Randomised Placebo-controlled Duloxetine-referenced Efficacy and Safety Study of 2.5, 5 and 10 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder

A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Three Dosages of [Vortioxetine] Lu AA21004, in Acute Treatment of Major Depressive Disorder

The purpose of the study is to evaluate the efficacy and the tolerability of three fixed doses of Vortioxetine in order to establish the appropriate clinical effective dose range in the treatment of Major Depressive Disorder (MDD).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 766
• 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:

• MDE as primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx)
• Moderate to severe depression
• Current MDE duration of at least 3 months

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; capsules; daily; orally
Experimental: Vortioxetine: 2.5 mg	Drug: Vortioxetine (Lu AA21004); 2.5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 10 mg/day; encapsulated tablets; orally; Other Names: Brintellix
Experimental: Vortioxetine: 5 mg	Drug: Vortioxetine (Lu AA21004); 2.5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 10 mg/day; encapsulated tablets; orally; Other Names: Brintellix
Experimental: Vortioxetine: 10 mg	Drug: Vortioxetine (Lu AA21004); 2.5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 5 mg/day; encapsulated tablets; orally; Other Names: Brintellix; Drug: Vortioxetine (Lu AA21004); 10 mg/day; encapsulated tablets; orally; Other Names: Brintellix
Other: Duloxetine: 60 mg; Active reference	Drug: Duloxetine; 60 mg/day; encapsulated capsules; 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
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
Change From Baseline in HAM-D-24 Total Score After 8 Weeks of Treatment	The Hamilton Depression Scale - 24 Items (HAM-D-24) measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 76. The higher the score, the more severe.	Baseline and Week 8
Change From Baseline in HAM-A Total Score After 8 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 8
Change From Baseline in CGI-S Score After 8 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 8
Change From Baseline in HAM-D-24 Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score >=20		Baseline and Week 8

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.
• Baldwin DS, Loft H, Dragheim M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol. 2012 Jul;22(7):482-91. doi: 10.1016/j.euroneuro.2011.11.008. Epub 2011 Dec 30.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 3, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimate): March 13, 2008

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: 11984A; EudraCT 2007-001870-95 (Registry Identifier: EudraCT)