A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00422162
First received: January 11, 2007
Last updated: July 22, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Duloxetine hydrochloride
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline [ Time Frame: Baseline to Weeks 1, 2, 3, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline [ Time Frame: Baseline to Weeks 1, 2, 3, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) [ Time Frame: 4 to 8 weeks ] [ Designated as safety issue: No ]
    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).

  • Clinical Global Impression of Severity (CGI-S) Scores at Each Visit [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Clinical Global Impression of Improvement (CGI-I) at Each Visit [ Time Frame: Weeks 1, 2, 3, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Patient Global Impression of Improvement (PGI-I) Score at Each Visit [ Time Frame: Weeks 1, 2, 3, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 [ Time Frame: Baseline and Weeks 4 and 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Responders [ Time Frame: 4 to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Patients Reaching Remission [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8.

  • Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication [ Time Frame: over 8 weeks ] [ Designated as safety issue: No ]
    Number of participants using medication for anxiety and sleep disturbances.

  • Number of Patients With Potentially Clinically Significant Laboratory Findings [ Time Frame: over 8 weeks ] [ Designated as safety issue: Yes ]
    Laboratory results that were potentially clinically significant.

  • Discontinuations Due to Adverse Events (AE) [ Time Frame: over 8 weeks ] [ Designated as safety issue: Yes ]
    Listing of adverse events (AE) that led to treatment discontinuation (DC).

  • Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study [ Time Frame: over 8 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline to Week 4 and Week 8 in Weight [ Time Frame: Baseline to Weeks 4 and 8 ] [ Designated as safety issue: Yes ]
    Change in weight = Post-baseline visit minus baseline.


Enrollment: 339
Study Start Date: February 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Duloxetine Hydrochloride (60 mg)

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
60 mg once or twice a day, by mouth
Other Names:
  • LY248686
  • Cymbalta
Drug: Placebo
placebo capsule by mouth
Experimental: Duloxetine Hydrochloride (120 mg)

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
60 mg once or twice a day, by mouth
Other Names:
  • LY248686
  • Cymbalta
Drug: Placebo
placebo capsule by mouth

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00422162

Locations
France
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Besancon, France
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Bordeaux, France
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Bully les Mines, France
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Chateau-Gontier, France
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Dijon, France
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Dole, France
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Fains Veel, France
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Jarnac, France
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La Charite sur Loire, France
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La Rochelle, France
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Limoges, France
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Marseille, France
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Montberon, France
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Montpellier, France
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Nimes, France
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Paris, France
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Saint-Dizier, France
Italy
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Firenze, Italy
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Foggia, Italy
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Messina, Italy
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Milano, Italy
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Pisa, Italy
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Roma, Italy
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Siena, Italy
Russian Federation
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Kazan, Russian Federation
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Lipetsk, Russian Federation
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Moscow, Russian Federation
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Nizhny Novgorod, Russian Federation
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Saratov, Russian Federation
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St. Petersburg, Russian Federation
South Africa
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Bryanston, South Africa
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Cape Town, South Africa
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George, South Africa
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Krugersdorp, South Africa
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Pretoria, South Africa
Sponsors and Collaborators
Eli Lilly and Company
Boehringer Ingelheim
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Additional Information:
Publications:
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00422162     History of Changes
Other Study ID Numbers: 10614, F1J-BI-HMES
Study First Received: January 11, 2007
Results First Received: August 25, 2009
Last Updated: July 22, 2011
Health Authority: Russia: Pharmacological Committee, Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
South Africa: National Health Research Ethics Council
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Duloxetine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Analgesics
Antidepressive Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014