Trial Outcomes & Findings for A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication (NCT NCT01488071)

NCT ID: NCT01488071

Last Updated: 2014-03-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 495 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2014-03-26

Participant Flow

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.

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.

Participant milestones

Measure	Vortioxetine 10 mg or 20 mg encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg encapsulated tablets, daily, orally
Overall Study STARTED	253	242
Overall Study COMPLETED	200	179
Overall Study NOT COMPLETED	53	63

Reasons for withdrawal

Measure	Vortioxetine 10 mg or 20 mg encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg encapsulated tablets, daily, orally
Overall Study Adverse Event	15	23
Overall Study Lack of Efficacy	11	17
Overall Study Non-compliance with study drug	2	0
Overall Study Protocol Violation	5	7
Overall Study Withdrawal of Consent	14	12
Overall Study Lost to Follow-up	1	0
Overall Study Administrative or Other Reason(s)	5	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vortioxetine 10 mg or 20 mg n=253 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=242 Participants encapsulated tablets, daily, orally	Total n=495 Participants Total of all reporting groups
Age, Continuous	47.0 years STANDARD_DEVIATION 12.4 • n=5 Participants	45.6 years STANDARD_DEVIATION 12.4 • n=7 Participants	46.3 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	195 Participants n=5 Participants	175 Participants n=7 Participants	370 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	67 Participants n=7 Participants	125 Participants n=5 Participants
MADRS: Baseline Total Score	29.1 units on a scale STANDARD_DEVIATION 4.4 • n=5 Participants	28.7 units on a scale STANDARD_DEVIATION 4.0 • n=7 Participants	28.9 units on a scale STANDARD_DEVIATION 4.2 • n=5 Participants
HAM-A: Baseline Total Score	21.6 units on a scale STANDARD_DEVIATION 6.3 • n=5 Participants	21.4 units on a scale STANDARD_DEVIATION 6.2 • n=7 Participants	21.5 units on a scale STANDARD_DEVIATION 6.2 • n=5 Participants
CGI-S Baseline Severity Score	4.4 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	4.4 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	4.4 units on a scale STANDARD_DEVIATION 0.6 • n=5 Participants
SDS Total Baseline Score	19.2 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants	19.3 units on a scale STANDARD_DEVIATION 5.2 • n=7 Participants	19.3 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: full-analysis set (FAS)

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.

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=220 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=190 Participants encapsulated tablets, daily, orally
Change From Baseline in MADRS Total Score at Week 8	-16.53 units on a scale Standard Error 0.48	-14.38 units on a scale Standard Error 0.51

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=200 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=178 Participants encapsulated tablets, daily, orally
Change From Baseline in MADRS Total Score at Week 12	-18.95 units on a scale Standard Error 0.50	-16.92 units on a scale Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS

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.

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=220 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=190 Participants encapsulated tablets, daily, orally
Change From Baseline in HAM-A Total Score at Week 8	-11.68 units on a scale Standard Error 0.39	-9.79 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=200 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=178 Participants encapsulated tablets, daily, orally
Change From Baseline in HAM-A Total Score at Week 12	-13.52 units on a scale Standard Error 0.40	-11.59 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS

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.

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=220 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=190 Participants encapsulated tablets, daily, orally
Change From Baseline in CGI-S Score at Week 8	-1.84 units on a scale Standard Error 0.07	-1.55 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=200 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=178 Participants encapsulated tablets, daily, orally
Change From Baseline in CGI-S Score at Week 12	-2.20 units on a scale Standard Error 0.07	-1.93 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 8

Population: FAS

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.

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=220 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=190 Participants encapsulated tablets, daily, orally
Change in Clinical Status Using CGI-I Score at Week 8	1.97 units on a scale Standard Error 0.06	2.22 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 12

Population: FAS

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=200 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=178 Participants encapsulated tablets, daily, orally
Change in Clinical Status Using CGI-I Score at Week 12	1.74 units on a scale Standard Error 0.06	1.99 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS, last observation carried forward (LOCF)

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=252 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=241 Participants encapsulated tablets, daily, orally
Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)	61.5 percentage of participants	47.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS, LOCF

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=252 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=241 Participants encapsulated tablets, daily, orally
Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)	69.8 percentage of participants	56.0 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS, LOCF

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=252 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=241 Participants encapsulated tablets, daily, orally
Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10)	40.5 percentage of participants	29.5 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS, LOCF

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=252 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=241 Participants encapsulated tablets, daily, orally
Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10)	55.2 percentage of participants	39.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS

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.

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=162 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=135 Participants encapsulated tablets, daily, orally
Change From Baseline in SDS Total Score at Week 8	-9.28 units on a scale Standard Error 0.53	-7.06 units on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS

Outcome measures

Measure	Vortioxetine 10 mg or 20 mg n=148 Participants encapsulated tablets, daily, orally	Agomelatine 25 mg or 50 mg n=132 Participants encapsulated tablets, daily, orally
Change From Baseline in SDS Total Score at Week 12	-10.99 units on a scale Standard Error 0.55	-9.24 units on a scale Standard Error 0.58

Adverse Events

Vortioxetine

Serious events: 3 serious events

Other events: 82 other events

Deaths: 0 deaths

Agomelatine

Serious events: 4 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vortioxetine n=253 participants at risk	Agomelatine n=242 participants at risk
Gastrointestinal disorders Peptic ulcer perforation	0.40% 1/253	0.00% 0/242
General disorders Oedema peripheral	0.40% 1/253	0.00% 0/242
Investigations Gamma-glutamyltransferase increased	0.00% 0/253	0.41% 1/242
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/253	0.41% 1/242
Psychiatric disorders Anxiety	0.40% 1/253	0.00% 0/242
Psychiatric disorders Depression	0.40% 1/253	0.00% 0/242
Reproductive system and breast disorders Metrorrhagia	0.00% 0/195	0.57% 1/175
Social circumstances Social stay hospitalisation	0.00% 0/253	0.41% 1/242

Other adverse events

Measure	Vortioxetine n=253 participants at risk	Agomelatine n=242 participants at risk
Gastrointestinal disorders Nausea	16.2% 41/253	9.1% 22/242
Nervous system disorders Dizziness	7.1% 18/253	11.6% 28/242
Nervous system disorders Headache	10.3% 26/253	13.2% 32/242
Nervous system disorders Somnolence	4.0% 10/253	7.9% 19/242

Additional Information

H. Lundbeck A/S

H. Lundbeck A/S

Phone: +45 36301311

Email: LundbeckClinicalTrials@lundbeck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER