Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients

Major Depressive Disorder Clinical Trial

— RUBY  

Official title:

A Randomised, 6-week, Multicentre, Open-label, Rater-blinded Parallel Group Study Comparing Quetiapine Extended Release Monotherapy and Augmentation With Lithium Augmentation in Patients With Treatment Resistant Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00789854
• Other study ID #: D1443L00044
• Status: Completed
• Phase: Phase 3
• First received: November 11, 2008
• Last updated: April 23, 2012
• Start date: November 2008
• Est. completion date: August 2009

Study information

• Verified date: April 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research CouncilAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyDenmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines InstituteSlovakia: State Institute for Drug ControlSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the efficacy of Quetiapine extended release (XR) in combination with an selective serotonin reuptake inhibitor (SSRI) or Venlafaxine versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine versus Quetiapine extended release monotherapy in subjects with treatment resistant depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. As an independent objective, the primary objective will also be evaluated in two subgroups of patients: (1) patients who were resistant to two previous antidepressant therapies and (2) in the subgroup of patients with one previous failure.

Description:

The secondary objectives of the study are to compare the effects of the three different treatment regimen as assessed by the following variables and, if applicable, by their changes from randomisation to week 6 (end of study). Additionally the time of onset of therapeutic effect will be assessed by evaluating efficacy data after the first four days (Day 4) of treatment as well as after the first week of treatment (Day 8). These analyses will also be performed in the subgroups of patients with 2 failed previous antidepressants and patients with 1 failure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 688
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of the following:296.2x MDD, Single Episode296.3x MDD, Recurrent Episode

• Current episode of depression present, at least 42 days prior to enrolment but not more than 18 months

• MADRS-Score = 25 at enrolment and randomisation

Exclusion Criteria:

• Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation

• Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status

• Patients who, in the investigator's judgment pose a current serious suicidal or homicidal risk, or have made a suicide attempt within the past 6 months

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder
• Treatment Resistant Depression

Intervention

Drug:
• Quetiapine XR
300 mg once daily (od)
• Lithium carbonate
900 mg once daily (od)
• SSRI/Venlafaxine
SSRI - doses within label, Venlafaxine dose up to 225 mg/day

Locations

Country	Name	City	State
Australia	Research Site	Brisbane	Queensland
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Everton Park	Queensland
Australia	Research Site	Frankston	Victoria
Australia	Research Site	Garran	Australian Capital Territory
Australia	Research Site	Gilberton	South Australia
Australia	Research Site	Heidelberg	Victoria
Australia	Research Site	Malvern	Victoria
Australia	Research Site	Prahran	Victoria
Australia	Research Site	Richmond	Victoria
Australia	Research Site	Townsville	Queensland
Austria	Research Site	Graz
Austria	Research Site	Klagenfurt
Austria	Research Site	Salzburg
Austria	Research Site	Wels
Austria	Research Site	Wien
Austria	Research Site	Wiener NEUSTADT
Belgium	Research Site	Assebroek
Belgium	Research Site	Diest
Belgium	Research Site	Liege
Belgium	Research Site	Tielt
Bulgaria	Research Site	Cerova Koria Village	Veliko Tarnovo
Bulgaria	Research Site	Kardjali
Bulgaria	Research Site	Pazardjik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Denmark	Research Site	Esbjerg N
Denmark	Research Site	Frederiksberg
Denmark	Research Site	Odense
Germany	Research Site	Aachen
Germany	Research Site	Achim
Germany	Research Site	Augsburg
Germany	Research Site	Bad Homburg
Germany	Research Site	Bad Honnef
Germany	Research Site	Bad Saarow
Germany	Research Site	Berlin
Germany	Research Site	Bielefeld
Germany	Research Site	Bochum
Germany	Research Site	Butzbach
Germany	Research Site	Chemnitz
Germany	Research Site	Dresden
Germany	Research Site	Duren
Germany	Research Site	Dusseldorf
Germany	Research Site	Ellwangen
Germany	Research Site	Erbach
Germany	Research Site	Gelsenkirchen
Germany	Research Site	Gutersloh
Germany	Research Site	Halle
Germany	Research Site	Hattingen
Germany	Research Site	Herborn
Germany	Research Site	Kassel
Germany	Research Site	Kothen
Germany	Research Site	Neu-isenburg
Germany	Research Site	Neubrandenburg
Germany	Research Site	Nurnberg
Germany	Research Site	Oldenburg
Germany	Research Site	Ostfildern
Germany	Research Site	Schwerin
Germany	Research Site	Stuttgart
Germany	Research Site	Westerstede
Germany	Research Site	Wurzburg
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Gyula
Hungary	Research Site	Nyiregyhaza
Italy	Research Site	Bolzano
Italy	Research Site	Bressanone	BZ
Italy	Research Site	Brunico	BZ
Italy	Research Site	Cagliari	CA
Italy	Research Site	Catania
Italy	Research Site	Napoli
Italy	Research Site	Pisa	PI
Italy	Research Site	Roma	RM
Italy	Research Site	Roma
Portugal	Research Site	Braga
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Santarem
Romania	Research Site	Bucharest
Romania	Research Site	Craiova
Romania	Research Site	Galati
Romania	Research Site	Sibiu
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Krupina
Slovakia	Research Site	Levice
Slovakia	Research Site	Liptovsky Mikulas
Slovakia	Research Site	Michalovce Stranany
Slovakia	Research Site	Presov
Slovakia	Research Site	Roznava
Slovakia	Research Site	Zilina-bytcica
Slovakia	Research Site	Zlate Moravce
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Salamanca	Castilla Leon
Spain	Research Site	Sama de Langreo	Asturias
Spain	Research Site	Vigo	Galicia
Spain	Research Site	Zamora	Castilla Leon
United Kingdom	Research Site	Addlestone	Surrey
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Harrow
United Kingdom	Research Site	Horsham	West Sussex
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Winnick	Warrington
United Kingdom	Research Site	Winsford

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Bulgaria,  Denmark,  Germany,  Hungary,  Italy,  Portugal,  Romania,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set)	Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.	6 weeks treatment	No
Primary	Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set)	Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.	6 weeks of treatment	No
Secondary	Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS =10, All Patients	Number of patients in remission, with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.	6 weeks of treatment	No
Secondary	Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =10, Patients With One Previous Treatment Failure	Number of patients in remission with one previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.	6 weeks of treatment	No
Secondary	Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =10, Patients With Two Previous Treatment Failure	Number of patients in remission with two previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.	6 weeks of treatment	No
Secondary	Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =8	Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score =8. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.	6 weeks of treatment	No
Secondary	Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =12	Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score =12. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.	6 weeks of treatment	No
Secondary	Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, All Patients	Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better	6 week of treatments	No
Secondary	Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, Patients With One Previous Treatment Failure	Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better	6 weeks of treatment	No
Secondary	Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, Patients With Two Previous Treatment Failure	Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better	6 weeks of treatment	No
Secondary	Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients	Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure	Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure	Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Clinical Global Impression Scale (CGI-S), All Patients	Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale form 1-7, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure	Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure	Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Beck Depression Inventory (BDI)	Self-rating assessment of depressive symptoms using Beck Depression Inventory (BDI). Scale from 0-63, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Pain, Measured by Visual Analog Scale (VAS)	Self-rating assessment of pain using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Anxiety Measured by Visual Analog Scale (VAS)	Self-rating assessment of anxiety using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.	6 weeks of treatment	No
Secondary	Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory	Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Anxiety Measured by STAI, Trait Anxiety Inventory	Self-rating assessment of anxiety measured by State-Trait Anxiety Inventory (STAI), trait anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4	Sleeping quality measured by Montgomery-Asberg Depression Rating Scale (MADRS) item 4 (reduced sleep) (Scale 0-6, where a lower value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)	Self-rated sleeping quality measured by PSQI (Scale 0-21, subscales 0-3, 18 questions, where a lower value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component	Self rating assessment of quality in life using SF-36, mental component (Scale 0-100, where a higher value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component	Self rating assessment of quality in life using SF-36, physical component (Scale 0-100, where a higher value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility	Self rating assessment of quality in life using EQ-5D utility (Scale 0-100, where a higher value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Work Productivity and Activity Impairment: General Health (WPAI:GH)	Self rating assessment of working productivity using WPAI:GH (Scale 0 to number of hours worked during a week multiplied with the salary in Euro, a lower value shows a larger improvement)	6 weeks of treatment	No
Secondary	Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients	The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm (225, 229 or 221).	6 weeks of treatment	Yes
Secondary	Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure	The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.	6 weeks of treatment	Yes
Secondary	Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures	The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.	6 week of treatments	Yes