Exploratory study of the efficacy and safety of flexible doses of Milnacipran and Venlafaxine administered in out patients with Major Depressive Disorder.

Phase 1

• Conditions: Major Depressive Disorder; MedDRA version: 8.1 Level: LLT Classification code 10012378 Term: Depression

• Registration Number: EUCTR2006-003658-47-FR
• Lead Sponsor: Pierre Fabre Médicament - IRPF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-08-25
• Study Completion: 2008-04-15
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 180

Inclusion Criteria

- Out patient, aged 18 years to 70 years
- Male, or female of childbearing potential using a medically accepted and well documented method of contraception (e.g. oral contraceptives, intrauterine devices, patch, contraceptive implant...) during 2 months before the inclusion in the study, documented sterility or postmenopause (one year amenorrhoea)
- Meeting DSM IV-TR criteria for Major Depressive Disorder diagnosed using a structured interview (MINI) moderate or severe, recurrent, unipolar, without psychotic features
- Total score MADRS > or = to 23 at selection and inclusion visits
- Without any clinically relevant abnormalities in clinical examination, laboratory tests and ECG parameters
- Patient having signed the written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Psychiatric criteria

- Patient at significant suicidal risk as assessed with the MINI 5.0.0 - section C
- Resistance to two well-conducted antidepressant treatments (defined by the lack of response to at least two treatments prescribed at their optimal dose and during at least 4 weeks) for the current episode
- Any history of psychotic episode or disorder
- Any history of bipolar disorder
- Any current panic disorder, agoraphobia, or obsessive compulsive disorder, generalised anxiety disorder or post traumatic stress disorder whose onset preceded the onset of the depressive disorder (diagnosis confirmed with MINI) .
- Current major personality disorder of clinical significance or any other condition that might affect compliance (Cluster A, B and C ex: borderline, paranoid, histrionic, avoidant…)
- History of alcohol and/or drug abuse and/or dependence, except tobacco according to DSM IV-TR criteria in the 12 months preceding inclusion

Somatic criteria

- Severe underlying or ongoing systemic disease that could interfere with the study
- Fibromyalgia or chronic fatigue
- Previous history of generalised or partial seizure
- Organic cerebral disease
- Known closed angle glaucoma
- Cardiovascular disease including recent myocardial infarction, cardiac failure, post stroke, uncontrolled arterial hypertension
- Known cardiac rhythm or conduction disorder
- Hepatic insufficiency
- Known prostatic disorder and/or dysuria
- Renal failure
- Pregnancy or breast-feeding
- Gastrointestinal disorders (due to glucose and galactose malabsorption or lactase deficit) or congenital galactosemia
- History of hemostasis disorders.

Laboratory criteria

- AST/SGOT and ALT/SGPT greater than 1.5 times the upper normal values
- Creatinine > 150 µmol/L or documented creatinine clearence< 60 ml/min
- Positive pregnancy test
- Clinically relevant abnormal values according to the investigator's opinion for the other laboratory parameters

ECG criteria

- QT or QTc greater than the upper limit of the normal range
- Clinically relevant abnormal values according to the investigator's opinion for the other ECG parameters

Treatment related criteria

- Known hypersensitivity or allergy to one of the study treatments
- Non-response to milnacipran or venlafaxine for a previous episode
- Previous treatment with Milnacipran or Venlafaxine for this episode
- Patient involved in any other biomedical research currently or within the past 3 months
- Electroconvulsive therapy in the 3 months preceding inclusion
- Structured psychotherapy initiated within the past 6 weeks
- Treatment with a depot-neuroleptic during the past 12 months
- Chronic use (at least 5 days per week) of benzodiazepines in the past 3 months or initiation within the 3 months prior to D1, at doses strictly superior to 10 mg diazepam/day equivalent.
- Chronic use (at least 5 days

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To assess the percentage of responders in both treatment groups, Milnacipran or Venlafaxine administered up to 200 mg/day in flexible doses, during a treatment period of 8 weeks including up-titration, in out patients with Major Depressive Disorder.;<br> Secondary Objective: - To assess safety in each treatment group.<br> - To assess pain and anxiety symptoms associated with Major Depressive Disorder.<br> ;<br> Primary end point(s): Primary efficacy criterion:<br><br> Decrease of 50.0% or more of the total score of MADRS between inclusion and last visit performed at the end of the treatment period at fixed dose (D56 or visit of premature withdrawal)<br>