Safety parameters assessed by biochemistry parameters: Total bilirubin(127 days)
- Safety parameters assessed by biochemistry parameters: Conjugated bilirubin(127 days)
- Safety parameters assessed by biochemistry parameters: Uric Acid(127 days)
- Safety parameters assessed by biochemistry parameters: Cholesterol(127 days)
- Safety parameters assessed by biochemistry parameters: Triglycerides(127 days)
- Safety parameters assessed by biochemistry parameters: Sodium(127 days)
- Safety parameters assessed by biochemistry parameters: Potassium(127 days)
- Safety parameters assessed by biochemistry parameters:Calcium(127 days)
- Safety parameters assessed by biochemistry parameters:Total protein(127 days)
- Safety parameters assessed by biochemistry parameters:Albumin(127 days)
- Safety parameters assessed by hormonology parameters(127 days)
- Safety parameters assessed by weight measurement(127 days)
- Safety parameters assessed by height measurement(127 days)
- Battery of cognitive tasks(43 days)
- Plasmatic quantification of inflammatory biomarkers concentration (CRPs)(43 days)
- Plasmatic quantification of inflammatory biomarkers concentration (Interleukins1, 6 and 10)(43 days)
- Blood quantification of gut microbiome(43)
研究者
研究点 (10)
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