Major Depressive Disorder (MDD)
Conditions
Brief summary
The purpose of this study is to assess nausea severity in response to four different drug dosing strategies of Duloxetine (30 mg with food, 60 mg with food, 30 mg without food, and 60 mg without food) in Korean patients with major depressive disorder (MDD).
Interventions
DRUGDuloxetine hydrochloride
po, QD
Sponsors
Boehringer Ingelheim
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For females of child-bearing potential test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. * 17-item Hamilton Depression Rating Scale (HAMD-17) total score \>15 at Screening and Randomization * Have signed the informed consent document (ICD) * Have a level of understanding sufficient to provide informed consent and to communicate with the investigators and site personnel * Are judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol * Patients must meet Diagnostic and Statistical Manual of Mental Disorders-fourth edition-text revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD). The Mini International Neuropsychiatric Interview (MINI) will be used to establish the diagnosis and exclude other psychiatric illnesses.
Exclusion criteria
* Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry * Have any current primary Axis I disorder other than MDD * Have any previous diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders * Lack of response of the current episode of major depression to two or more adequate courses of antidepressant therapy at clinically appropriate dose for a minimum of 4 weeks or, in the judgment of the investigator, the patient meets criteria for treatment-resistant depression * Have a history of a lack of response, at any time, to an adequate trial of duloxetine (defined as treatment with at least 60 mg/day of duloxetine for a minimum of 4 weeks) * Presence of an Axis II disorder that, in the judgment of the investigator, would interfere with study compliance * DSM-IV-TR-defined history of substance abuse or dependence within the past 6 months, excluding nicotine and caffeine * Patients judged to be at serious suicidal risk in the opinion of the investigator and/or score ≥3 on Item 3 (suicide) of the HAMD-17 * Serious medical illness or clinically significant laboratory abnormalities that, in the judgment of the investigator, are likely to require intervention/hospitalization/excluded medication during the course of the study Note: Patients with acute liver injury (such as hepatitis) or severe (Child-Pugh Class C) cirrhosis will be excluded * Have an acute or chronic medical illness with the main symptoms of nausea or gastrointestinal discomfort or taking any medication known to have major gastric effects that would interfere with nausea ratings. * Electroconvulsive therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within the past year * Taking any excluded medications within 7 days prior to Randomization. * Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Randomization or potential need to use a MAOI within 5 days after discontinuation of study drug. * Treatment with fluoxetine within 30 days prior to Randomization. * Frequent and/or severe allergic reactions with multiple medications or known hypersensitivity to duloxetine. * Abnormal thyroid stimulating hormone (TSH) concentration. Note: Participants diagnosed with hyperthyroidism or hypothyroidism who were treated with a stable dose of thyroid supplement for at least the past 3 months, have medically appropriate TSH concentration, and are clinically euthyroid, are allowed to enroll in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | 1 week and 8 weeks | AMDP-5 AE scale Item 112 (nausea) measured nausea severity during treatment (Week 0-8). The scores ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | Baseline, 1 week and 8 weeks | Gastric events scores (average of Item 112 \[nausea\] + Item 113 \[vomiting\]) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | Baseline, 1 week, 8 weeks | AMDP-5 common AEs score was used to create a composite measure of AEs from previous duloxetine studies (incidence \>5% and 2X placebo rate). The common AEs total score was the sum of the following 8 AMDP-5 items: 1) Mean of Item 112 (nausea) + 113 (vomiting); 2) Item 111 (dry mouth); 3) Item 115 (constipation); 4) Mean of Items 101-104 (insomnia); Item 122 (increased perspiration); 8) Item 106 (decreased appetite). Score was based on a 5-point scale: 1=absent, 2=mild, 3=moderate, 4=severe, 5=extremely severe; Higher score=worse severity. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | Baseline, 1 week, 8 weeks | The HAMD-17 total score ranged from 0 (not at all depressed)-52 (severely depressed). Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | Baseline, 1 week, 8 weeks | The HAMD-17 Maier subscale (Items 1, 2, 7, 8, 9, 10 of HAMD-17 questionnaire) represented the core symptoms of depression. Total subscale scores ranged from 0 (normal)-24 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | Baseline, 1 week, 8 weeks | The HAMD-17 Core Mood subscale (Items 1, 2, 3, 7, 8 of HAMD-17 questionnaire) represented the core symptoms of depression. Total subscale scores ranged from 0 (normal)-20 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | Baseline, 1 week, 8 weeks | The HAMD-17 Anxiety/Somatization subscale (Items 10, 11, 12, 13, 15, 17 of HAMD-17 questionnaire) evaluated the severity of psychic and somatic manifestations of anxiety and agitation. Total subscale scores ranged from 0 (normal)-18 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | Baseline, 1 week, 8 weeks | The HAMD-17 Retardation/Somatization subscale (Items 1, 7, 8, 14 of HAMD-17 questionnaire) evaluated dysfunction in mood, work, sexual activity, and overall motor retardation. Total subscale scores ranged from 0 (normal)-14 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Baseline, 8 weeks | Scores for AE scale Item 112 (nausea) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | Baseline, 1 week, 8 weeks | The CGI-S Rating Scale was a 7-point 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. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix. |
| Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 1 week, 8 weeks | The PGI-I Rating Scale was a 7-point scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction and an unstructured covariance matrix. |
| Time to Onset of Nausea | Baseline to onset of nausea (Baseline up to 8 weeks) | Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study. |
| Time to Resolve Nausea | Nausea onset up to nausea resolve (Baseline up to 8 weeks) | Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study. |
| Percentage of Participants Achieving Response | Baseline up to 8 weeks | Response was defined as ≥50% decrease from baseline on the 17-item Hamilton Depression Rating Scale (HAMD-17) total score. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed). |
| Percentage of Patients Achieving Remission | Baseline up to 8 weeks | Remission was defined as 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≤7. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed). |
| Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | Baseline, 1 week, 8 weeks | The HAMD-17 Sleep subscale (Items 4, 5, 6 of HAMD-17 questionnaire) evaluated initial, middle, and late insomnia. Total subscale scores ranged from 0 (no difficulty)-6 (difficulty). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix. |
Countries
South Korea
Participant flow
Pre-assignment details
Period 1 was a 3- to 30-day screening and washout period; Period 2 (Week 0-1) was a 1-week initial dosing period (randomization to duloxetine 30 mg with food, 30 mg without food, 60 mg with food, or 60 mg without food); Period 3 (Week 1-8) was a 7-week therapy period (treatment switched to duloxetine 60 mg once daily (QD) until study end.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 60 mg With Food Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks | 59 |
| Duloxetine 60 mg Without Food Duloxetine 60 mg capsule po QD without food for 8 weeks | 63 |
| Duloxetine 30 mg With Food Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks | 63 |
| Duloxetine 30 mg Without Food Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks | 64 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 (Screening and Washout) | Adverse Event | 1 | 2 | 1 | 1 |
| Period 1 (Screening and Washout) | Lost to Follow-up | 0 | 0 | 2 | 1 |
| Period 1 (Screening and Washout) | Protocol Violation | 1 | 0 | 0 | 0 |
| Period 1 (Screening and Washout) | Withdrawal by Subject | 1 | 2 | 1 | 1 |
| Period 3 (7-week Therapy Period) | Adverse Event | 17 | 15 | 10 | 12 |
| Period 3 (7-week Therapy Period) | Death | 0 | 0 | 1 | 0 |
| Period 3 (7-week Therapy Period) | Lack of Efficacy | 1 | 2 | 1 | 0 |
| Period 3 (7-week Therapy Period) | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Period 3 (7-week Therapy Period) | Protocol Violation | 10 | 4 | 3 | 11 |
| Period 3 (7-week Therapy Period) | Withdrawal by Subject | 2 | 2 | 4 | 2 |
Baseline characteristics
| Characteristic | Duloxetine 60 mg With Food | Duloxetine 60 mg Without Food | Duloxetine 30 mg With Food | Duloxetine 30 mg Without Food | Total |
|---|---|---|---|---|---|
| 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score | 21.0 units on a scale STANDARD_DEVIATION 5.18 | 22.3 units on a scale STANDARD_DEVIATION 5.69 | 22.9 units on a scale STANDARD_DEVIATION 5.45 | 20.3 units on a scale STANDARD_DEVIATION 5.23 | 21.6 units on a scale STANDARD_DEVIATION 5.46 |
| Age at first major depressive disorder (MDD) episode | 41.21 years | 43.33 years | 43.86 years | 41.58 years | 42.52 years |
| Age, Continuous | 44.65 years | 47.90 years | 49.94 years | 44.65 years | 46.81 years |
| Association for Methodology and Documentation in Psychiatry (AMDP-5) Item 112 (Nausea) Score | 0.3 units on a scale STANDARD_DEVIATION 0.72 | 0.2 units on a scale STANDARD_DEVIATION 0.59 | 0.2 units on a scale STANDARD_DEVIATION 0.61 | 0.1 units on a scale STANDARD_DEVIATION 0.38 | 0.2 units on a scale STANDARD_DEVIATION 0.58 |
| Body Mass Index (BMI) | 24.56 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.034 | 23.28 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.133 | 23.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.43 | 23.84 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.612 | 23.67 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.584 |
| Clinical Global Impression of Severity (CGI-S) Score | 4.4 units on a scale | 4.5 units on a scale | 4.7 units on a scale | 4.2 units on a scale | 4.4 units on a scale |
| Duration since first major depressive disorder (MDD) episode | 1.47 years | 2.65 years | 2.52 years | 1.29 years | 1.92 years |
| Number of previous MDD episodes/exacerbations in the last 24 months | 1.0 number of episodes in last 24 months | 1.0 number of episodes in last 24 months | 1.0 number of episodes in last 24 months | 1.0 number of episodes in last 24 months | 1.0 number of episodes in last 24 months |
| Previously diagnosed with major depressive disorder (MDD) | 59 participants | 63 participants | 63 participants | 64 participants | 249 participants |
| Race/Ethnicity, Customized Korean | 59 participants | 63 participants | 63 participants | 64 participants | 249 participants |
| Received previous therapy for current episode no | 41 participants | 38 participants | 45 participants | 38 participants | 162 participants |
| Received previous therapy for current episode yes | 18 participants | 25 participants | 18 participants | 26 participants | 87 participants |
| Region of Enrollment Korea, Republic of | 59 participants | 63 participants | 63 participants | 64 participants | 249 participants |
| Sex: Female, Male Female | 43 Participants | 47 Participants | 47 Participants | 40 Participants | 177 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 16 Participants | 24 Participants | 72 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 | 52 / 63 | 55 / 59 | 57 / 64 | 58 / 63 |
| serious Total, serious adverse events | 1 / 63 | 1 / 59 | 2 / 64 | 0 / 63 |
Outcome results
Primary
Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea)
AMDP-5 AE scale Item 112 (nausea) measured nausea severity during treatment (Week 0-8). The scores ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe.
Time frame: 1 week and 8 weeks
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 0-1 | 1.4 units on a scale |
| Duloxetine 60 mg With Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 1-8 (n=35; n=43; n=48; n=46) | 0.5 units on a scale |
| Duloxetine 60 mg Without Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 1-8 (n=35; n=43; n=48; n=46) | 0.5 units on a scale |
| Duloxetine 60 mg Without Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 0-1 | 1.2 units on a scale |
| Duloxetine 30 mg With Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 0-1 | 0.9 units on a scale |
| Duloxetine 30 mg With Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 1-8 (n=35; n=43; n=48; n=46) | 0.7 units on a scale |
| Duloxetine 30 mg Without Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 0-1 | 0.8 units on a scale |
| Duloxetine 30 mg Without Food | Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | Week 1-8 (n=35; n=43; n=48; n=46) | 0.4 units on a scale |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale
The HAMD-17 Anxiety/Somatization subscale (Items 10, 11, 12, 13, 15, 17 of HAMD-17 questionnaire) evaluated the severity of psychic and somatic manifestations of anxiety and agitation. Total subscale scores ranged from 0 (normal)-18 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 1-week change | -0.75 units on a scale | Standard Error 0.25 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.93 units on a scale | Standard Error 0.41 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.50 units on a scale | Standard Error 0.36 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 1-week change | -1.15 units on a scale | Standard Error 0.24 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 1-week change | -1.36 units on a scale | Standard Error 0.24 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.57 units on a scale | Standard Error 0.35 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 1-week change | -1.41 units on a scale | Standard Error 0.23 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.26 units on a scale | Standard Error 0.35 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale
The HAMD-17 Core Mood subscale (Items 1, 2, 3, 7, 8 of HAMD-17 questionnaire) represented the core symptoms of depression. Total subscale scores ranged from 0 (normal)-20 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 1-week change | -1.43 units on a scale | Standard Error 0.27 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 8-week change (n=28; n=37; n=39; n=37) | -6.18 units on a scale | Standard Error 0.4 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 8-week change (n=28; n=37; n=39; n=37) | -5.39 units on a scale | Standard Error 0.36 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 1-week change | -1.18 units on a scale | Standard Error 0.26 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 1-week change | -1.52 units on a scale | Standard Error 0.26 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 8-week change (n=28; n=37; n=39; n=37) | -5.85 units on a scale | Standard Error 0.35 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 1-week change | -1.76 units on a scale | Standard Error 0.25 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale | 8-week change (n=28; n=37; n=39; n=37) | -5.67 units on a scale | Standard Error 0.35 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale
The HAMD-17 Maier subscale (Items 1, 2, 7, 8, 9, 10 of HAMD-17 questionnaire) represented the core symptoms of depression. Total subscale scores ranged from 0 (normal)-24 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 1-week change | -2.06 units on a scale | Standard Error 0.33 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 8-week change (n=28; n=37; n=39; n=37) | -8.01 units on a scale | Standard Error 0.5 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 8-week change (n=28; n=37; n=39; n=37) | -7.12 units on a scale | Standard Error 0.45 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 1-week change | -1.90 units on a scale | Standard Error 0.32 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 1-week change | -2.15 units on a scale | Standard Error 0.32 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 8-week change (n=28; n=37; n=39; n=37) | -7.55 units on a scale | Standard Error 0.44 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 1-week change | -2.64 units on a scale | Standard Error 0.31 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale | 8-week change (n=28; n=37; n=39; n=37) | -7.30 units on a scale | Standard Error 0.44 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale
The HAMD-17 Retardation/Somatization subscale (Items 1, 7, 8, 14 of HAMD-17 questionnaire) evaluated dysfunction in mood, work, sexual activity, and overall motor retardation. Total subscale scores ranged from 0 (normal)-14 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 1-week change | -0.83 units on a scale | Standard Error 0.22 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.92 units on a scale | Standard Error 0.35 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.37 units on a scale | Standard Error 0.31 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 1-week change | -0.87 units on a scale | Standard Error 0.21 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 1-week change | -1.02 units on a scale | Standard Error 0.22 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.63 units on a scale | Standard Error 0.31 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 1-week change | -1.20 units on a scale | Standard Error 0.21 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale | 8-week change (n=28; n=37; n=39; n=37) | -4.55 units on a scale | Standard Error 0.31 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale
The HAMD-17 Sleep subscale (Items 4, 5, 6 of HAMD-17 questionnaire) evaluated initial, middle, and late insomnia. Total subscale scores ranged from 0 (no difficulty)-6 (difficulty). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 1-week change | -0.72 units on a scale | Standard Error 0.21 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 8-week change (n=28; n=37; n=39; n=37) | -2.77 units on a scale | Standard Error 0.27 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 8-week change (n=28; n=37; n=39; n=37) | -2.32 units on a scale | Standard Error 0.24 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 1-week change | -0.64 units on a scale | Standard Error 0.21 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 1-week change | -0.66 units on a scale | Standard Error 0.21 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 8-week change (n=28; n=37; n=39; n=37) | -2.09 units on a scale | Standard Error 0.23 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 1-week change | -1.01 units on a scale | Standard Error 0.2 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale | 8-week change (n=28; n=37; n=39; n=37) | -2.10 units on a scale | Standard Error 0.23 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score
The HAMD-17 total score ranged from 0 (not at all depressed)-52 (severely depressed). Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 1-week change | -2.83 units on a scale | Standard Error 0.57 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 8-week change (n=28; n=37; n=39; n=37) | -15.39 units on a scale | Standard Error 1.01 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 8-week change (n=28; n=37; n=39; n=37) | -13.45 units on a scale | Standard Error 0.9 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 1-week change | -2.85 units on a scale | Standard Error 0.55 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 1-week change | -3.84 units on a scale | Standard Error 0.56 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 8-week change (n=28; n=37; n=39; n=37) | -13.60 units on a scale | Standard Error 0.88 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 1-week change | -4.34 units on a scale | Standard Error 0.54 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 8-week change (n=28; n=37; n=39; n=37) | -13.07 units on a scale | Standard Error 0.89 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score
AMDP-5 common AEs score was used to create a composite measure of AEs from previous duloxetine studies (incidence \>5% and 2X placebo rate). The common AEs total score was the sum of the following 8 AMDP-5 items: 1) Mean of Item 112 (nausea) + 113 (vomiting); 2) Item 111 (dry mouth); 3) Item 115 (constipation); 4) Mean of Items 101-104 (insomnia); Item 122 (increased perspiration); 8) Item 106 (decreased appetite). Score was based on a 5-point scale: 1=absent, 2=mild, 3=moderate, 4=severe, 5=extremely severe; Higher score=worse severity.
Time frame: Baseline, 1 week, 8 weeks
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 1-week change | 1.25 units on a scale | Standard Error 0.44 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 8-week change (n=28; n=37; n=39; n=37) | -3.54 units on a scale | Standard Error 0.47 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 8-week change (n=28; n=37; n=39; n=37) | -2.99 units on a scale | Standard Error 0.42 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 1-week change | 1.28 units on a scale | Standard Error 0.42 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 1-week change | -0.00 units on a scale | Standard Error 0.43 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 8-week change (n=28; n=37; n=39; n=37) | -2.33 units on a scale | Standard Error 0.41 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 1-week change | -0.37 units on a scale | Standard Error 0.41 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score | 8-week change (n=28; n=37; n=39; n=37) | -3.23 units on a scale | Standard Error 0.41 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score
Gastric events scores (average of Item 112 \[nausea\] + Item 113 \[vomiting\]) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 1 week and 8 weeks
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 1-week change | 0.73 units on a scale | Standard Error 0.1 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 8-week change (n=28; n=37; n=39; n=37) | -0.04 units on a scale | Standard Error 0.04 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 8-week change (n=28; n=37; n=39; n=37) | -0.04 units on a scale | Standard Error 0.04 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 1-week change | 0.72 units on a scale | Standard Error 0.1 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 1-week change | 0.35 units on a scale | Standard Error 0.1 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 8-week change (n=28; n=37; n=39; n=37) | -0.04 units on a scale | Standard Error 0.04 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 1-week change | 0.37 units on a scale | Standard Error 0.1 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score | 8-week change (n=28; n=37; n=39; n=37) | -0.09 units on a scale | Standard Error 0.04 |
Secondary
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S)
The CGI-S Rating Scale was a 7-point 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. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix.
Time frame: Baseline, 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 1-week change | -0.36 units on a scale | Standard Error 0.09 |
| Duloxetine 60 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 8-week change (n=28; n=37; n=39; n=37) | -2.43 units on a scale | Standard Error 0.17 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 8-week change (n=28; n=37; n=39; n=37) | -2.13 units on a scale | Standard Error 0.15 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 1-week change | -0.36 units on a scale | Standard Error 0.09 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 1-week change | -0.44 units on a scale | Standard Error 0.09 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 8-week change (n=28; n=37; n=39; n=37) | -2.23 units on a scale | Standard Error 0.15 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 1-week change | -0.63 units on a scale | Standard Error 0.09 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S) | 8-week change (n=28; n=37; n=39; n=37) | -2.27 units on a scale | Standard Error 0.15 |
Secondary
Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea)
Scores for AE scale Item 112 (nausea) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Time frame: Baseline, 8 weeks
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken. N = number of subjects with a baseline and post-baseline result at the Week 8 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg With Food | Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | -0.02 units on a scale | Standard Error 0.08 |
| Duloxetine 60 mg Without Food | Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | -0.02 units on a scale | Standard Error 0.07 |
| Duloxetine 30 mg With Food | Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | -0.01 units on a scale | Standard Error 0.07 |
| Duloxetine 30 mg Without Food | Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea) | -1.12 units on a scale | Standard Error 0.07 |
Secondary
Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks
The PGI-I Rating Scale was a 7-point scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction and an unstructured covariance matrix.
Time frame: 1 week, 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg With Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 8-week change (n=28; n=37; n=39; n=37) | 2.31 units on a scale | Standard Error 0.19 |
| Duloxetine 60 mg With Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 1-week change | 3.72 units on a scale | Standard Error 0.13 |
| Duloxetine 60 mg Without Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 1-week change | 3.77 units on a scale | Standard Error 0.13 |
| Duloxetine 60 mg Without Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 8-week change (n=28; n=37; n=39; n=37) | 2.40 units on a scale | Standard Error 0.17 |
| Duloxetine 30 mg With Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 1-week change | 3.52 units on a scale | Standard Error 0.13 |
| Duloxetine 30 mg With Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 8-week change (n=28; n=37; n=39; n=37) | 2.36 units on a scale | Standard Error 0.16 |
| Duloxetine 30 mg Without Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 8-week change (n=28; n=37; n=39; n=37) | 2.40 units on a scale | Standard Error 0.16 |
| Duloxetine 30 mg Without Food | Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks | 1-week change | 3.47 units on a scale | Standard Error 0.12 |
Secondary
Percentage of Participants Achieving Response
Response was defined as ≥50% decrease from baseline on the 17-item Hamilton Depression Rating Scale (HAMD-17) total score. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed).
Time frame: Baseline up to 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine 60 mg With Food | Percentage of Participants Achieving Response | 51.8 percentage of participants |
| Duloxetine 60 mg Without Food | Percentage of Participants Achieving Response | 49.2 percentage of participants |
| Duloxetine 30 mg With Food | Percentage of Participants Achieving Response | 47.5 percentage of participants |
| Duloxetine 30 mg Without Food | Percentage of Participants Achieving Response | 47.5 percentage of participants |
Secondary
Percentage of Patients Achieving Remission
Remission was defined as 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≤7. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed).
Time frame: Baseline up to 8 weeks
Population: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine 60 mg With Food | Percentage of Patients Achieving Remission | 42.9 percentage of participants |
| Duloxetine 60 mg Without Food | Percentage of Patients Achieving Remission | 37.3 percentage of participants |
| Duloxetine 30 mg With Food | Percentage of Patients Achieving Remission | 35.6 percentage of participants |
| Duloxetine 30 mg Without Food | Percentage of Patients Achieving Remission | 32.8 percentage of participants |
Secondary
Time to Onset of Nausea
Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study.
Time frame: Baseline to onset of nausea (Baseline up to 8 weeks)
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine 60 mg With Food | Time to Onset of Nausea | 2.0 days |
| Duloxetine 60 mg Without Food | Time to Onset of Nausea | 1.0 days |
| Duloxetine 30 mg With Food | Time to Onset of Nausea | 7.0 days |
| Duloxetine 30 mg Without Food | Time to Onset of Nausea | 6.0 days |
Secondary
Time to Resolve Nausea
Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study.
Time frame: Nausea onset up to nausea resolve (Baseline up to 8 weeks)
Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine 60 mg With Food | Time to Resolve Nausea | 6.0 days |
| Duloxetine 60 mg Without Food | Time to Resolve Nausea | 8.0 days |
| Duloxetine 30 mg With Food | Time to Resolve Nausea | 15.0 days |
| Duloxetine 30 mg Without Food | Time to Resolve Nausea | 6.0 days |