Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Depression, Melancholia, Mood Disorder, Dysthymic Disorder, Drug Therapy
Brief summary
The purpose of this study is to determine the long-term efficacy and safety of vortioxetine, once daily (QD), in adults with major depressive disorder.
Detailed description
The drug that was tested in this study is called vortioxetine. Vortioxetine is being tested to treat depression in people who have major depressive disorder (MDD). This study looked at MDD relief in people who took vortioxetine. The study enrolled 836 patients that had completed one of two other vortioxetine studies. Participants received 5 mg of vortioxetine for the first week of treatment. After completing the first week of treatment, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day based on participant's response as judged by the doctor. All participants were asked to take one encapsulated tablet at the same time each day throughout the study. This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 56 weeks. Participants made 13 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.
Interventions
DRUGVortioxetine
Encapsulated vortioxetine immediate-release tablets
Sponsors
H. Lundbeck A/S
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Has completed the double blind treatment period of either study Lu AA21004\_304 (NCT00672620) or LuAA21004\_305 (NCT00735709) immediately prior to enrollment in the extension study (ie, the baseline visit is the same visit as the completion visit of the double blind treatment of the preceding protocol). * Suffers from a major depressive episode as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.xx) at entry into the prior Lu AA21004\_304 or Lu AA21004\_305 study.
Exclusion criteria
* In addition to meeting the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physical Examination Findings | Baseline and Week 52 | Physical examination consisted of the following body systems: (1) appearance; (2) extremities; (3) skin; (4) head and neck; (5) eyes, ears, nose, and throat; (6) lungs and chest; (7) heart and cardiovascular system; (8) abdomen; and (9) musculoskeletal system. An assessment of the nervous system was conducted; any findings were captured under the appropriate body area. Each system was assessed as normal or abnormal. |
| Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Weeks 4, 8, 12, 20, 28, 36, 44 and 52 | Participants with at least one post-baseline potentially clinically significant (as defined in the table below) serum chemistry, hematology or urinalysis result. ULN = upper limit of normal; LLN = Lower limit of normal. |
| Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Weeks 4, 12, 24, 36 and 52 | A standard 12-lead ECG was performed at the designated study visits. The central reader reviewed and recorded the intervals (PR, QRS, RR, QT, and corrected QT interval \[QTc\]), and interpreted the ECG using 1 of the following categories: within normal limits or abnormal. The number of participants with at least one post-baseline potentially clinically significant ECG finding is reported. bpm = beats per minute; QTcB = QT interval corrected using Bazett's formula; QTcF = QT interval corrected using Fridericia's formula. |
| Number of Participants With Adverse Events (AEs) | From the first dose of open-label study drug until 4 weeks after the last dose (up to 56 weeks) | The intensity (severity) of each AE was defined as: * Mild: caused minimal discomfort and did not interfere in a significant manner with normal activities. * Moderate: sufficiently uncomfortable to produce some impairment of normal activities. * Severe: incapacitating, preventing the patient from participating in normal activities. The causal relationship between an AE and study drug was assessed by the investigator as Probable, Possible or Not Related; Related=AEs with causality of Possibly or Probably. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect, or was an important medical event that either jeopardized the patient, required intervention to prevent any of the SAEs defined above, a suicide attempt or an abortion. |
| Number of Participants With Potentially Clinically Significant Vital Sign Findings | Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 | Participants with at least one potentially clinically significant post-baseline vital sign finding. The definition of clinically significant is included in the table below for each parameter. SSBP = supine systolic blood pressure; SDBP = supine diastolic blood pressure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the Final Visit in the Sheehan Disability Scale | Baseline and Week 52 | The Sheehan Disability Scale (SDS) 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. |
| Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52. | The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks. |
| Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline and Week 52 | Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks. |
| Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Baseline and Weeks 4, 24 and 52 | 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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks. |
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Baseline and Weeks 4, 24 and 52 | The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks. |
| Change From Baseline in the Clinical Global Impression of Severity of Illness Scale | Baseline and Weeks 4, 24 and 52 | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks. |
| Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Baseline and Week 52 | The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst). |
Countries
Australia, Croatia, France, Germany, Latvia, Lithuania, Malaysia, Netherlands, Poland, Russia, Serbia, South Africa, South Korea, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 88 investigative sites in Australia, Croatia, France, Germany, Korea, Latvia, Lithuania, Malaysia, The Netherlands, Poland, Russia, Taiwan, Ukraine, and the United States from 17 June 2008 to 23 August 2010.
Pre-assignment details
Participants who completed short-term efficacy and safety studies Lu AA21004\_304 (NCT00672620) and LuAA21004\_305 (NCT00735709) were eligible to receive the 52-week treatment with vortioxetine in this open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Vortioxetine Vortioxetine 2.5 mg, 5 mg or 10 mg, encapsulated tablets, orally, once daily for up to 52 weeks. For the first week of treatment all participants received 5 mg/day vortioxetine, thereafter, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day, based on participant's response and tolerability as judged by the investigator. | 836 |
| Total | 836 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 49 |
| Overall Study | Lack of Efficacy | 35 |
| Overall Study | Lost to Follow-up | 59 |
| Overall Study | Non-Compliance with Study Drug | 28 |
| Overall Study | Other | 39 |
| Overall Study | Protocol Deviations | 19 |
| Overall Study | Withdrawal of Consent | 81 |
Baseline characteristics
| Characteristic | Vortioxetine |
|---|---|
| 24-item Hamilton Depression Scale total score | 17.6 scores on a scale STANDARD_DEVIATION 9.4 |
| Age Continuous | 45.5 Years STANDARD_DEVIATION 12.78 |
| Age, Customized ≤55 years | 636 Participants |
| Age, Customized >55 years | 200 Participants |
| Body Mass Index (BMI) | 28.41 kg/m^2 STANDARD_DEVIATION 7.074 |
| Clinical Global Impression - Severity scale score | 3.2 scores on a scale STANDARD_DEVIATION 1.26 |
| Hamilton Anxiety Scale total score | 12.1 scores on a scale STANDARD_DEVIATION 7.17 |
| Height | 169.00 cm STANDARD_DEVIATION 9.777 |
| Montgomery Åsberg Depression Rating Scale (MADRS) total score | 16.6 scores on a scale STANDARD_DEVIATION 9.24 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 54 Participants |
| Race/Ethnicity, Customized Black | 86 Participants |
| Race/Ethnicity, Customized Caucasian (White, including Hispanic) | 693 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 53 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian/ Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic/Non-Latino | 782 Participants |
| Region of Enrollment Australia | 4 Participants |
| Region of Enrollment Croatia | 11 Participants |
| Region of Enrollment France | 11 Participants |
| Region of Enrollment Germany | 207 Participants |
| Region of Enrollment Latvia | 20 Participants |
| Region of Enrollment Lithuania | 10 Participants |
| Region of Enrollment Malaysia | 17 Participants |
| Region of Enrollment Netherlands | 7 Participants |
| Region of Enrollment Poland | 57 Participants |
| Region of Enrollment Republic of Korea | 25 Participants |
| Region of Enrollment Russia | 40 Participants |
| Region of Enrollment Taiwan | 3 Participants |
| Region of Enrollment Ukraine | 37 Participants |
| Region of Enrollment United States | 387 Participants |
| Sex: Female, Male Female | 526 Participants |
| Sex: Female, Male Male | 310 Participants |
| Weight | 81.16 kg STANDARD_DEVIATION 20.829 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 452 / 834 |
| serious Total, serious adverse events | 29 / 834 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
The intensity (severity) of each AE was defined as: * Mild: caused minimal discomfort and did not interfere in a significant manner with normal activities. * Moderate: sufficiently uncomfortable to produce some impairment of normal activities. * Severe: incapacitating, preventing the patient from participating in normal activities. The causal relationship between an AE and study drug was assessed by the investigator as Probable, Possible or Not Related; Related=AEs with causality of Possibly or Probably. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect, or was an important medical event that either jeopardized the patient, required intervention to prevent any of the SAEs defined above, a suicide attempt or an abortion.
Time frame: From the first dose of open-label study drug until 4 weeks after the last dose (up to 56 weeks)
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Any adverse event | 589 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Related adverse event | 413 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Not related adverse event | 176 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Mild adverse event | 187 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Moderate adverse event | 320 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Severe adverse event | 82 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Adverse event leading to early termination | 50 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Serious adverse event | 29 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Serious related adverse event | 5 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Serious not related adverse event | 33 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Serious adverse event leading to early termination | 11 participants |
| Vortioxetine | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
Primary
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed at the designated study visits. The central reader reviewed and recorded the intervals (PR, QRS, RR, QT, and corrected QT interval \[QTc\]), and interpreted the ECG using 1 of the following categories: within normal limits or abnormal. The number of participants with at least one post-baseline potentially clinically significant ECG finding is reported. bpm = beats per minute; QTcB = QT interval corrected using Bazett's formula; QTcF = QT interval corrected using Fridericia's formula.
Time frame: Weeks 4, 12, 24, 36 and 52
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Heart rate ≤50 bpm and change ≤-15bpm | 9 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Heart rate ≥120 bpm and change ≥15 bpm | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | RR interval <500 msec and change ≤-200 msec | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | RR interval >1200 msec and change ≥200 msec | 13 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | PR interval <120 msec | 31 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | PR interval ≥250 msec | 2 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QT interval <280 msec | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QT interval >500 msec | 2 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcB <340 msec | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcB >500 msec | 3 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcB Change <-60 msec | 6 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF <340 msec | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF >500 msec | 2 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Change <-60 msec | 3 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Change >60 msec | 2 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcB Change >60 msec | 4 participants |
Primary
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Participants with at least one post-baseline potentially clinically significant (as defined in the table below) serum chemistry, hematology or urinalysis result. ULN = upper limit of normal; LLN = Lower limit of normal.
Time frame: Weeks 4, 8, 12, 20, 28, 36, 44 and 52
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Alanine aminotransferase (ALT) ≥ 3 X ULN | 3 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Aspartate aminotransferase (AST) ≥ 3 X ULN | 6 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Bilirubin ≥ 34.2 μmol/L | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Cholesterol ≥ 7.8 mmol/L | 49 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Creatine kinase ≥ 2 X ULN | 80 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Creatinine ≥ 175 μmol/L | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Glucose ≤ 2.8 mmol/L | 9 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Glucose ≥ 13.9 mmol/L | 7 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | High density lipoprotein cholesterol < 0.9 mmol/L | 102 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Low density lipoprotein cholesterol ≥ 5.0 mmol/L | 69 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Potassium ≤ 3.0 mmol/L | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Potassium ≥ 5.5 mmol/L | 45 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Sodium ≤ 125 mmol/L | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Sodium ≥ 155 mmol/L | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Triglycerides ≥ 3.40 mmol/L | 168 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Urate ≤ 0.7 X LLN | 4 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Urate ≥ 1.3 XULN | 12 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Eosinophils ≥ 0.6 10^9/L | 24 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Erythrocytes ≤ 0.9 X LLN | 9 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Erythrocytes ≥ 1.1 X ULN | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Hematocrit ≤ 0.9 X LLN | 16 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Hemoglobin ≤ 0.9 X LLN | 41 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Leukocytes ≤ 2.8 X 10^9/L | 10 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Leukocytes ≥ 16 X 10^9/L | 3 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Lymphocytes ≤ 0.6 X 10^9/L | 5 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Lymphocytes ≥ 7 X 10^9/L | 0 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Neutrophils ≤ 1.4 X 10^9/L | 26 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Neutrophils ≥ 15 X 10^9/L | 2 participants |
Primary
Number of Participants With Potentially Clinically Significant Vital Sign Findings
Participants with at least one potentially clinically significant post-baseline vital sign finding. The definition of clinically significant is included in the table below for each parameter. SSBP = supine systolic blood pressure; SDBP = supine diastolic blood pressure.
Time frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | SSBP ≤90 mmHg and decrease of ≥20 mmHg | 7 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | SSBP ≥180 mmHg and increase of ≥20 mmHg | 4 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | SDBP ≤50 mmHg and decrease of ≥15 mmHg | 1 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | SDBP ≥105 mmHg and increase of ≥15 mmHg | 8 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | Supine pulse rate ≤50 bpm and decrease of ≥15 bpm | 7 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | Supine pulse rate ≥120 bpm and increase of ≥15 bpm | 2 participants |
| Vortioxetine | Number of Participants With Potentially Clinically Significant Vital Sign Findings | Weight Change of ≥7% weight | 155 participants |
Primary
Physical Examination Findings
Physical examination consisted of the following body systems: (1) appearance; (2) extremities; (3) skin; (4) head and neck; (5) eyes, ears, nose, and throat; (6) lungs and chest; (7) heart and cardiovascular system; (8) abdomen; and (9) musculoskeletal system. An assessment of the nervous system was conducted; any findings were captured under the appropriate body area. Each system was assessed as normal or abnormal.
Time frame: Baseline and Week 52
Population: The safety set included all participants who enrolled and received at least 1 dose of open-label study medication. Results include data for participants with available data at each time point; 834 participants at Baseline and 524 participants at Week 52.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Physical Examination Findings | Appearance at Baseline: Normal | 758 participants |
| Vortioxetine | Physical Examination Findings | Appearance at Baseline: Abnormal | 76 participants |
| Vortioxetine | Physical Examination Findings | Appearance at Week 52: Normal | 484 participants |
| Vortioxetine | Physical Examination Findings | Appearance at Week 52: Abnormal | 40 participants |
| Vortioxetine | Physical Examination Findings | Extremities at Baseline: Normal | 806 participants |
| Vortioxetine | Physical Examination Findings | Extremities at Baseline: Abnormal | 28 participants |
| Vortioxetine | Physical Examination Findings | Extremities at Week 52: Normal | 511 participants |
| Vortioxetine | Physical Examination Findings | Extremities at Week 52: Abnormal | 13 participants |
| Vortioxetine | Physical Examination Findings | Skin at Baseline: Normal | 730 participants |
| Vortioxetine | Physical Examination Findings | Skin at Baseline: Abnormal | 104 participants |
| Vortioxetine | Physical Examination Findings | Skin at Week 52: Normal | 465 participants |
| Vortioxetine | Physical Examination Findings | Skin at Week 52: Abnormal | 59 participants |
| Vortioxetine | Physical Examination Findings | Head-Neck at Baseline: Normal | 822 participants |
| Vortioxetine | Physical Examination Findings | Head-Neck at Baseline: Abnormal | 12 participants |
| Vortioxetine | Physical Examination Findings | Head-Neck at Week 52: Normal | 518 participants |
| Vortioxetine | Physical Examination Findings | Head-Neck at Week 52: Abnormal | 6 participants |
| Vortioxetine | Physical Examination Findings | Eyes-Ears-Nose-Throat at Baseline: Normal | 772 participants |
| Vortioxetine | Physical Examination Findings | Eyes-Ears-Nose-Throat at Baseline: Abnormal | 62 participants |
| Vortioxetine | Physical Examination Findings | Eyes-Ears-Nose-Throat at Week 52: Normal | 485 participants |
| Vortioxetine | Physical Examination Findings | Eyes-Ears-Nose-Throat at Week 52: Abnormal | 39 participants |
| Vortioxetine | Physical Examination Findings | Lungs-Chest at Baseline: Normal | 827 participants |
| Vortioxetine | Physical Examination Findings | Lungs-Chest at Baseline: Abnormal | 7 participants |
| Vortioxetine | Physical Examination Findings | Lungs-Chest at Week 52: Normal | 523 participants |
| Vortioxetine | Physical Examination Findings | Lungs-Chest at Week 52: Abnormal | 1 participants |
| Vortioxetine | Physical Examination Findings | Heart/Cardiovascular at Baseline: Normal | 816 participants |
| Vortioxetine | Physical Examination Findings | Heart/Cardiovascular at Baseline: Abnormal | 18 participants |
| Vortioxetine | Physical Examination Findings | Heart/Cardiovascular at Week 52: Normal | 512 participants |
| Vortioxetine | Physical Examination Findings | Heart/Cardiovascular at Week 52: Abnormal | 12 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Baseline: Normal | 818 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Baseline: Abnormal | 12 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Baseline: Not done | 4 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Week 52: Normal | 515 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Week 52: Abnormal | 8 participants |
| Vortioxetine | Physical Examination Findings | Abdomen at Week 52: Not done | 1 participants |
| Vortioxetine | Physical Examination Findings | Musculoskeletal at Baseline: Normal | 790 participants |
| Vortioxetine | Physical Examination Findings | Musculoskeletal at Baseline: Abnormal | 44 participants |
| Vortioxetine | Physical Examination Findings | Musculoskeletal at Week 52: Normal | 493 participants |
| Vortioxetine | Physical Examination Findings | Musculoskeletal at Week 52: Abnormal | 31 participants |
Secondary
Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52.
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available data. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 1 (n=805) | -1.1 scores on a scale | Standard Deviation 5.27 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 2 (n=822) | -3.1 scores on a scale | Standard Deviation 6.1 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 4 (n=805) | -4.7 scores on a scale | Standard Deviation 7.07 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 8 (n=752) | -6.5 scores on a scale | Standard Deviation 7.43 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 12 (n=715) | -7.0 scores on a scale | Standard Deviation 8.27 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 16 (n=671) | -7.7 scores on a scale | Standard Deviation 8.45 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 20 (n=639) | -8.4 scores on a scale | Standard Deviation 8.51 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 24 (n=613) | -8.3 scores on a scale | Standard Deviation 8.92 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 28 (n=599) | -8.9 scores on a scale | Standard Deviation 8.91 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 36 (n=568) | -9.3 scores on a scale | Standard Deviation 9.05 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 44 (n=540) | -9.6 scores on a scale | Standard Deviation 9.32 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Week 52 (n=522) | -10.0 scores on a scale | Standard Deviation 8.86 |
| Vortioxetine | Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score | Final Visit (n=829) | -7.9 scores on a scale | Standard Deviation 9.66 |
Secondary
Change From Baseline in the Clinical Global Impression of Severity of Illness Scale
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time frame: Baseline and Weeks 4, 24 and 52
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available data. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline in the Clinical Global Impression of Severity of Illness Scale | Week 4 (n=818) | -0.53 scores on a scale | Standard Deviation 1.002 |
| Vortioxetine | Change From Baseline in the Clinical Global Impression of Severity of Illness Scale | Week 24 (n=642) | -0.98 scores on a scale | Standard Deviation 1.295 |
| Vortioxetine | Change From Baseline in the Clinical Global Impression of Severity of Illness Scale | Week 52 (n= 527) | -1.33 scores on a scale | Standard Deviation 1.266 |
| Vortioxetine | Change From Baseline in the Clinical Global Impression of Severity of Illness Scale | Final Visit (n=818) | -1.00 scores on a scale | Standard Deviation 1.338 |
Secondary
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time frame: Baseline and Weeks 4, 24 and 52
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available data. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 4 (n=818) | -2.9 scores on a scale | Standard Deviation 5.12 |
| Vortioxetine | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 24 (n=642) | -5.1 scores on a scale | Standard Deviation 6.44 |
| Vortioxetine | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 52 (n=527) | -6.6 scores on a scale | Standard Deviation 6.38 |
| Vortioxetine | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Final Visit (n= 818) | -5.2 scores on a scale | Standard Deviation 6.76 |
Secondary
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time frame: Baseline and Weeks 4, 24 and 52
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available data. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=818) | -4.5 scores on a scale | Standard Deviation 7.38 |
| Vortioxetine | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 24 (n=642) | -7.9 scores on a scale | Standard Deviation 9.24 |
| Vortioxetine | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 52 (n=526) | -9.5 scores on a scale | Standard Deviation 8.9 |
| Vortioxetine | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Final Visit (n=818) | -7.4 scores on a scale | Standard Deviation 9.81 |
Secondary
Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36)
The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst).
Time frame: Baseline and Week 52
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available Final Visit data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Physical functioning subscore (n=824) | 4.5 scores on a scale | Standard Deviation 15.88 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Role-physical subscore (n=824) | 8.1 scores on a scale | Standard Deviation 25.51 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Bodily pain subscore (n=824) | 4.9 scores on a scale | Standard Deviation 24.29 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | General health subscore (n=823) | 6.4 scores on a scale | Standard Deviation 18.38 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Vitality subscore (n=824) | 10.1 scores on a scale | Standard Deviation 23.03 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Social functioning subscore (n=824) | 10.9 scores on a scale | Standard Deviation 26.9 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Role-emotional subscore (n=824) | 12.3 scores on a scale | Standard Deviation 28.24 |
| Vortioxetine | Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36) | Mental health subscore (n=824) | 10.7 scores on a scale | Standard Deviation 22.04 |
Secondary
Change From Baseline to the Final Visit in the Sheehan Disability Scale
The Sheehan Disability Scale (SDS) 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.
Time frame: Baseline and Week 52
Population: Participants in the safety analysis set who had at least 1 post-baseline efficacy measurement, and with available Final Visit data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | Change From Baseline to the Final Visit in the Sheehan Disability Scale | -4.6 scores on a scale | Standard Deviation 8.01 |
Secondary
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire
Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.
Time frame: Baseline and Week 52
Population: Safety set with available data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 137 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 4 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to depression | 0 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 53 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to depression | 42 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 52: Any resource use | 138 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 52:Any hospitalization-related services | 7 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Final Visit: Hospitalization related to depression | 0 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 52: Any sick leave | 41 participants |
| Vortioxetine | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 52: Sick leave related to depression | 25 participants |