Major Depressive Disorder Without Psychotic Features
Conditions
Keywords
Depression, Antidepressant, Antipsychotic
Brief summary
This is a 6-week comparison of asenapine versus placebo as an add-on to ongoing antidepressant treatment in patients with major depression who have not had a complete therapeutic response to treatment with the antidepressant alone. The investigators hypothesize that added asenapine will produce greater reductions in depression than will added placebo.
Detailed description
The investigators will undertake a 6-week, double-blind, randomized, parallel-group, placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis who have had an incomplete therapeutic response to treatment with an antidepressant medication alone.
Interventions
DRUGAsenapine 5-20 mg daily
5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID
DRUGPlacebo 1-4 tablets daily
One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID
Sponsors
Merck Sharp & Dohme LLC
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
-130 male or female patients, 18-65 years of age, with: 1. DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by the Mini-International Neuro-psychiatric Interview (MINI) 2. MADRS total score \> 20, and item 1 (Apparent Sadness) score \> 2 at enrollment and randomization 3. Inadequate therapeutic response during their current depressive episode; an inadequate therapeutic response will be defined as continued depressive psychopathology (see criterion 2) following \> six weeks of therapy at adequate doses (according to the US label) of any non-tricyclic, non-MAOI antidepressant medication
Exclusion criteria
1. Additional DSM-IV Axis I diagnoses other than Generalized Anxiety Disorder, Panic Disorder with or without Agoraphobia, or Social Phobia within 6 months prior to enrollment 2. DSM-IV Axis II diagnoses that significantly impact the current psychiatric status 3. Current MDD episode lasting \> 12 months 4. Electroconvulsive therapy within the preceding 6 months 5. Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior to enrollment 6. Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or dementia (MMSE \<24) 7. Risk of suicide as defined by MADRS item 10 score \> 4 8. Prior failure to respond to asenapine 9. Pregnancy or failure to use an acceptable form of birth control. Pregnancy as determined by serum pregnancy test at baseline 10. Hepatic impairment and history of low WBC, by medical history and interview.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MADRS Total Score | Baseline, 6 weeks | The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Completion Rate | 6 weeks | The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks |
| Clinical Response Rate | Baseline, 6 weeks | Clinical Response rate will be defined as the number of participants with a \> 50% reduction from baseline in MADRS total score. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. |
| Clinical Remission Rate | 6 weeks | Clinical Remission will be defined as the number of participants with a MADRS total score \< 7. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. |
| Rates of Sustained Remission | 2, 4, 6 weeks | Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS \< 7) is present. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine 5-20 mg Daily Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability
Asenapine 5-20 mg daily: 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID | 23 |
| Placebo 1-4 Tablets Daily Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability
Placebo 1-4 tablets daily: One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | Asenapine 5-20 mg Daily | Placebo 1-4 Tablets Daily | Total |
|---|---|---|---|
| Age, Continuous | 44.39 years STANDARD_DEVIATION 11.34 | 45.87 years STANDARD_DEVIATION 12.016 | 45.13 years STANDARD_DEVIATION 11.59 |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 23 | 16 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Change in MADRS Total Score
The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: Baseline, 6 weeks
Population: Analysis includes those participants who completed week 6 assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 5-20 mg Daily | Change in MADRS Total Score | -14.29 units on a scale | Standard Deviation 9.73 |
| Placebo 1-4 Tablets Daily | Change in MADRS Total Score | -11.61 units on a scale | Standard Deviation 11.82 |
Secondary
Clinical Remission Rate
Clinical Remission will be defined as the number of participants with a MADRS total score \< 7. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5-20 mg Daily | Clinical Remission Rate | 5 participants |
| Placebo 1-4 Tablets Daily | Clinical Remission Rate | 5 participants |
Secondary
Clinical Response Rate
Clinical Response rate will be defined as the number of participants with a \> 50% reduction from baseline in MADRS total score. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: Baseline, 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5-20 mg Daily | Clinical Response Rate | 7 participants |
| Placebo 1-4 Tablets Daily | Clinical Response Rate | 12 participants |
Secondary
Rates of Sustained Remission
Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS \< 7) is present. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Time frame: 2, 4, 6 weeks
Population: Participants that completed all data collection timepoints at week 2, 4, 6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5-20 mg Daily | Rates of Sustained Remission | 4 participants |
| Placebo 1-4 Tablets Daily | Rates of Sustained Remission | 4 participants |
Secondary
Study Completion Rate
The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5-20 mg Daily | Study Completion Rate | 60.87 percentage of participants |
| Placebo 1-4 Tablets Daily | Study Completion Rate | 100 percentage of participants |