Trial Outcomes & Findings for 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 (NCT NCT01140906)

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

607 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2014-02-11

Participant Flow

Patients were selected from psychiatric settings (private practices), outpatient clinics, and inpatient hospitals.

At the Baseline Visit, patients who fulfilled the selection criteria were assigned to treatment with either placebo, vortioxetine 15 or 20 mg/day, or duloxetine 60 mg/day in a 1:1:1:1 ratio.

Participant milestones

Participant milestones
Measure	Placebo capsules, daily, orally	Vortioxetine 15 mg encapsulated tablets, daily, orally	Vortioxetine 20 mg encapsulated tablets, daily, orally	Duloxetine 60 mg encapsulated capsules, daily, orally
Overall Study STARTED	158	151	151	147
Overall Study COMPLETED	133	117	125	131
Overall Study NOT COMPLETED	25	34	26	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo capsules, daily, orally	Vortioxetine 15 mg encapsulated tablets, daily, orally	Vortioxetine 20 mg encapsulated tablets, daily, orally	Duloxetine 60 mg encapsulated capsules, daily, orally
Overall Study Adverse Event	7	10	17	7
Overall Study Lack of Efficacy	6	8	2	1
Overall Study Non-compliance	0	1	0	1
Overall Study Protocol Violation	5	3	2	1
Overall Study Withdrawal of consent	6	6	2	2
Overall Study Lost to Follow-up	1	1	0	2
Overall Study Administrative or other reason	0	5	3	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=158 Participants capsules, daily, orally	Vortioxetine 15 mg n=151 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=151 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=147 Participants encapsulated capsules, daily, orally	Total n=607 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 13.1 • n=5 Participants	47.0 years STANDARD_DEVIATION 14.6 • n=7 Participants	46.2 years STANDARD_DEVIATION 13.4 • n=5 Participants	45.6 years STANDARD_DEVIATION 13.6 • n=4 Participants	46.7 years STANDARD_DEVIATION 13.7 • n=21 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	97 Participants n=7 Participants	91 Participants n=5 Participants	102 Participants n=4 Participants	400 Participants n=21 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	54 Participants n=7 Participants	60 Participants n=5 Participants	45 Participants n=4 Participants	207 Participants n=21 Participants
MADRS baseline total score	31.5 units on a scale STANDARD_DEVIATION 3.6 • n=5 Participants	31.8 units on a scale STANDARD_DEVIATION 3.4 • n=7 Participants	31.2 units on a scale STANDARD_DEVIATION 3.4 • n=5 Participants	31.2 units on a scale STANDARD_DEVIATION 3.5 • n=4 Participants	31.4 units on a scale STANDARD_DEVIATION 3.5 • n=21 Participants
CGI-S baseline severity score	4.9 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	4.9 units on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	4.8 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	4.8 units on a scale STANDARD_DEVIATION 0.7 • n=4 Participants	4.8 units on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
HAM-A baseline total score	20.8 units on a scale STANDARD_DEVIATION 6.6 • n=5 Participants	21.3 units on a scale STANDARD_DEVIATION 6.8 • n=7 Participants	20.4 units on a scale STANDARD_DEVIATION 6.9 • n=5 Participants	20.5 units on a scale STANDARD_DEVIATION 6.7 • n=4 Participants	20.8 units on a scale STANDARD_DEVIATION 6.7 • n=21 Participants
SDS total baseline score	19.8 units on a scale STANDARD_DEVIATION 6.0 • n=5 Participants	20.6 units on a scale STANDARD_DEVIATION 5.3 • n=7 Participants	20.7 units on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	20.5 units on a scale STANDARD_DEVIATION 4.4 • n=4 Participants	20.4 units on a scale STANDARD_DEVIATION 5.2 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: Full-analysis set (FAS), mixed model for repeated measurements (MMRM)

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.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants capsules, daily, orally	Vortioxetine 15 mg n=149 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=151 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=146 Participants encapsulated capsules, daily, orally
Change From Baseline in MADRS Total Score After 8 Weeks of Treatment.	-11.70 units on a scale Standard Error 0.76	-17.23 units on a scale Standard Error 0.79	-18.79 units on a scale Standard Error 0.78	-21.15 units on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Week 8

Population: FAS, last observation carried forward (LOCF), Logistic Regression

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants capsules, daily, orally	Vortioxetine 15 mg n=149 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=151 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=146 Participants encapsulated capsules, daily, orally
Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)	32 percentage of patients	57 percentage of patients	62 percentage of patients	74 percentage of patients

SECONDARY outcome

Timeframe: Week 8

Population: FAS, MMRM

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.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants capsules, daily, orally	Vortioxetine 15 mg n=149 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=151 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=146 Participants encapsulated capsules, daily, orally
Change in Clinical Status Using CGI-I Score at Week 8	2.86 units on a scale Standard Error 0.09	2.18 units on a scale Standard Error 0.09	1.92 units on a scale Standard Error 0.09	1.75 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS, MMRM

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants capsules, daily, orally	Vortioxetine 15 mg n=87 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=80 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=80 Participants encapsulated capsules, daily, orally
Change From Baseline in MADRS Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score ≥20	-12.20 units on a scale Standard Error 1.09	-17.44 units on a scale Standard Error 1.08	-18.62 units on a scale Standard Error 1.15	-20.91 units on a scale Standard Error 1.10

SECONDARY outcome

Timeframe: Week 8

Population: FAS, LOCF, Logistic Regression

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants capsules, daily, orally	Vortioxetine 15 mg n=149 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=151 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=146 Participants encapsulated capsules, daily, orally
Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10)	19 percentage of patients	35 percentage of patients	38 percentage of patients	54 percentage of patients

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS, MMRM

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.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants capsules, daily, orally	Vortioxetine 15 mg n=97 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=107 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=99 Participants encapsulated capsules, daily, orally
Change From Baseline in SDS Total Score After 8 Weeks of Treatment	-4.46 units on a scale Standard Error 0.82	-7.70 units on a scale Standard Error 0.89	-8.38 units on a scale Standard Error 0.85	-11.39 units on a scale Standard Error 0.85

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: FAS, MMRM

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.

Outcome measures

Outcome measures
Measure	Placebo n=156 Participants capsules, daily, orally	Vortioxetine 15 mg n=147 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=148 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=144 Participants encapsulated capsules, daily, orally
Change From Baseline in ASEX Total Score After 8 Weeks of Treatment	0.28 units on a scale Standard Error 0.42	-0.39 units on a scale Standard Error 0.43	-0.20 units on a scale Standard Error 0.43	-1.25 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Change from Week 8 in DESS total score analyzed at Week 10

Population: All Patients Completed Set (APCS), OC, Analysis of Covariance (ANCOVA)

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.

Outcome measures

Outcome measures
Measure	Placebo n=121 Participants capsules, daily, orally	Vortioxetine 15 mg n=116 Participants encapsulated tablets, daily, orally	Vortioxetine 20 mg n=120 Participants encapsulated tablets, daily, orally	Duloxetine 60 mg n=127 Participants encapsulated capsules, daily, orally
Potential Discontinuation Symptoms After Abrupt Discontinuation of Treatment With Vortioxetine	0.15 units on a scale Standard Error 0.30	0.01 units on a scale Standard Error 0.31	0.72 units on a scale Standard Error 0.31	2.28 units on a scale Standard Error 0.30

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Vortioxetine 15 mg

Serious events: 0 serious events

Other events: 61 other events

Deaths: 0 deaths

Vortioxetine 20 mg

Serious events: 2 serious events

Other events: 70 other events

Deaths: 0 deaths

Duloxetine 60 mg

Serious events: 3 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=158 participants at risk	Vortioxetine 15 mg n=151 participants at risk	Vortioxetine 20 mg n=151 participants at risk	Duloxetine 60 mg n=147 participants at risk
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.68% 1/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.68% 1/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Investigations Blood pressure decreased	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.66% 1/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Nervous system disorders Dizziness	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.66% 1/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Psychiatric disorders Intentional self-injury	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.66% 1/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Psychiatric disorders Self injurious behaviour	0.00% 0/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.68% 1/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/110 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/97 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/91 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.98% 1/102 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period

Other adverse events

Other adverse events
Measure	Placebo n=158 participants at risk	Vortioxetine 15 mg n=151 participants at risk	Vortioxetine 20 mg n=151 participants at risk	Duloxetine 60 mg n=147 participants at risk
Gastrointestinal disorders Diarrhoea	3.8% 6/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	4.0% 6/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	7.3% 11/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	6.1% 9/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Gastrointestinal disorders Dry mouth	3.2% 5/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	3.3% 5/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	6.0% 9/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	9.5% 14/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Gastrointestinal disorders Nausea	10.1% 16/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	26.5% 40/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	31.8% 48/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	30.6% 45/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
General disorders Fatigue	2.5% 4/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	4.0% 6/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	3.3% 5/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	5.4% 8/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Nervous system disorders Dizziness	6.3% 10/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	4.6% 7/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	4.6% 7/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	10.2% 15/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Nervous system disorders Headache	7.6% 12/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	10.6% 16/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	12.6% 19/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	10.9% 16/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period
Skin and subcutaneous tissue disorders Hyperhidrosis	3.8% 6/158 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	3.3% 5/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	0.00% 0/151 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period	7.5% 11/147 • Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period

Additional Information

H. Lundbeck A/S

Phone: +45 3630 1311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of this study will be published at the discretion of H. Lundbeck A/S. H. Lundbeck A/S will ensure that the authorship of all publications based on this study is in accordance with the criteria defined by the International Committee of Medical Journal Editors (ICMJE). The primary publication must be published before any secondary publications.
Publication restrictions are in place

Restriction type: OTHER