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Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients (RUBY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00789854
First received: November 11, 2008
Last updated: April 23, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Treatment Resistant Depression
 Drug: Quetiapine XR
Drug: Lithium carbonate
Drug: SSRI/Venlafaxine
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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) [ Time Frame: 6 weeks treatment ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients [ Time Frame: 6 week of treatments ] [ Designated as safety issue: No ]
    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

  • Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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

  • Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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

  • Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where lower value shows a larger improvement.

  • Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.

  • Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.

  • Change in Clinical Global Impression Scale (CGI-S), All Patients [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Change in Beck Depression Inventory (BDI) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self-rating assessment of depressive symptoms using Beck Depression Inventory (BDI). Scale from 0-63, where a lower value shows a larger improvement.

  • Change in Pain, Measured by Visual Analog Scale (VAS) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self-rating assessment of pain using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.

  • Change in Anxiety Measured by Visual Analog Scale (VAS) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self-rating assessment of anxiety using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.

  • Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)

  • Change in Anxiety Measured by STAI, Trait Anxiety Inventory [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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)

  • Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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)

  • Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self-rated sleeping quality measured by PSQI (Scale 0-21, subscales 0-3, 18 questions, where a lower value shows a larger improvement)

  • Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self rating assessment of quality in life using SF-36, mental component (Scale 0-100, where a higher value shows a larger improvement)

  • Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self rating assessment of quality in life using SF-36, physical component (Scale 0-100, where a higher value shows a larger improvement)

  • Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    Self rating assessment of quality in life using EQ-5D utility (Scale 0-100, where a higher value shows a larger improvement)

  • Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: No ]
    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)

  • Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: Yes ]
    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).

  • Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure [ Time Frame: 6 weeks of treatment ] [ Designated as safety issue: Yes ]
    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.

  • Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures [ Time Frame: 6 week of treatments ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 688
Study Start Date: November 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Add-on Quetiapine XR+SSRI/Venlafaxine

Selective serotonin reuptake inhibitors (SSRI) or Venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od).

From previous anti-depressant treatment 64% of the patients had SSRI and 35% had Venlafaxine at baseline.

 Drug: Quetiapine XR
300 mg once daily (od)
Other Name: Seroquel XR
Drug: SSRI/Venlafaxine
SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Active Comparator: Add-on Lithium+SSRI/Venlafaxine

Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od).

From previous anti-depressant treatment 67% of the patients had SSRI and 33% had Venlafaxine at baseline.

 Drug: Lithium carbonate
900 mg once daily (od)
Other Name: Quilonum Retard
Drug: SSRI/Venlafaxine
SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Active Comparator: Monotherapy Quetiapine XR
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
 Drug: Quetiapine XR
300 mg once daily (od)
Other Name: Seroquel XR

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00789854

  Show 106 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Michael Bauer, professor Germany
Study Director: Birgit Ekholm, PhD AstraZeneca MC Sweden
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00789854     History of Changes
Other Study ID Numbers: D1443L00044
Study First Received: November 11, 2008
Results First Received: August 4, 2010
Last Updated: April 23, 2012
Health Authority: Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Institute
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Depression
MDD
TRD

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Lithium
Quetiapine
Lithium Carbonate
Venlafaxine
Serotonin Uptake Inhibitors
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
 Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation

ClinicalTrials.gov processed this record on May 19, 2013