Trial Outcomes & Findings for Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder (NCT NCT01163266)

Last Updated: 2013-12-18

Results Overview

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

462 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2013-12-18

Participant Flow

Participants took part in the study at 37 investigative sites in the United States from 15 July 2010 to 17 January 2012.

Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 3 treatment groups, once a day placebo, 10 mg, or 20 mg vortioxetine.

Participant milestones

Participant milestones
Measure	Placebo Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Study STARTED	157	155	150
Overall Study Treated	157	155	150
Overall Study COMPLETED	139	124	122
Overall Study NOT COMPLETED	18	31	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Study Pretreatment Event or Adverse Event	2	9	7
Overall Study Lack of Efficacy	1	3	1
Overall Study Noncompliance with Study Drug	0	2	0
Overall Study Protocol Deviations	2	2	5
Overall Study Withdrawal of Consent	5	7	3
Overall Study Lost to Follow-up	7	7	10
Overall Study Other	1	1	2

Baseline Characteristics

Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=157 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=155 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=150 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.	Total n=462 Participants Total of all reporting groups
Age Continuous	42.3 years STANDARD_DEVIATION 11.61 • n=5 Participants	43.1 years STANDARD_DEVIATION 12.04 • n=7 Participants	43.1 years STANDARD_DEVIATION 13.09 • n=5 Participants	42.8 years STANDARD_DEVIATION 12.23 • n=4 Participants
Age, Customized ≤55 years	130 participants n=5 Participants	133 participants n=7 Participants	124 participants n=5 Participants	387 participants n=4 Participants
Age, Customized >55 years	27 participants n=5 Participants	22 participants n=7 Participants	26 participants n=5 Participants	75 participants n=4 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	118 Participants n=7 Participants	107 Participants n=5 Participants	335 Participants n=4 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	37 Participants n=7 Participants	43 Participants n=5 Participants	127 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	17 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	37 participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic and non-Latino	140 participants n=5 Participants	145 participants n=7 Participants	140 participants n=5 Participants	425 participants n=4 Participants
Race/Ethnicity, Customized Caucasian (White, including Hispanic)	120 participants n=5 Participants	106 participants n=7 Participants	97 participants n=5 Participants	323 participants n=4 Participants
Race/Ethnicity, Customized Black	37 participants n=5 Participants	43 participants n=7 Participants	49 participants n=5 Participants	129 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment United States	157 participants n=5 Participants	155 participants n=7 Participants	150 participants n=5 Participants	462 participants n=4 Participants
Height	167.46 cm STANDARD_DEVIATION 9.265 • n=5 Participants	166.86 cm STANDARD_DEVIATION 9.199 • n=7 Participants	167.92 cm STANDARD_DEVIATION 9.194 • n=5 Participants	167.41 cm STANDARD_DEVIATION 9.210 • n=4 Participants
Weight	88.28 kg STANDARD_DEVIATION 23.290 • n=5 Participants	89.00 kg STANDARD_DEVIATION 23.076 • n=7 Participants	87.08 kg STANDARD_DEVIATION 23.582 • n=5 Participants	88.13 kg STANDARD_DEVIATION 23.277 • n=4 Participants
Body Mass Index (BMI)	31.31 kg/m^2 STANDARD_DEVIATION 7.262 • n=5 Participants	31.92 kg/m^2 STANDARD_DEVIATION 7.779 • n=7 Participants	30.84 kg/m^2 STANDARD_DEVIATION 7.836 • n=5 Participants	31.36 kg/m^2 STANDARD_DEVIATION 7.622 • n=4 Participants
Waist Circumference	100.20 cm STANDARD_DEVIATION 18.640 • n=5 Participants	99.76 cm STANDARD_DEVIATION 16.996 • n=7 Participants	96.76 cm STANDARD_DEVIATION 16.434 • n=5 Participants	98.93 cm STANDARD_DEVIATION 17.426 • n=4 Participants
Smoking Classification Never smoked	65 participants n=5 Participants	82 participants n=7 Participants	77 participants n=5 Participants	224 participants n=4 Participants
Smoking Classification Current smoker	52 participants n=5 Participants	46 participants n=7 Participants	45 participants n=5 Participants	143 participants n=4 Participants
Smoking Classification Ex-smoker	40 participants n=5 Participants	27 participants n=7 Participants	28 participants n=5 Participants	95 participants n=4 Participants
Alcohol Consumption Never	54 participants n=5 Participants	63 participants n=7 Participants	52 participants n=5 Participants	169 participants n=4 Participants
Alcohol Consumption Once monthly or less often	63 participants n=5 Participants	47 participants n=7 Participants	65 participants n=5 Participants	175 participants n=4 Participants
Alcohol Consumption Once per week	22 participants n=5 Participants	21 participants n=7 Participants	19 participants n=5 Participants	62 participants n=4 Participants
Alcohol Consumption 2-to-6 times per week	15 participants n=5 Participants	21 participants n=7 Participants	14 participants n=5 Participants	50 participants n=4 Participants
Alcohol Consumption Daily	3 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	6 participants n=4 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	32.0 scores on a scale STANDARD_DEVIATION 3.99 • n=5 Participants	32.3 scores on a scale STANDARD_DEVIATION 4.52 • n=7 Participants	32.4 scores on a scale STANDARD_DEVIATION 4.30 • n=5 Participants	32.2 scores on a scale STANDARD_DEVIATION 4.27 • n=4 Participants
Hamilton Anxiety Scale Total Score	17.8 scores on a scale STANDARD_DEVIATION 5.41 • n=5 Participants	18.5 scores on a scale STANDARD_DEVIATION 5.25 • n=7 Participants	18.9 scores on a scale STANDARD_DEVIATION 5.64 • n=5 Participants	18.4 scores on a scale STANDARD_DEVIATION 5.44 • n=4 Participants
Clinical Global Impression - Severity scale score	4.5 scores on a scale STANDARD_DEVIATION 0.55 • n=5 Participants	4.5 scores on a scale STANDARD_DEVIATION 0.55 • n=7 Participants	4.5 scores on a scale STANDARD_DEVIATION 0.54 • n=5 Participants	4.5 scores on a scale STANDARD_DEVIATION 0.55 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug, and had at least 1 valid postbaseline value for assessment of primary efficacy. A mixed model for repeated measurements (MMRM) based on observed cases was used.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=124 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=122 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	-10.77 scores on a scale Standard Error 0.807	-12.96 scores on a scale Standard Error 0.832	-14.41 scores on a scale Standard Error 0.845

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set, last observation carried forward was used.

Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=155 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=154 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=148 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Percentage of Participants With a MADRS Response at Week 8	28.4 percentage of participants	33.8 percentage of participants	39.2 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Clinical Global Impression-Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score-by-week as fixed effects.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=124 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=122 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 8	2.89 scores on a scale Standard Error 0.090	2.69 scores on a scale Standard Error 0.093	2.59 scores on a scale Standard Error 0.094

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set patients with a HAM-A Baseline score ≥20. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects. The HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=52 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=57 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20	-10.26 scores on a scale Standard Error 1.392	-14.55 scores on a scale Standard Error 1.369	-17.52 scores on a scale Standard Error 1.331

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set, last observation carried forward was used.

Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=155 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=154 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=148 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Percentage of Participants in MADRS Remission at Week 8	14.2 percentage of participants	21.4 percentage of participants	22.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=89 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=77 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	-5.86 scores on a scale Standard Error 0.771	-7.25 scores on a scale Standard Error 0.747	-8.26 scores on a scale Standard Error 0.794

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 80 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 2 serious events

Other events: 103 other events

Deaths: 0 deaths

Vortioxetine 20 mg

Serious events: 0 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=157 participants at risk Placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 10 mg n=155 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Vortioxetine 20 mg n=150 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Infections and infestations Kidney infection	0.00% 0/157 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/155 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/150 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Suicide attempt	0.00% 0/157 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.65% 1/155 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/150 • A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER