Randomised Placebo-controlled Venlafaxine-referenced Study of Efficacy and Safety of 5 and 10 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

Double-blind, Randomised, Placebo-controlled Study Comparing the Efficacy and Safety of Two Fixed Dosages of a Novel Antidepressant Compound to That of Placebo in Patients With Major Depressive Disorder

The purpose of this Venlafaxine-referenced study is to evaluate the efficacy, safety and tolerability of two fixed doses of Vortioxetine in the acute treatment of Major Depressive Disorder (MDD).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Vortioxetine (Lu AA21004); Drug: Placebo; Drug: Venlafaxine XL

• Study Type: Interventional
• Enrollment (Actual): 426
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• MDE as primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx)
• Current MDE duration of at least 3 months and less than 12 months
• The patient has a MADRS total score >=30

Exclusion Criteria:

• Any current psychiatric disorder other than MDD as defined in the DSM-IV TR
• Any substance disorder within the previous 6 months
• Female patients of childbearing potential who are not using effective contraception
• Use of any psychoactive medication 2 weeks prior to screening and during the study

Other protocol-defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; capsules, daily, orally
Experimental: Vortioxetine (Lu AA21004) 5 mg	Drug: Vortioxetine (Lu AA21004); encapsulated tablets, daily, orally; Other Names: Brintellix
Experimental: Vortioxetine (Lu AA21004) 10 mg	Drug: Vortioxetine (Lu AA21004); encapsulated tablets, daily, orally; Other Names: Brintellix
Other: Venlafaxine XL 225 mg; Active Reference	Drug: Venlafaxine XL; capsules, daily, orally; Other Names: Effexor®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MADRS Total Score After 6 Weeks of Treatment	The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MADRS Total Score After 1 Week of Treatment		Baseline and Week 1
Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment	The 24-item Hamilton Depression Rating Scale (HAM-D) is based on the 21-item HAM-D plus an additional 3 items (helplessness, hopelessness, and worthlessness). The observer makes his/her assessment on the basis of a specific statement, content, tone, facial expression, and gestures of the patient during the interview, and scores each item from 0 to 2 or 0 to 4. Total score from 0 to 76. The higher the score, the more severe.	Baseline and Week 6
Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment	The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56. The higher the score, the more severe.	Baseline and Week 6
Change From Baseline in CGI-S Score After 6 Weeks of Treatment	The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.	Baseline and Week 6
Change in Clinical Status Using CGI-I Score at Week 6	The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment.	Week 6
Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)		Week 6
Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)		Week 6

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012 Jun;15(5):589-600. doi: 10.1017/S1461145711001027. Epub 2011 Jul 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: February 6, 2009
• First Posted (Estimate): February 9, 2009

Study Record Updates

• Last Update Posted (Estimate): May 13, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Placebo-controlled; Acute treatment; Major depressive disorder; Multicenter study; Active reference; Randomised study
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine; Venlafaxine Hydrochloride
• Other Study ID Numbers: 11492A; 2006-001515-29 (EudraCT Number)