Depressive Disorder, Major
Conditions
Brief summary
This study will evaluate the safety and efficacy of onabotulinumtoxinA (BOTOX®) compared with placebo as treatment for major depressive disorder (MDD) in adult females.
Interventions
BIOLOGICALonabotulinumtoxinA
OnabotulinumtoxinA injected into protocol-specified areas on Day 1.
DRUGNormal Saline
Placebo (normal saline) injected into protocol-specified areas on Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Moderate to severe major depressive disorder
Exclusion criteria
* Prior treatment with botulinum toxin of any serotype for any reason * Use of antidepressant medication for depression within 2 weeks of study * Diagnosis of Myasthenia gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | The MADRS is a 10-item scale completed by clinic personnel that assesses the subject's symptoms of depression. Each question is answered on a 7-point scale ranging from no symptoms to worst possible symptoms. The total score is summed for all responses and ranges from 0 to 60. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
| Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 6 | The MADRS is a 10-item scale completed by clinic personnel that assesses the subject's symptoms of depression. Each question is answered on a 7-point scale ranging from no symptoms to worst possible symptoms. The total score is summed for all responses and ranges from 0 to 60. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | Baseline | The CGI-S is a 7-point scale assessed by the clinician to rate the severity of the subject's symptoms. Scores range from 1 to 7, from normal (1, not at all ill) to among the most extremely ill patients (7). A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
| Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | 24 Weeks | The CGI-S is a 7-point scale assessed by the clinician to rate the severity of the subject's symptoms. Scores range from 1 to 7, from normal (1, not at all ill) to among the most extremely ill patients (7). A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
| Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | Baseline | The HAM-D17 is assessed by the clinician based on subject interview. The total scores range from 0 to 53. A higher total score indicates more severe depression. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
| Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | 24 Weeks | The HAM-D17 is assessed by the clinician based on subject interview. The total scores range from 0 to 53. A higher total score indicates more severe depression. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U Placebo (normal saline) for onabotulinumtoxinA 50 U injected into protocol-specified areas on Day 1. | 67 |
| onabotulinumtoxinA 50 U OnabotulinumtoxinA 50 U injected into protocol-specified areas on Day 1. | 65 |
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U Placebo (normal saline) for onabotulinumtoxinA 30 U injected into protocol-specified areas on Day 1. | 58 |
| onabotulinumtoxinA 30 U OnabotulinumtoxinA 30 U injected into protocol-specified areas on Day 1. | 65 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 3 |
| Overall Study | Investigator Decision - Relapse | 9 | 7 | 8 | 5 |
| Overall Study | Lack of Efficacy | 5 | 7 | 4 | 3 |
| Overall Study | Lost to Follow-up | 4 | 5 | 7 | 5 |
| Overall Study | Other Reasons | 3 | 3 | 3 | 3 |
| Overall Study | Personal Reasons | 6 | 6 | 4 | 9 |
| Overall Study | Physician Decision | 2 | 3 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo (Normal Saline) for onabotulinumtoxinA 50 U | onabotulinumtoxinA 50 U | Placebo (Normal Saline) for onabotulinumtoxinA 30 U | onabotulinumtoxinA 30 U | Total |
|---|---|---|---|---|---|
| Age, Customized <40 years | 26 Participants | 21 Participants | 21 Participants | 26 Participants | 94 Participants |
| Age, Customized ≥ 40 years | 41 Participants | 44 Participants | 37 Participants | 39 Participants | 161 Participants |
| Sex: Female, Male Female | 67 Participants | 65 Participants | 58 Participants | 65 Participants | 255 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 67 | 18 / 65 | 10 / 58 | 21 / 65 |
| serious Total, serious adverse events | 5 / 67 | 0 / 65 | 1 / 58 | 3 / 65 |
Outcome results
Primary
Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS is a 10-item scale completed by clinic personnel that assesses the subject's symptoms of depression. Each question is answered on a 7-point scale ranging from no symptoms to worst possible symptoms. The total score is summed for all responses and ranges from 0 to 60. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: Baseline
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 31.4 Scores on a Scale | Standard Deviation 3.99 |
| onabotulinumtoxinA 30 U | Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 32.0 Scores on a Scale | Standard Deviation 4.12 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 32.4 Scores on a Scale | Standard Deviation 5.34 |
| onabotulinumtoxinA 50 U | Baseline Values for the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 32.0 Scores on a Scale | Standard Deviation 4.44 |
Primary
Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS is a 10-item scale completed by clinic personnel that assesses the subject's symptoms of depression. Each question is answered on a 7-point scale ranging from no symptoms to worst possible symptoms. The total score is summed for all responses and ranges from 0 to 60. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: Week 6
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -7.9 Scores on a Scale | Standard Error 1.4 |
| onabotulinumtoxinA 30 U | Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -11.6 Scores on a Scale | Standard Error 1.4 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -12.9 Scores on a Scale | Standard Error 1.2 |
| onabotulinumtoxinA 50 U | Change From Baseline Values in the Clinic 10-Item Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | -11.5 Scores on a Scale | Standard Error 1.2 |
Secondary
Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score
The CGI-S is a 7-point scale assessed by the clinician to rate the severity of the subject's symptoms. Scores range from 1 to 7, from normal (1, not at all ill) to among the most extremely ill patients (7). A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: Baseline
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | 4.2 Scores on a Scale | Standard Deviation 0.43 |
| onabotulinumtoxinA 30 U | Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | 4.4 Scores on a Scale | Standard Deviation 0.53 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | 4.4 Scores on a Scale | Standard Deviation 0.53 |
| onabotulinumtoxinA 50 U | Baseline Values for the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | 4.5 Scores on a Scale | Standard Deviation 0.5 |
Secondary
Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17)
The HAM-D17 is assessed by the clinician based on subject interview. The total scores range from 0 to 53. A higher total score indicates more severe depression. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: Baseline
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | 23.7 Scores on a Scale | Standard Deviation 3.15 |
| onabotulinumtoxinA 30 U | Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | 24.5 Scores on a Scale | Standard Deviation 3.03 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | 23.3 Scores on a Scale | Standard Deviation 2.94 |
| onabotulinumtoxinA 50 U | Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | 23.0 Scores on a Scale | Standard Deviation 3.32 |
Secondary
Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score
The CGI-S is a 7-point scale assessed by the clinician to rate the severity of the subject's symptoms. Scores range from 1 to 7, from normal (1, not at all ill) to among the most extremely ill patients (7). A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: 24 Weeks
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | -1.4 Scores on a Scale | Standard Error 0.2 |
| onabotulinumtoxinA 30 U | Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | -1.9 Scores on a Scale | Standard Error 0.2 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | -2.6 Scores on a Scale | Standard Error 0.2 |
| onabotulinumtoxinA 50 U | Change From Baseline Values in the 7-Item Clinical Global Impression of Severity of Illness (CGI-S) Score | -2.9 Scores on a Scale | Standard Error 0.2 |
Secondary
Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17)
The HAM-D17 is assessed by the clinician based on subject interview. The total scores range from 0 to 53. A higher total score indicates more severe depression. A negative change from baseline indicates an improvement in symptoms and a positive change from baseline indicates a worsening.
Time frame: 24 Weeks
Population: Modified Intent to Treat: Enrolled subjects who received treatment with data at the noted time point
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Normal Saline) for onabotulinumtoxinA 30 U | Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | -11.5 Scores on a Scale | Standard Error 1.1 |
| onabotulinumtoxinA 30 U | Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | -13.4 Scores on a Scale | Standard Error 1.1 |
| Placebo (Normal Saline) for onabotulinumtoxinA 50 U | Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | -16.1 Scores on a Scale | Standard Error 0.8 |
| onabotulinumtoxinA 50 U | Change From Baseline Values in the Clinic Hamilton Depression Rating Scale 17-Item Version (HAM-D17) | -17.4 Scores on a Scale | Standard Error 0.8 |