Trazodone Once a Day in Major Depression Disorder

Major Depressive Disorder Clinical Trial

Official title:

A Randomized, Double-blind Study Comparing the Efficacy and Safety of Trazodone OAD and Venlafaxine XR in the Treatment of Patients With Major Depressive Disorder.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02086929
• Other study ID #: 039(C)SC11063
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2014
• Last updated: December 29, 2015
• Start date: December 2012
• Est. completion date: April 2014

Study information

• Verified date: December 2015
• Source: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyAustria: Austrian Medicines and Medical Devices AgencySlovakia: State Institute for Drug ControlCzech Republic: State Institute for Drug ControlRomania: National Medicines AgencySpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

The study objective is to evaluate the efficacy and safety of trazodone OAD vs venlafaxine extended release (venlafaxine XR) after an 8-week treatment period in patients with major depressive disorder.

Description:

This randomized, venlafaxine-controlled, double-blind, parallel design study consists of a Pre-Treatment Phase (screening, wash-out) and a double-blind Treatment Phase (randomization to trazodone OAD or to venlafaxine XR, treatment for 8 weeks and tapering for 1 to 3 weeks). During the Pre-Treatment Phase, patients who sign an informed consent form will undergo initial screening. Potential candidates will be instructed to discontinue antidepressants or prohibited medications (wash-out) for a period specific to taper schedule (based on 5 elimination half-lives of the used medication). On the last day of the Pre-Treatment Phase, patients will be evaluated for the final eligibility, and those qualified will be randomly allocated in a 1:1 proportion to trazodone OAD 300 mg/day (1 week of tapering with trazodone OAD 150 mg/day) or to venlafaxine XR 75 mg/day once daily. After 3 and 5 weeks of treatment, subjects will be evaluated for the response. For non responding patients dose increases (in increments of 75 mg/day) will be done till to reach the maximum of 225 mg/day for venlafaxine XR and 450 mg/day for trazodone OAD. Patients non responding to treatment at the final visit will have their study medication tapered from 1 to 3 weeks, according to the maximum dose reached during the study. In order to prevent relapse of depression symptoms, responders at the final visit may continue the treatment. In this case, an unblinded third party Dispenser will open the treatment code and will prescribe the same medication taken by the patients during the trial, according to the formulation available on the market.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• men and women 18-75 years of age (limits included) with no limitation of race;

• outpatients;

• major depressive disorder according to DSM-IV criteria as assessed using the MINI International Neuropsychiatric Interview;

• 17-item HAMD score > 18 at both screening and baseline visits with a decrease not exceeding 20% between screening and baseline;

• symptoms of depression for at least one month before study entry (screening visit);

• legally capable to give their consent to participate the study, and available to sign and date the written informed consent prior to the inclusion in the study;

• women of childbearing potential must agree not to start a pregnancy from the signature of the informed consent up to 30 days after the last administration of the investigational product.

Exclusion Criteria:

• participation in another trial involving any investigational drug during the past 60 days;

• known hypersensitivity to venlafaxine or trazodone or their excipients;

• use of venlafaxine or trazodone within the previous six months;

• acute, or chronic, or recurrent medical conditions that might affect/jeopardize the study results;

• significant liver disease, defined as active hepatitis or elevated liver enzymes > 3 times the upper boundary of the normal range;

• significant renal disease, defined as urea and/or creatinine > 3 times the upper boundary of the normal range

• myocardial infarction within 6 months prior to start of the double blind treatment;

• positive present history of glaucoma;

• history of risk factors for Torsade de Pointes, such as heart failure, cardiac arrhythmias, bradycardia, cardiac conduction abnormalities, family history of long QT syndrome, cardiac hypertrophy, cardiomyopathy, chronic cardiac insufficiency;

• values of electrolytes (sodium, potassium, calcium, magnesium, chloride) outside the normal laboratory range and judged clinically relevant by the Investigator;

• concomitant treatment with drugs known for QT prolongation, or with drugs producing hypokalemia, or diuretics;

• QTcF values higher than 450 msec in the ECG performed at the screening;

• history of major depression resistant to medical treatments (previous failure to respond to two consecutive antidepressants of different classes used for a sufficient length of time at appropriate doses);

• history of seizure events other than a single childhood febrile seizure;

• history of alcohol or psychoactive substance abuse or addiction (except caffeine or nicotine) during the last year as defined by DSM-IV criteria;

• positive urine drug screen for CNS-active drugs (cocaine, opioids, amphetamines and cannabinoids) at Visit 1 (screening);

• acute risk of suicide (HAMD, criterion 3 with a value > 3);

• presence of any primary psychiatric disorder other than major depression;

• history or presence of bipolar disorder, any psychotic disorder, mental disorder due to general medical conditions;

• pregnancy, lactation, or female with a positive urine pregnancy test result at Visit 1 (Screening);

• electroconvulsive therapy (ECT) within 30 days prior to the screening visit;

• use of antipsychotic drugs within two months prior to the baseline visit (Visit 2);

• use of any anxiolytic or sedative hypnotic drug within seven days prior to the baseline (Visit 2) and during the study. Exception is stable low doses of benzodiazepines for insomnia (if taken by the patient more than two weeks before the Treatment Phase);

• use of any psychotropic drug or substance with central nervous system effects within seven days prior to the baseline visit (Visit 2);

• use of any non-psychotropic drug with psychotropic effects (e.g. alpha-adrenergic blockers) within seven days prior to the baseline visit (visit 2), unless a stable dose of the drug has been maintained for at least one month (three months for thyroid or hormonal medications) before the baseline visit (visit 2);

• concomitant treatment with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir);

• hyperthyroidism, even if pharmacologically corrected;

• start or discontinuation of psychotherapy within 6 weeks prior to screening;

• clinically significant abnormalities on physical examination, vital signs, ECG, laboratory tests at the screening visit;

• high blood pressure (supine systolic blood pressure > 160 mmHg or supine diastolic blood pressure > 90 mmHg) at screening or baseline, either untreated or under treatment with antihypertensives

• inability to comply with the protocol requirements, instructions and study-related restrictions; e.g. uncooperative attitude, inability to return for study-visits, and improbability of completing the clinical study;

• vulnerable subjects (e.g. persons kept in detention);

• if subject is the Investigator or his/her deputies, first grade relative, research assistant, pharmacist, study coordinator, other staff of relative thereof directly involved in the conduct of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Trazodone

• Venlafaxine

Locations

Country	Name	City	State
Austria	AKH Wien	Vienna
Austria	Institute für Psychosomatik	Vienna
Czech Republic	Saint Anne, s.r.o.	Brno-mesto
Czech Republic	SUPERVIZE, s.r.o.	Kutna Hora
Czech Republic	BIALBI s.r.o.	Litomerice
Czech Republic	Fakultni Nemocnice Olomouc, Klinika Psychiatrie	Olomouc
Czech Republic	MUDr. Eva Soukupová-Psychiatrická praxe, s.r.o.	Plzen
Czech Republic	NZZ- MUDr. Jaroslav Hronek, psychiatrická ambulance	Plzen
Czech Republic	PRAGTIS, s.r.o.	Praha 2	Praha
Czech Republic	Psychiatry Trial, s.r.o.	Praha 5	Praha
Czech Republic	MEDICAL SERVICES PRAGUE, s.r.o.	Praha 6	Praha
Czech Republic	Neuropsychiatrie s.r.o.	Praha 6	Praha
Italy	UOPI di Psichiatria Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele, Presidio "Gaspare Rodolico"	Catania
Italy	Clinica Psichiatrica Nuovo Ospedale S. Salvatore Università degli Studi del L'Aquila	L'Aquila
Italy	Ospedale Santa Maria della Misericordia Unità di Degenza Psichiatrica-SPDC	Perugia
Italy	Azienda Ospedaliera Sant'Andrea Università La Sapienza Unità Operativa Complessa di Psichiatria	Rome
Italy	AOUS-Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte Clinica Psichiatrica Universitaria	Siena
Italy	Department of Neurosciences University of Turin	Turin
Romania	Quantum Medical Center Srl	Bucharest
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"/Sectia 1	Bucharest
Romania	Spitalul clinic de psihiatrie "Prof. Dr. Al. Obregia"/Sectia 13	Bucharest
Romania	Spitalul Clinc de Urgenta Militar "Dr. Stefan Odobleja", Craiova	Craiova
Romania	Spital Clinic de Psihiatrie SOCOLA / Iasi	Iasi
Romania	Spitalul de Psihiatrie "Dr. Gh.Preda" Sibiu	Sibiu
Romania	Spitalul Clinc Judetean Mures, Centrul de Sanatate Mintala	Targu Mures
Slovakia	MENTUM, s.r.o.	Bratislava
Slovakia	Psychiatricka ambulancia	Bratislava
Slovakia	EPAMED, s.r.o.	Kosice
Slovakia	Psychiatricka nemocnica	Michalovce
Slovakia	Psycholine, s.r.o.	Rimavska Sobota
Slovakia	Psychiatricke oddelenie, NsP sv Barbory Roznava	Roznava
Spain	Instituto de Investigacion y Asistencia Psiquiatrica - IIAP	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Aziende Chimiche Riunite Angelini Francesco S.p.A

Countries where clinical trial is conducted

Austria,  Czech Republic,  Italy,  Romania,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Depression Rating Scale (HAMD) score	Mean change from baseline (Day 0) in HAMD score at Day 56.	Day 56	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) score	Mean change from baseline (Day 0) in MADRS score at Day 56.	Day 56	No
Secondary	Clinical Global Impression (CGI) Severity of Illness score	CGI-Severity of Illness improvement at Day 56.	Day 56	No
Secondary	Clinical Global Impression (CGI) Global improvement score	CGI-Global improvement at Day 56.	Day 56	No
Secondary	Percentage of responders	Rate of patients with a 50% decrease with respect to baseline on the HAMD score at Day 56.	Day 56	No
Secondary	Percentage of patients with remission	Rate of patients with a HAMD score	Day 56	No
Secondary	Safety profile of trazodone OAD compared to venlafaxine XR	Safety and tolerability will be assessed through adverse events monitoring, physical examinations and monitoring of vital signs, body weight, clinical laboratory tests, ECG.	11 weeks	Yes

External Links

•   Sponsor's website