A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression

Study Overview
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Brief Summary
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An eight-week, randomized, double blind, two parallel groups, study to assess clinical response of duloxetine 60 milligrams (mg) and 120 mg per day in patients hospitalized for severe depression.

Official Title
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An Eight-Week, Randomized, Double Blind, Two Parallel Groups, Study to Assess Clinical Response of Duloxetine 60 mg and 120 Per Day in Patients Hospitalized for Severe Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Duloxetine hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients of ≥ 18 years of age that meet criteria for severe Major Depressive Disorder, without psychotic features (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, [DSM-IV] and confirmed by Mini International Neuropsychiatric Interview [MINI]). With a total score Montgomery-Asberg Depression Rating Scale (MADRS) ≥ 30 and 6-item Hamilton Depression Rating Scale (HAMD-6) ≥ 12 and Clinical Global Impression of Severity (CGI-Severity) ≥ 4 at both screening and baseline. Requirement of hospitalization (not for social or other non-medical reasons) at screening visit and at least up to Visit 4. Patients willing and able to comply with the requirement for hospitalization and with all scheduled visits, tests and procedures required by the protocol. Informed consent document must be signed at screening visit, in accordance with Good Clinical Practice (GCP) and local regulatory requirements, prior to any study procedure. Exclusion Criteria: More than two previous episodes of major depression that did not respond (according to investigator's opinion) to adequate doses and duration of two different antidepressant therapies. Lack of response to at least two antidepressant therapies given at adequate doses for at least 6 weeks for the current depressive episode. Concurrent presence of symptoms fulfilling criteria for any Axis I disorder other than anxiety disorders (with exception of the Obsessive-Compulsive Disorder (OCD)) or Major Depressive Disorder, in the investigator's judgment. Any previous diagnosis of a bipolar disorder, schizophrenia or OCD. Depression with catatonic features (according to DSM-IV), depression with post-partum onset, or organic mental disorders. The presence of an Axis II disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine Hydrochloride (60 mg)<br>Up to Week 4: 60 milligrams (mg) every morning and placebo every evening, by mouth (PO). Week 4 to Week 8: Responders continued on same dose as before; Nonresponders received 60 mg every morning and 60 mg every evening added to the placebo | Drug: Duloxetine hydrochloride<br>* 60 mg once or twice a day, by mouth<br>* Other names: Cymbalta;Drug: Placebo<br>* placebo capsule by mouth<br>|
| Experimental: Duloxetine Hydrochloride (120 mg)<br>Up to Week 4: 60 mg every morning and 60 mg every evening, PO. Week 4 to Week 8: Responders continued on same dose as before; Nonresponders continued as before with a placebo capsule added to the evening dose | Drug: Duloxetine hydrochloride<br>* 60 mg once or twice a day, by mouth<br>* Other names: Cymbalta;Drug: Placebo<br>* placebo capsule by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | The HAMD-6 (Items 1,2,7,8,10,13 from the 17-item HAMD) evaluates core symptoms of Major Depressive Disorder (MDD). Total scores range from 0 (normal) to 22 (severe). | Baseline to Weeks 1, 2, 3, 4, 6, 8 | 
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). | Baseline to Weeks 1, 2, 3, 4, 6, 8 | 
| Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and 6-Item Hamilton Depression Scale (HAMD-6) total scores were evaluated following dose up-titration in those patients who did not achieve the minimum 50% response for primary endpoint. MADRS is a rating scale for severity of depressive mood symptoms. Total scores range from 0 (low severity of symptoms) to 60 (high severity of symptoms). The HAMD-6, derived by the sum of HAMD-17 items 1, 2, 7, 8, 10 and 13, evaluates core symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). | 4 to 8 weeks | 
| Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, Weeks 1, 2, 3, 4, 6, 8 | 
| Clinical Global Impression of Improvement (CGI-I) at Each Visit | Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse). | Weeks 1, 2, 3, 4, 6, 8 | 
| Patient Global Impression of Improvement (PGI-I) Score at Each Visit | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). | Weeks 1, 2, 3, 4, 6, 8 | 
| Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | The HAMA scale measures anxiety symptoms accompanying Major Depressive Disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56. | Baseline and Weeks 4 and 8 | 
| Percentage of Responders | Patients with reduction in MADRS score ≥50% after 4 weeks were to stay on previous dose of duloxetine. Those with reduction in MADRS <50% were to receive 120 mg for remaining 4 weeks of treatment (up-titration from 60 mg to 120 mg for those randomized to 60 mg, and addition of placebo to 120 mg dose for those randomized to 120 mg). However, 2/70 patients randomized to 60 mg and then up-titrated to 120 mg after 4 weeks had reduction in MADRS ≥50% after 4 weeks, and 3/64 patients randomized to 120 mg and then given placebo in addition after 4 weeks had reduction in MADRS ≥50% after 4 weeks. | 4 to 8 weeks | 
| Patients Reaching Remission | Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8. | Week 8 | 
| Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | The RFL questionnaire is an instrument that evaluates patient's reasons for not committing suicide using a 6-point rating scale, where 1 is not at all important and 6 is extremely important. The questionnaire required participants to rate how important each item would be for living, if suicide was contemplated. Mean scores could range from 0 to 6. | Baseline and Week 8 | 
| Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Number of participants using medication for anxiety and sleep disturbances. | over 8 weeks | 
| Number of Patients With Potentially Clinically Significant Laboratory Findings | Laboratory results that were potentially clinically significant. | over 8 weeks | 
| Discontinuations Due to Adverse Events (AE) | Listing of adverse events (AE) that led to treatment discontinuation (DC). | over 8 weeks | 
| Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | Systolic and diastolic blood pressure and pulse rate were measured after 2 minutes rest in a supine position. High values were: diastolic blood pressure ≥90 mm Hg and increase from baseline of ≥10 mm Hg; systolic blood pressure ≥140 mm Hg and increase from baseline of ≥10 mm Hg; pulse rate ≥100 beats per minute (bpm) and an increase of ≥10 bpm from baseline. | over 8 weeks | 
| Change From Baseline to Week 4 and Week 8 in Weight | Change in weight = Post-baseline visit minus baseline. | Baseline to Weeks 4 and 8 |