Trial Outcomes & Findings for Safety and Tolerability of Vortioxetine (LuAA21004) - Open Label Extension Study (NCT NCT01152996)

NCT ID: NCT01152996

Last Updated: 2014-05-28

Results Overview

Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1075 participants
• Primary outcome timeframe: Over the 52 week period
• Results posted on: 2014-05-28

Participant Flow

Participants took part in the study at 143 investigative sites in the United States from 07 Sep 2010 to 31 May 2013.

Patients who completed Studies LuAA21004_315 (NCT01153009), LuAA21004_316 (NCT01163266), and LuAA21004_317 (NCT01179516) and were willing to continue, and judged by the investigator to benefit from a 52-week continuation treatment with Lu AA21004, were enrolled and received flexible doses of study drug, based on patient response and tolerability.

Participant milestones

Measure	Vortioxetine Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Overall Study STARTED	1075
Overall Study Treated	1073
Overall Study COMPLETED	538
Overall Study NOT COMPLETED	537

Reasons for withdrawal

Measure	Vortioxetine Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Overall Study Withdrawal by Subject	142
Overall Study Adverse Event	115
Overall Study Lost to Follow-up	112
Overall Study Lack of Efficacy	68
Overall Study Noncompliance	41
Overall Study Other	36
Overall Study Protocol Violation	22
Overall Study Elevated liver enzymes	1

Baseline Characteristics

Safety and Tolerability of Vortioxetine (LuAA21004) - Open Label Extension Study

Baseline characteristics by cohort

Measure	Vortioxetine n=1075 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Age, Continuous	44.5 years STANDARD_DEVIATION 12.05 • n=5 Participants
Sex: Female, Male Female	790 Participants n=5 Participants
Sex: Female, Male Male	285 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian (or White, including Hispanic)	813 participants n=5 Participants
Race/Ethnicity, Customized Black/African American	249 participants n=5 Participants
Race/Ethnicity, Customized Asian	7 participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	5 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	104 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and Non-Latino	971 participants n=5 Participants
Weight	88.77 kg) STANDARD_DEVIATION 24.160 • n=5 Participants
Body Mass Index (BMI)	31.60 kg/m^2 STANDARD_DEVIATION 8.061 • n=5 Participants
Height	167.44 cm STANDARD_DEVIATION 9.456 • n=5 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	20.0 scores on a scale STANDARD_DEVIATION 10.70 • n=5 Participants
Hamilton Anxiety Scale (HAM-A) total score	11.6 scores on a scale STANDARD_DEVIATION 6.65 • n=5 Participants
Clinical Global Impression - Severity scale (CGI-S) score	3.3 scores on a scale STANDARD_DEVIATION 1.21 • n=5 Participants

PRIMARY outcome

Timeframe: Over the 52 week period

Population: Safety set

Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.

Outcome measures

Measure	Vortioxetine n=1073 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Weight increased	65 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Nausea	258 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Diarrhea	80 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Vomiting	68 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Constipation	65 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Nasopharyngitis	68 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Viral upper respiratory tract infection	66 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Upper respiratory tract infection	60 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Headache	136 participants
Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% Insomnia	56 participants

PRIMARY outcome

Timeframe: Over the 52 week period

Population: Safety set

Serious treatment-emergent adverse events (serious-TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A serious-TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. Serious Adverse Events include adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered serious adverse events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned.

Outcome measures

Measure	Vortioxetine n=1073 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Number of Participants With Serious Treatment-Emergent Adverse Events	29 participants

PRIMARY outcome

Timeframe: Over the 52 week period

Population: Safety set

Treatment-emergent adverse events are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.

Outcome measures

Measure	Vortioxetine n=1073 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Treatment-Emergent Adverse Events Leading to Study Discontinuation	117 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44, and 52

Population: Safety set, observed cases (OC)

The change between MADRS total score at each assessed visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.

Outcome measures

Measure	Vortioxetine n=1043 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 2 (n=1043)	-4.8 units on a scale Standard Deviation 7.50
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 16 (n=777)	-9.1 units on a scale Standard Deviation 9.50
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 20 (n=747)	-9.4 units on a scale Standard Deviation 10.03
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 1 (n=1043)	-2.7 units on a scale Standard Deviation 6.32
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 4 (n=1004)	-6.1 units on a scale Standard Deviation 8.50
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 8 (n=936)	-7.9 units on a scale Standard Deviation 9.19
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 12 (n=843)	-8.5 units on a scale Standard Deviation 9.55
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 24 (n=697)	-9.7 units on a scale Standard Deviation 9.64
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 28 (n=670)	-9.5 units on a scale Standard Deviation 10.20
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 36 (n=617)	-9.7 units on a scale Standard Deviation 10.44
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 44 (n=573)	-10.3 units on a scale Standard Deviation 10.70
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Week 52 (n=534)	-10.3 units on a scale Standard Deviation 11.00

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 24, and 52

Population: Safety set, observed cases (OC)

The change between HAM-A score at each assessed visit and HAM-A score at baseline. HAM-A is a 14 item rating scale to quantify anxiety symptomatology severity (i.e., anxious mood, tension, fear, insomnia, etc.) rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56. Higher scores indicate greater severity of symptoms.

Outcome measures

Measure	Vortioxetine n=1029 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score Week 52 (n=548)	-4.8 units on a scale Standard Deviation 6.52
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score Week 4 (n=1029)	-2.6 units on a scale Standard Deviation 4.98
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score Week 24 (n=742)	-4.2 units on a scale Standard Deviation 5.84

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 24, and 52

Population: Safety set, observed cases (OC)

The change between CGI-S score at each assessed visit and CGI-S score at baseline. The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill). Higher scores indicate greater severity of illness.

Outcome measures

Measure	Vortioxetine n=1030 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 4 (n=1030)	-0.6 units on a scale Standard Deviation 0.99
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 24 (n=743)	-1.0 units on a scale Standard Deviation 1.16
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 52 (n=549)	-1.2 units on a scale Standard Deviation 1.32

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, and 52

Population: Safety set, observed cases (OC)

The change between the SDS total score at each assessed visit and the total score collected at baseline. The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment.

Outcome measures

Measure	Vortioxetine n=650 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score Week 12 (n=650)	-2.8 units on a scale Standard Deviation 6.69
Change From Baseline in Sheehan Disability Scale (SDS) Total Score Week 24 (n=494)	-3.9 units on a scale Standard Deviation 6.88
Change From Baseline in Sheehan Disability Scale (SDS) Total Score Week 36 (n=414)	-4.0 units on a scale Standard Deviation 7.37
Change From Baseline in Sheehan Disability Scale (SDS) Total Score Week 52 (n=381)	-4.7 units on a scale Standard Deviation 7.11

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, and 52

Population: Safety set, observed cases (OC)

The change between the Sheehan Disability work/school subscale score at each assessed visit and work/school subscale score collected at baseline. The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely). Higher scores indicate greater severity of impairment.

Outcome measures

Measure	Vortioxetine n=650 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in SDS Work/School Subscale Week 12 (n=650)	-0.8 units on a scale Standard Deviation 2.42
Change From Baseline in SDS Work/School Subscale Week 24 (n=494)	-1.2 units on a scale Standard Deviation 2.48
Change From Baseline in SDS Work/School Subscale Week 36 (n=414)	-1.2 units on a scale Standard Deviation 2.60
Change From Baseline in SDS Work/School Subscale Week 52 (n=381)	-1.4 units on a scale Standard Deviation 2.61

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, and 52

Population: Safety set, observed cases (OC)

The change between the Sheehan Disability social life subscale score at each assessed visit and social life subscale score collected at baseline. The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely). Higher scores indicate greater severity of impairment.

Outcome measures

Measure	Vortioxetine n=942 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in SDS Social Life Subscale Week 12 (n=942)	-1.0 units on a scale Standard Deviation 2.53
Change From Baseline in SDS Social Life Subscale Week 24 (n=721)	-1.4 units on a scale Standard Deviation 2.55
Change From Baseline in SDS Social Life Subscale Week 36 (n=617)	-1.4 units on a scale Standard Deviation 2.82
Change From Baseline in SDS Social Life Subscale Week 52 (n=545)	-1.6 units on a scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: Baseline and Weeks 12, 24, 36, and 52

Population: Safety set, observed cases (OC)

The change between the Sheehan Disability family life/home responsibilities subscale score at each assessed visit and family life/home responsibilities subscale score collected at baseline. The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely). Higher scores indicate greater severity of impairment.

Outcome measures

Measure	Vortioxetine n=942 Participants Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Change From Baseline in SDS Family Life/Home Responsibilities Subscale Week 12 (n=942)	-0.9 units on a scale Standard Deviation 2.39
Change From Baseline in SDS Family Life/Home Responsibilities Subscale Week 24 (n=721)	-1.3 units on a scale Standard Deviation 2.47
Change From Baseline in SDS Family Life/Home Responsibilities Subscale Week 36 (n=617)	-1.4 units on a scale Standard Deviation 2.74
Change From Baseline in SDS Family Life/Home Responsibilities Subscale Week 52 (n=545)	-1.6 units on a scale Standard Deviation 2.76

Adverse Events

Vortioxetine

Serious events: 29 serious events

Other events: 854 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vortioxetine n=1073 participants at risk Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Cardiac disorders Atrial fibrillation	0.09% 1/1073 • 56 weeks 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.
Gastrointestinal disorders Abdominal pain	0.09% 1/1073 • 56 weeks 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.
Gastrointestinal disorders Esophageal rupture	0.09% 1/1073 • 56 weeks 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.
Hepatobiliary disorders Cholecystitis acute	0.19% 2/1073 • 56 weeks 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.
Hepatobiliary disorders Cholecystitis	0.09% 1/1073 • 56 weeks 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.
Hepatobiliary disorders Cholelithiasis	0.09% 1/1073 • 56 weeks 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.
Infections and infestations Anal abscess	0.09% 1/1073 • 56 weeks 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.
Infections and infestations Latent syphilis	0.09% 1/1073 • 56 weeks 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.
Infections and infestations Periorbital cellulitis	0.09% 1/1073 • 56 weeks 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.
Infections and infestations Pneumonia	0.09% 1/1073 • 56 weeks 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.
Infections and infestations Wound sepsis	0.09% 1/1073 • 56 weeks 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.
Injury, poisoning and procedural complications Ankle fracture	0.09% 1/1073 • 56 weeks 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.
Injury, poisoning and procedural complications Intentional overdose	0.09% 1/1073 • 56 weeks 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.
Injury, poisoning and procedural complications Wrist fracture	0.09% 1/1073 • 56 weeks 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.
Metabolism and nutrition disorders Diabetes mellitus	0.09% 1/1073 • 56 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.19% 2/1073 • 56 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone cancer	0.09% 1/1073 • 56 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage I	0.09% 1/1073 • 56 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.09% 1/1073 • 56 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.09% 1/1073 • 56 weeks 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.
Nervous system disorders Cerebral infarction	0.09% 1/1073 • 56 weeks 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.
Nervous system disorders Complicated migraine	0.09% 1/1073 • 56 weeks 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.
Nervous system disorders Transient ischemic attack	0.09% 1/1073 • 56 weeks 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.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.09% 1/1073 • 56 weeks 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	0.28% 3/1073 • 56 weeks 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 Agitation	0.09% 1/1073 • 56 weeks 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 Anxiety	0.09% 1/1073 • 56 weeks 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 Suicidal ideation	0.09% 1/1073 • 56 weeks 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.09% 1/1073 • 56 weeks 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.
Vascular disorders Phlebitis	0.09% 1/1073 • 56 weeks 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

Measure	Vortioxetine n=1073 participants at risk Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks.
Gastrointestinal disorders Nausea	24.0% 258/1073 • 56 weeks 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.
Gastrointestinal disorders Diarrhea	7.5% 80/1073 • 56 weeks 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.
Gastrointestinal disorders Vomiting	6.3% 68/1073 • 56 weeks 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.
Gastrointestinal disorders Constipation	6.1% 65/1073 • 56 weeks 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.
Infections and infestations Nasopharyngitis	6.3% 68/1073 • 56 weeks 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.
Infections and infestations Viral upper respiratory tract infection	6.2% 66/1073 • 56 weeks 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.
Infections and infestations Upper respiratory tract infection	5.6% 60/1073 • 56 weeks 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.
Investigations Weight increased	6.1% 65/1073 • 56 weeks 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.
Nervous system disorders Headache	12.7% 136/1073 • 56 weeks 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.
Nervous system disorders Insomnia	5.2% 56/1073 • 56 weeks 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.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

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