A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00422162
• Other study ID #: 10614
• Secondary ID: F1J-BI-HMES
• Status: Completed
• Phase: Phase 4
• First received: January 11, 2007
• Last updated: July 22, 2011
• Start date: February 2007
• Est. completion date: August 2008

Study information

• Verified date: July 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Pharmacological Committee, Ministry of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthSouth Africa: National Health Research Ethics CouncilFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 339
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Duloxetine hydrochloride
60 mg once or twice a day, by mouth
• Placebo
placebo capsule by mouth

Locations

Country	Name	City	State
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Besancon
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Bordeaux
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Bully les Mines
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Chateau-Gontier
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Dijon
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Dole
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Fains Veel
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Jarnac
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	La Charite sur Loire
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	La Rochelle
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Limoges
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Marseille
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Montberon
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Montpellier
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Nimes
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Paris
France	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Saint-Dizier
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Firenze
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Foggia
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Messina
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Milano
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Pisa
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Roma
Italy	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Siena
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Kazan
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Lipetsk
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Moscow
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Nizhny Novgorod
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Saratov
Russian Federation	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	St. Petersburg
South Africa	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Bryanston
South Africa	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Cape Town
South Africa	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	George
South Africa	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Krugersdorp
South Africa	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician	Pretoria

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Boehringer Ingelheim

Countries where clinical trial is conducted

France,  Italy,  Russian Federation,  South Africa, 

References & Publications (1)

Brecht S, Desaiah D, Marechal ES, Santini AM, Podhorna J, Guelfi JD. Efficacy and safety of duloxetine 60 mg and 120 mg daily in patients hospitalized for severe depression: a double-blind randomized trial. J Clin Psychiatry. 2011 Aug;72(8):1086-94. doi: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Patients Reaching Remission	Major Depressive Disorder remission was defined as a total MADRS score =12 at Week 8.	Week 8	No
Secondary	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	No
Secondary	Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication	Number of participants using medication for anxiety and sleep disturbances.	over 8 weeks	No
Secondary	Number of Patients With Potentially Clinically Significant Laboratory Findings	Laboratory results that were potentially clinically significant.	over 8 weeks	Yes
Secondary	Discontinuations Due to Adverse Events (AE)	Listing of adverse events (AE) that led to treatment discontinuation (DC).	over 8 weeks	Yes
Secondary	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	Yes
Secondary	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	Yes

External Links

•   Lilly Clinical Trial Registry