A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication (REVIVE)

• ClinicalTrials.gov Identifier: NCT01488071
• Recruitment Status: Completed
• First Posted: December 8, 2011
• Results First Posted: March 26, 2014
• Last Update Posted: March 26, 2014
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Study Description

Brief Summary:

The objective of the present study is to evaluate whether vortioxetine (10 or 20 mg/day) is at least as effective as agomelatine (25 to 50 mg/day) in patients with depressive symptoms that showed inadequate response to Serotonin Reuptake Inhibitors (SRI) antidepressants.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Vortioxetine (Lu AA21004); Drug: Agomelatine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 495 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Parallel-group, Active-controlled, Flexible Dose Study Evaluating the Effects of [Vortioxetine] Lu AA21004 Versus Agomelatine in Adult Patients Suffering From Major Depressive Disorder With Inadequate Response to Antidepressant Treatment
• Study Start Date: January 2012
• Actual Primary Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vortioxetine 10 mg or 20 mg	Drug: Vortioxetine (Lu AA21004); encapsulated tablets, daily, orally; Other Name: Brintellix®
Active Comparator: Agomelatine 25 mg or 50 mg	Drug: Agomelatine; encapsulated tablets, daily, orally; Other Name: Valdoxan®

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in MADRS Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]
   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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Secondary Outcome Measures :

1. Change From Baseline in MADRS Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
2. Change From Baseline in HAM-A Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]
   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; higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
3. Change From Baseline in HAM-A Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]
4. Change From Baseline in CGI-S Score at Week 8 [ Time Frame: Baseline and Week 8 ]
   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. Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
5. Change From Baseline in CGI-S Score at Week 12 [ Time Frame: Baseline and Week 12 ]
6. Change in Clinical Status Using CGI-I Score at Week 8 [ Time Frame: 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. Higher score = more affected.
7. Change in Clinical Status Using CGI-I Score at Week 12 [ Time Frame: Week 12 ]
8. Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) [ Time Frame: Baseline and Week 8 ]
9. Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) [ Time Frame: Baseline and Week 12 ]
10. Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10) [ Time Frame: Week 8 ]
11. Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10) [ Time Frame: Week 12 ]
12. Change From Baseline in SDS Total Score at Week 8 [ Time Frame: Baseline and Week 8 ]
    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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
13. Change From Baseline in SDS Total Score at Week 12 [ Time Frame: Baseline and Week 12 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• The patient is being treated with a serotonin reuptake inhibitor (SRI) antidepressant (monotherapy) that was prescribed to treat Major Depressive Episode (DSM-IV-TR criteria)
• The response to the current SRI treatment is inadequate and patient agrees to discontinue the current SRI at the baseline
• Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥22 at the Screening Visit and Baseline
• The patient, if a woman, must: agree not to try to become pregnant during the study, AND use adequate, highly effective contraception

Exclusion Criteria:

• The patient has any current Axis I disorders (DSM-IV criteria) other than Major Depressive Disorder (MDD), General Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD)
• The patient is at significant risk of suicide
• The patient is currently receiving formal psychotherapy or other psychoactive medications

Other protocol-defined inclusion and exclusion criteria may apply.

Contacts and Locations

Sponsors and Collaborators

H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Papakostas GI, Nielsen RZ, Dragheim M, Tonnoir B. Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response. J Psychiatr Res. 2018 Jun;101:72-79. doi: 10.1016/j.jpsychires.2018.02.017. Epub 2018 Feb 22.

Montgomery SA, Nielsen RZ, Poulsen LH, Häggström L. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol. 2014 Sep;29(5):470-82.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01488071
• Other Study ID Numbers: 14178A; 2011-002362-21 ( EudraCT Number )
• First Posted: December 8, 2011
• Results First Posted: March 26, 2014
• Last Update Posted: March 26, 2014
• Last Verified: February 2014

Keywords provided by H. Lundbeck A/S:

Depression; Multimodal antidepressant

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Vortioxetine; S 20098; Antidepressive Agents; Psychotropic Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Hypnotics and Sedatives