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

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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:
Information provided by (Responsible Party):
H. Lundbeck A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Vortioxetine (Lu AA21004)
Drug: Agomelatine
Enrollment 495
Recruitment Details In- or outpatients who had been treated with antidepressant selective serotonin reuptake inhibitor (SSRI) or selective noradrenaline reuptake inhibitor (SNRI) monotherapy that was prescribed to treat a single episode of Major Depressive Disorder (MDD) or recurrent MDD.
Pre-assignment Details The study will consist of a screening period of 4 to 10 days before the Baseline Visit, followed by a 12-week treatment period with vortioxetine or agomelatine. A safety follow-up will be done approximately 4 weeks after the Completion/Withdrawal Visit.
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description encapsulated tablets, daily, orally encapsulated tablets, daily, orally
Period Title: Overall Study
Started 253 [1] 242 [2]
Completed 200 179
Not Completed 53 63
Reason Not Completed
Adverse Event             15             23
Lack of Efficacy             11             17
Non-compliance with study drug             2             0
Protocol Violation             5             7
Withdrawal of Consent             14             12
Lost to Follow-up             1             0
Administrative or Other Reason(s)             5             4
[1]
all-patients-treated set (APTS)
[2]
APTS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg Total
Hide Arm/Group Description encapsulated tablets, daily, orally encapsulated tablets, daily, orally Total of all reporting groups
Overall Number of Baseline Participants 253 242 495
Hide Baseline Analysis Population Description
Age and Gender: All-patients-treated set (APTS) – all patients in the APRS who took at least one dose of investigational medicinal product (IMP). Study Specific Characteristics: Full-analysis set (FAS) - all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 253 participants 242 participants 495 participants
47.0  (12.4) 45.6  (12.4) 46.3  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 253 participants 242 participants 495 participants
Female
195
  77.1%
175
  72.3%
370
  74.7%
Male
58
  22.9%
67
  27.7%
125
  25.3%
MADRS: Baseline Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 253 participants 242 participants 495 participants
29.1  (4.4) 28.7  (4.0) 28.9  (4.2)
[1]
Measure Description: 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 - 60. The higher the score, the more severe.
HAM-A: Baseline Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 253 participants 242 participants 495 participants
21.6  (6.3) 21.4  (6.2) 21.5  (6.2)
[1]
Measure Description: 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.
CGI-S Baseline Severity Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 253 participants 242 participants 495 participants
4.4  (0.6) 4.4  (0.6) 4.4  (0.6)
[1]
Measure Description: 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 patient is more ill.
SDS Total Baseline Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 253 participants 242 participants 495 participants
19.2  (5.3) 19.3  (5.2) 19.3  (5.3)
[1]
Measure Description: 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.
1.Primary Outcome
Title Change From Baseline in MADRS Total Score at Week 8
Hide Description 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.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
full-analysis set (FAS)
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 220 190
Mean (Standard Error)
Unit of Measure: units on a scale
-16.53  (0.48) -14.38  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Mixed model for repeated measurements (MMRM), using all available data, with a freely varying mean and covariance structures and with treatment, week, and site group as fixed factors and the baseline score as a covariate. The model also included interaction between week and baseline score, as well as interaction between week and treatment.

Non-inferiority, upper limit of Confidence Interval should not exceed 2.

Statistical Test of Hypothesis P-Value 0.0018
Comments Under established non-inferiority the p-value is not adjusted.
Method Mixed Models Analysis
Comments MMRM
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.16
Confidence Interval (2-Sided) 95%
-3.51 to -0.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.69
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in MADRS Total Score at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 200 178
Mean (Standard Error)
Unit of Measure: units on a scale
-18.95  (0.50) -16.92  (0.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.03
Confidence Interval (2-Sided) 95%
-3.45 to -0.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.72
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in HAM-A Total Score at Week 8
Hide Description 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.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 220 190
Mean (Standard Error)
Unit of Measure: units on a scale
-11.68  (0.39) -9.79  (0.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.89
Confidence Interval (2-Sided) 95%
-2.98 to -0.80
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.56
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in HAM-A Total Score at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 200 178
Mean (Standard Error)
Unit of Measure: units on a scale
-13.52  (0.40) -11.59  (0.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.93
Confidence Interval (2-Sided) 95%
-3.04 to -0.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.57
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in CGI-S Score at Week 8
Hide Description 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.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 220 190
Mean (Standard Error)
Unit of Measure: units on a scale
-1.84  (0.07) -1.55  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.48 to -0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in CGI-S Score at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 200 178
Mean (Standard Error)
Unit of Measure: units on a scale
-2.20  (0.07) -1.93  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0075
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.47 to -0.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change in Clinical Status Using CGI-I Score at Week 8
Hide Description 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.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 220 190
Mean (Standard Error)
Unit of Measure: units on a scale
1.97  (0.06) 2.22  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.42 to -0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Clinical Status Using CGI-I Score at Week 12
Hide Description [Not Specified]
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 200 178
Mean (Standard Error)
Unit of Measure: units on a scale
1.74  (0.06) 1.99  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.42 to -0.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Hide Description [Not Specified]
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, last observation carried forward (LOCF)
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 252 241
Measure Type: Number
Unit of Measure: percentage of participants
61.5 47.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments Wald's Test. No adjustments for multiple comparisons were made.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
1.26 to 2.60
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 252 241
Measure Type: Number
Unit of Measure: percentage of participants
69.8 56.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments Wald's Test. No adjustments for multiple comparisons were made.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
1.26 to 2.65
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10)
Hide Description [Not Specified]
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 252 241
Measure Type: Number
Unit of Measure: percentage of participants
40.5 29.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments Wald's Test. No adjustments for multiple comparisons were made.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.72
Confidence Interval (2-Sided) 95%
1.17 to 2.52
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10)
Hide Description [Not Specified]
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 252 241
Measure Type: Number
Unit of Measure: percentage of participants
55.2 39.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Wald's Test. No adjustments for multiple comparisons were made.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
1.39 to 2.90
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in SDS Total Score at Week 8
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 162 135
Mean (Standard Error)
Unit of Measure: units on a scale
-9.28  (0.53) -7.06  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.22
Confidence Interval (2-Sided) 95%
-3.63 to -0.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.72
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in SDS Total Score at Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vortioxetine 10 mg or 20 mg Agomelatine 25 mg or 50 mg
Hide Arm/Group Description:
encapsulated tablets, daily, orally
encapsulated tablets, daily, orally
Overall Number of Participants Analyzed 148 132
Mean (Standard Error)
Unit of Measure: units on a scale
-10.99  (0.55) -9.24  (0.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine 10 mg or 20 mg, Agomelatine 25 mg or 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0209
Comments No adjustments for multiple comparisons were made.
Method Mixed Models Analysis
Comments The same MMRM methodology as for the primary endpoint was used.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-3.23 to -0.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.75
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vortioxetine Agomelatine
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Vortioxetine Agomelatine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vortioxetine Agomelatine
Affected / at Risk (%) Affected / at Risk (%)
Total   3/253 (1.19%)   4/242 (1.65%) 
Gastrointestinal disorders     
Peptic ulcer perforation * 1  1/253 (0.40%)  0/242 (0.00%) 
General disorders     
Oedema peripheral * 1  1/253 (0.40%)  0/242 (0.00%) 
Investigations     
Gamma-glutamyltransferase increased * 1  0/253 (0.00%)  1/242 (0.41%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  0/253 (0.00%)  1/242 (0.41%) 
Psychiatric disorders     
Anxiety * 1  1/253 (0.40%)  0/242 (0.00%) 
Depression * 1  1/253 (0.40%)  0/242 (0.00%) 
Reproductive system and breast disorders     
Metrorrhagia * 1  0/195 (0.00%)  1/175 (0.57%) 
Social circumstances     
Social stay hospitalisation * 1  0/253 (0.00%)  1/242 (0.41%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vortioxetine Agomelatine
Affected / at Risk (%) Affected / at Risk (%)
Total   82/253 (32.41%)   77/242 (31.82%) 
Gastrointestinal disorders     
Nausea * 1  41/253 (16.21%)  22/242 (9.09%) 
Nervous system disorders     
Dizziness * 1  18/253 (7.11%)  28/242 (11.57%) 
Headache * 1  26/253 (10.28%)  32/242 (13.22%) 
Somnolence * 1  10/253 (3.95%)  19/242 (7.85%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The results of this study will be published. Authors of the primary publication based on this study must fulfil the criteria defined by the International Committee of Medical Journal Editors (ICMJE). The primary publication must be published before any secondary publications are submitted for publication.
Results Point of Contact
Name/Title: H. Lundbeck A/S
Organization: H. Lundbeck A/S
Phone: +45 36301311
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT01488071     History of Changes
Other Study ID Numbers: 14178A
2011-002362-21 ( EudraCT Number )
First Submitted: November 29, 2011
First Posted: December 8, 2011
Results First Submitted: December 19, 2013
Results First Posted: March 26, 2014
Last Update Posted: March 26, 2014