Major Depressive Disorder
Conditions
Keywords
Depressive Disorder, Depression, Depressive Disorder, Major, Mood Disorders, Mental Disorders, Behavioural Symptoms
Brief summary
To evaluate the long-term safety and tolerability of flexible doses, 15 and 20 mg/day, of Vortioxetine over a period of 52 weeks in patients with Major Depressive Disorder (MDD)
Interventions
15 or 20 mg/day; tablets; orally
Sponsors
H. Lundbeck A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients who completed 8-week short-term treatment study, 13267A (NCT01140906), for Major Depressive Episode immediately prior to enrolment in this extension study
Exclusion criteria
* Any current psychiatric disorder other than MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV TR) * Female patients of childbearing potential who are not using effective contraception * Use of any psychoactive medication * The patient, in the investigator's clinical judgment, has a significant risk of suicide. Other protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With Adverse Events (AEs) | Baseline to end of the 4-week safety follow-up period |
| Percentage of Patients Who Withdrew Due to Intolerance to Treatment | Baseline to Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HAM-A Total Score After 52 Weeks of Treatment | Baseline and Week 52 | The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour 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 score from 0 to 56. The higher the score, the more severe. |
| Proportion of Responders at Week 52 (Response Defined as a >=50% Decrease in MADRS Total Score) | Baseline from lead-in study 13267A (NCT01140906) and Week 52 | — |
| Proportion of Remitters at Week 52 (Remission Defined as a MADRS Total Score <=10) | Baseline and Week 52 | — |
| Change From Baseline in MADRS Total Score After 52 Weeks of Treatment | Baseline and Week 52 | The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe. |
| ASEX Total Score After 52 Weeks of Treatment | Week 52 | The Arizona Sexual Experience Scale (ASEX) is a 5-item, patient selfrated scale that evaluates a patient's recent sexual experience. Patients are asked to assess their own experience over the last week (for example, How strong is your sex drive?, Are your orgasms satisfying?) and respond on a 6-point scale for each item. The ASEX is used to identify individuals with sexual dysfunction. Possible total score ranges from 5 to 30, with the higher score indicating more patient sexual dysfunction. |
| Risk of Suicidality Using C-SSRS Scores | Up to 52 weeks | The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by researchers at Columbia University as a tool to systematically assess suicidal ideation and behaviour in patients during participation in a clinical study. The C-SSRS is composed of questions that address suicidal behaviour and questions that address suicidal ideation, with subquestions that assess severity. The tool was administered via an interview with the patient. Different versions of the C-SSRS are available. In this study, the Since Last Visit Version was used at all visits. In order to assess the potential relationship between Vortioxetine and suicidality more accurately and systematically, C-SSRS data were collected during the Entire Study Period. |
| SDS Total Score After 52 Weeks of Treatment | Week 52 | The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe. |
| Change From Baseline in CGI-S Score After 52 Weeks of Treatment | Baseline and Week 52 | The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating. |
Participant flow
Recruitment details
Patients eligible to participate in Study 13267B were patients who had completed lead-in Study 13267A (NCT01140906) immediately prior to inclusion into present study, 13267B. The doses of Vortioxetine used in this long-term safety extension study were the same as those used in lead-in Study 13267A (NCT01140906).
Pre-assignment details
The study consisted of a 52-week open-label period and a 4-week Safety Follow-up Period.
Participants by arm
| Arm | Count |
|---|---|
| Vortioxetine 15 or 20 mg/Day | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative or Other Reasons | 8 |
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Non-compliance With Study Product | 3 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal of Consent | 1 |
Baseline characteristics
| Characteristic | Vortioxetine 15 or 20 mg/Day |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 12.7 |
| CGI-S: Baseline present study, 13267B | 3.0 units on a scale STANDARD_DEVIATION 1.3 |
| HAM-A: Baseline present study, 13267B | 11.9 units on a scale STANDARD_DEVIATION 6.6 |
| MADRS: Baseline from lead-in study 13267A (NCT01140906) | 31.1 units on a scale STANDARD_DEVIATION 3.3 |
| MADRS: Baseline present study, 13267B | 16.2 units on a scale STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 71 |
| serious Total, serious adverse events | 1 / 71 |
Outcome results
Primary
Number of Patients With Adverse Events (AEs)
Time frame: Baseline to end of the 4-week safety follow-up period
Population: all-patients-treated set (APTS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Number of Patients With Adverse Events (AEs) | Patients With AEs | 56 participants |
| Vortioxetine 15 or 20 mg/Day | Number of Patients With Adverse Events (AEs) | Patients With Serious AEs (SAEs) | 1 participants |
| Vortioxetine 15 or 20 mg/Day | Number of Patients With Adverse Events (AEs) | Patients With AEs Leading to Withdrawal | 7 participants |
Primary
Percentage of Patients Who Withdrew Due to Intolerance to Treatment
Time frame: Baseline to Week 52
Population: APTS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Percentage of Patients Who Withdrew Due to Intolerance to Treatment | 9.9 percentage of patients |
Secondary
ASEX Total Score After 52 Weeks of Treatment
The Arizona Sexual Experience Scale (ASEX) is a 5-item, patient selfrated scale that evaluates a patient's recent sexual experience. Patients are asked to assess their own experience over the last week (for example, How strong is your sex drive?, Are your orgasms satisfying?) and respond on a 6-point scale for each item. The ASEX is used to identify individuals with sexual dysfunction. Possible total score ranges from 5 to 30, with the higher score indicating more patient sexual dysfunction.
Time frame: Week 52
Population: APTS, OC
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | ASEX Total Score After 52 Weeks of Treatment | 18.60 units on a scale | Standard Error 0.96 |
Secondary
Change From Baseline in CGI-S Score After 52 Weeks of Treatment
The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.
Time frame: Baseline and Week 52
Population: FAS, OC
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Change From Baseline in CGI-S Score After 52 Weeks of Treatment | -1.49 units on a scale | Standard Deviation 1.46 |
Secondary
Change From Baseline in HAM-A Total Score After 52 Weeks of Treatment
The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour 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 score from 0 to 56. The higher the score, the more severe.
Time frame: Baseline and Week 52
Population: FAS, OC
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Change From Baseline in HAM-A Total Score After 52 Weeks of Treatment | -7.85 units on a scale | Standard Deviation 7.49 |
Secondary
Change From Baseline in MADRS Total Score After 52 Weeks of Treatment
The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.
Time frame: Baseline and Week 52
Population: full-analysis set (FAS), observed cases (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Change From Baseline in MADRS Total Score After 52 Weeks of Treatment | -10.9 units on a scale | Standard Deviation 9.99 |
Secondary
Proportion of Remitters at Week 52 (Remission Defined as a MADRS Total Score <=10)
Time frame: Baseline and Week 52
Population: FAS, OC
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Proportion of Remitters at Week 52 (Remission Defined as a MADRS Total Score <=10) | 80.9 percentage of patients |
Secondary
Proportion of Responders at Week 52 (Response Defined as a >=50% Decrease in MADRS Total Score)
Time frame: Baseline from lead-in study 13267A (NCT01140906) and Week 52
Population: FAS, OC
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Proportion of Responders at Week 52 (Response Defined as a >=50% Decrease in MADRS Total Score) | 93.6 percentage of patients |
Secondary
Risk of Suicidality Using C-SSRS Scores
The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by researchers at Columbia University as a tool to systematically assess suicidal ideation and behaviour in patients during participation in a clinical study. The C-SSRS is composed of questions that address suicidal behaviour and questions that address suicidal ideation, with subquestions that assess severity. The tool was administered via an interview with the patient. Different versions of the C-SSRS are available. In this study, the Since Last Visit Version was used at all visits. In order to assess the potential relationship between Vortioxetine and suicidality more accurately and systematically, C-SSRS data were collected during the Entire Study Period.
Time frame: Up to 52 weeks
Population: Suicidal Ideation and Behaviour Based on C-SSRS Scores by Columbia Classification Algorithm for Suicide Assessment (C-CASA) - APTS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | Suicidal Ideation | 4 participants |
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | No suicidal ideation or behaviour | 67 participants |
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | Any non-suicidal self-injurious behavior | 0 participants |
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | Preparatory action towards imminent suicidal behav | 0 participants |
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | Not fatal suicide attempt | 0 participants |
| Vortioxetine 15 or 20 mg/Day | Risk of Suicidality Using C-SSRS Scores | Completed suicide | 0 participants |
Secondary
SDS Total Score After 52 Weeks of Treatment
The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe.
Time frame: Week 52
Population: FAS, OC
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | SDS Total Score After 52 Weeks of Treatment | 4.85 units on a scale | Standard Deviation 5.84 |