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

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ClinicalTrials.gov Identifier: NCT01152996
Recruitment Status : Completed
First Posted : June 29, 2010
Results First Posted : May 28, 2014
Last Update Posted : May 28, 2014
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Depressive Disorder, Major
Intervention Drug: Vortioxetine
Enrollment 1075

Recruitment Details Participants took part in the study at 143 investigative sites in the United States from 07 Sep 2010 to 31 May 2013.
Pre-assignment Details 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.
Arm/Group Title Vortioxetine
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 1075
Treated 1073
Completed 538
Not Completed 537
Reason Not Completed
Withdrawal by Subject             142
Adverse Event             115
Lost to Follow-up             112
Lack of Efficacy             68
Noncompliance             41
Other             36
Protocol Violation             22
Elevated liver enzymes             1
Arm/Group Title Vortioxetine
Hide Arm/Group Description 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 Number of Baseline Participants 1075
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1075 participants
44.5  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1075 participants
Female
790
  73.5%
Male
285
  26.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1075 participants
Caucasian (or White, including Hispanic) 813
Black/African American 249
Asian 7
American Indian/Alaska Native 5
Native Hawaiian/Other Pacific Islander 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1075 participants
Hispanic or Latino 104
Non-Hispanic and Non-Latino 971
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg)
Number Analyzed 1075 participants
88.77  (24.160)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 1075 participants
31.60  (8.061)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 1075 participants
167.44  (9.456)
Montgomery Åsberg Depression Rating Scale (MADRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 1075 participants
20.0  (10.70)
[1]
Measure Description: 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.
Hamilton Anxiety Scale (HAM-A) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 1075 participants
11.6  (6.65)
[1]
Measure Description: 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.
Clinical Global Impression - Severity scale (CGI-S) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 1075 participants
3.3  (1.21)
[1]
Measure Description: 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). Higher scores indicate greater severity of illness.
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5%
Hide Description 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.
Time Frame Over the 52 week period
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Hide Analysis Population Description
Safety set
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1073
Measure Type: Number
Unit of Measure: participants
Nausea 258
Diarrhea 80
Vomiting 68
Constipation 65
Nasopharyngitis 68
Viral upper respiratory tract infection 66
Upper respiratory tract infection 60
Weight increased 65
Headache 136
Insomnia 56
2.Primary Outcome
Title Number of Participants With Serious Treatment-Emergent Adverse Events
Hide Description 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.
Time Frame Over the 52 week period
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Hide Analysis Population Description
Safety set
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1073
Measure Type: Number
Unit of Measure: participants
29
3.Primary Outcome
Title Treatment-Emergent Adverse Events Leading to Study Discontinuation
Hide Description 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.
Time Frame Over the 52 week period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1073
Measure Type: Number
Unit of Measure: participants
117
4.Secondary Outcome
Title Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description 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.
Time Frame Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1043
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 1 (n=1043) -2.7  (6.32)
Week 2 (n=1043) -4.8  (7.50)
Week 4 (n=1004) -6.1  (8.50)
Week 8 (n=936) -7.9  (9.19)
Week 12 (n=843) -8.5  (9.55)
Week 16 (n=777) -9.1  (9.50)
Week 20 (n=747) -9.4  (10.03)
Week 24 (n=697) -9.7  (9.64)
Week 28 (n=670) -9.5  (10.20)
Week 36 (n=617) -9.7  (10.44)
Week 44 (n=573) -10.3  (10.70)
Week 52 (n=534) -10.3  (11.00)
5.Secondary Outcome
Title Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
Hide Description 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.
Time Frame Baseline and Weeks 4, 24, and 52
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Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1029
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 (n=1029) -2.6  (4.98)
Week 24 (n=742) -4.2  (5.84)
Week 52 (n=548) -4.8  (6.52)
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S)
Hide Description 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.
Time Frame Baseline and Weeks 4, 24, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 1030
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 (n=1030) -0.6  (0.99)
Week 24 (n=743) -1.0  (1.16)
Week 52 (n=549) -1.2  (1.32)
7.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score
Hide Description 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.
Time Frame Baseline and Weeks 12, 24, 36, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 650
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 (n=650) -2.8  (6.69)
Week 24 (n=494) -3.9  (6.88)
Week 36 (n=414) -4.0  (7.37)
Week 52 (n=381) -4.7  (7.11)
8.Secondary Outcome
Title Change From Baseline in SDS Work/School Subscale
Hide Description 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.
Time Frame Baseline and Weeks 12, 24, 36, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 650
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 (n=650) -0.8  (2.42)
Week 24 (n=494) -1.2  (2.48)
Week 36 (n=414) -1.2  (2.60)
Week 52 (n=381) -1.4  (2.61)
9.Secondary Outcome
Title Change From Baseline in SDS Social Life Subscale
Hide Description 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.
Time Frame Baseline and Weeks 12, 24, 36, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 942
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 (n=942) -1.0  (2.53)
Week 24 (n=721) -1.4  (2.55)
Week 36 (n=617) -1.4  (2.82)
Week 52 (n=545) -1.6  (2.85)
10.Secondary Outcome
Title Change From Baseline in SDS Family Life/Home Responsibilities Subscale
Hide Description 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.
Time Frame Baseline and Weeks 12, 24, 36, and 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set, observed cases (OC)
Arm/Group Title Vortioxetine
Hide Arm/Group Description:
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 Number of Participants Analyzed 942
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 (n=942) -0.9  (2.39)
Week 24 (n=721) -1.3  (2.47)
Week 36 (n=617) -1.4  (2.74)
Week 52 (n=545) -1.6  (2.76)
Time Frame 56 weeks
Adverse Event Reporting Description 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.
 
Arm/Group Title Vortioxetine
Hide Arm/Group Description 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.
All-Cause Mortality
Vortioxetine
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vortioxetine
Affected / at Risk (%)
Total   29/1073 (2.70%) 
Cardiac disorders   
Atrial fibrillation  1  1/1073 (0.09%) 
Gastrointestinal disorders   
Abdominal pain  1  1/1073 (0.09%) 
Esophageal rupture  1  1/1073 (0.09%) 
Hepatobiliary disorders   
Cholecystitis acute  1  2/1073 (0.19%) 
Cholecystitis  1  1/1073 (0.09%) 
Cholelithiasis  1  1/1073 (0.09%) 
Infections and infestations   
Anal abscess  1  1/1073 (0.09%) 
Latent syphilis  1  1/1073 (0.09%) 
Periorbital cellulitis  1  1/1073 (0.09%) 
Pneumonia  1  1/1073 (0.09%) 
Wound sepsis  1  1/1073 (0.09%) 
Injury, poisoning and procedural complications   
Ankle fracture  1  1/1073 (0.09%) 
Intentional overdose  1  1/1073 (0.09%) 
Wrist fracture  1  1/1073 (0.09%) 
Metabolism and nutrition disorders   
Diabetes mellitus  1  1/1073 (0.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer female  1  2/1073 (0.19%) 
Bone cancer  1  1/1073 (0.09%) 
Breast cancer stage I  1  1/1073 (0.09%) 
Malignant melanoma  1  1/1073 (0.09%) 
Uterine leiomyoma  1  1/1073 (0.09%) 
Nervous system disorders   
Cerebral infarction  1  1/1073 (0.09%) 
Complicated migraine  1  1/1073 (0.09%) 
Transient ischemic attack  1  1/1073 (0.09%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/1073 (0.09%) 
Psychiatric disorders   
Suicide attempt  1  3/1073 (0.28%) 
Agitation  1  1/1073 (0.09%) 
Anxiety  1  1/1073 (0.09%) 
Suicidal ideation  1  1/1073 (0.09%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/1073 (0.09%) 
Vascular disorders   
Phlebitis  1  1/1073 (0.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vortioxetine
Affected / at Risk (%)
Total   854/1073 (79.59%) 
Gastrointestinal disorders   
Nausea  1  258/1073 (24.04%) 
Diarrhea  1  80/1073 (7.46%) 
Vomiting  1  68/1073 (6.34%) 
Constipation  1  65/1073 (6.06%) 
Infections and infestations   
Nasopharyngitis  1  68/1073 (6.34%) 
Viral upper respiratory tract infection  1  66/1073 (6.15%) 
Upper respiratory tract infection  1  60/1073 (5.59%) 
Investigations   
Weight increased  1  65/1073 (6.06%) 
Nervous system disorders   
Headache  1  136/1073 (12.67%) 
Insomnia  1  56/1073 (5.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The 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.
Results Point of Contact
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01152996     History of Changes
Other Study ID Numbers: LuAA21004_314
U1111-1115-4927 ( Registry Identifier: WHO )
First Submitted: June 28, 2010
First Posted: June 29, 2010
Results First Submitted: April 29, 2014
Results First Posted: May 28, 2014
Last Update Posted: May 28, 2014