Randomised Placebo-controlled Duloxetine-referenced Study of Efficacy and Safety of 15 and 20 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Lu AA21004 (15 and 20 mg/Day) in the Acute Treatment of Adult Patients With Major Depressive Disorder

The purpose of the study is to evaluate the efficacy, tolerability and the safety of two fixed doses of vortioxetine in the treatment of major depressive disorder.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 607
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has recurrent MDD as the primary diagnosis according to DSM-IV-TR™ criteria (classification code 296.3x)
• The patient has a MADRS total score >=26
• The patient has a CGI-S score >=4
• The patient has had the current episode of MDE for >3 months

Exclusion Criteria:

• Any current anxiety psychiatric disorder as defined in the DSM-IV TR
• Current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV TR
• Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV TR
• Use of any psychoactive medication 2 weeks prior to screening and during the study
• The patient is at significant risk of suicide or has a score >=5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit

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: 15 mg	Drug: Vortioxetine (Lu AA21004); encapsulated tablets, daily, orally; Other Names: Brintellix
Experimental: Vortioxetine: 20 mg	Drug: Vortioxetine (Lu AA21004); encapsulated tablets, daily, orally; Other Names: Brintellix
Other: Duloxetine: 60 mg; Active Reference	Drug: Duloxetine; encapsulated capsules, daily, orally; Other Names: Cymbalta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MADRS Total Score After 8 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 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)		Week 8
Change in Clinical Status Using CGI-I Score at Week 8	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 8
Change From Baseline in MADRS Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score ≥20		Baseline and Week 8
Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10)		Week 8
Change From Baseline in SDS Total Score After 8 Weeks of Treatment	The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe.	Baseline and Week 8
Change From Baseline in ASEX Total Score After 8 Weeks of Treatment	The Arizona Sexual Experience Scale (ASEX) is a 5-item, patient self-rated scale that evaluates a patient's recent sexual experience. Patients are asked to assess their own experience over the last week (for example, "How strong is your sex drive?", "Are your orgasms satisfying?") and respond on a 6-point scale for each item. The ASEX is used to identify individuals with sexual dysfunction. Possible total score ranges from 5 to 30, with the higher score indicating more patient sexual dysfunction. A negative change indicates a lower sexual dysfunction.	Baseline and Week 8
Potential Discontinuation Symptoms After Abrupt Discontinuation of Treatment With Vortioxetine	The Discontinuation-Emergent Signs and Symptoms Scale (DESS) was designed to evaluate possible effects of discontinuation of antidepressant therapy. It is a clinician-rated instrument that queries for signs and symptoms on a 43-item checklist (for example, agitation, insomnia, fatigue, and dizziness) to assess whether the item (event) is discontinuation-emergent. A new or worsened event reported after discontinuation of therapy scores 1 point on the checklist, and the DESS total score is the sum of all positive scores on the checklist. A higher score indicates more symptoms.	Change from Week 8 in DESS total score analyzed at Week 10

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.
• Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.
• Belzeaux R, Gorgievski V, Fiori LM, Lopez JP, Grenier J, Lin R, Nagy C, Ibrahim EC, Gascon E, Courtet P, Richard-Devantoy S, Berlim M, Chachamovich E, Theroux JF, Dumas S, Giros B, Rotzinger S, Soares CN, Foster JA, Mechawar N, Tall GG, Tzavara ET, Kennedy SH, Turecki G. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nat Commun. 2020 Apr 2;11(1):1635. doi: 10.1038/s41467-020-15423-5.
• Belzeaux R, Fiori LM, Lopez JP, Boucekine M, Boyer L, Blier P, Farzan F, Frey BN, Giacobbe P, Lam RW, Leri F, MacQueen GM, Milev R, Muller DJ, Parikh SV, Rotzinger S, Soares CN, Uher R, Foster JA, Kennedy SH, Turecki G. Predicting Worsening Suicidal Ideation With Clinical Features and Peripheral Expression of Messenger RNA and MicroRNA During Antidepressant Treatment. J Clin Psychiatry. 2019 May 7;80(3):18m12556. doi: 10.4088/JCP.18m12556.
• Boulenger JP, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014 May;29(3):138-49. doi: 10.1097/YIC.0000000000000018.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 9, 2010
• First Posted (Estimate): June 10, 2010

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: December 23, 2013
• Last Verified: December 1, 2013

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; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Duloxetine Hydrochloride; Vortioxetine
• Other Study ID Numbers: 13267A; 2009-017523-26 (EudraCT Number)