Efficacy and Safety of Quetiapine Versus Quetiapine Plus Lithium in Bipolar Depression (QUALITY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00883493
First received: April 16, 2009
Last updated: July 2, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to compare the efficacy of quetiapine fumarate monotherapy with quetiapine fumarate in combination with lithium in the treatment of a major depressive episode in patients with bipolar disorder.


Condition Intervention Phase
Acute Bipolar Depression
Drug: Quetiapine fumarate XR
Drug: Lithium carbonate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, Multi-Centre Study to Compare the Efficacy and Safety of Extended Release Quetiapine Fumarate (Seroquel XR TM) Tablets as Mono-Therapy or in Combination With Lithium in the Treatment of Patients With Acute Bipolar Depression

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]

    The change of MADRS Total Score from baseline to the end of treatment was calculated by subtracting the MADRS Total Score assessed at week 8 from the baseline one (Baseline - 8 weeks).

    The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.



Secondary Outcome Measures:
  • Response Rate for MADRS. [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]

    Response rate defined as the percentage of patients with a ≥50% reduction from baseline in the MADRS total score to the final assessment at week 8.

    The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.


  • Hamilton Rating Scale for Depression (HAM-D) Total Score. [ Time Frame: Baseline, 8 Weeks ] [ Designated as safety issue: No ]

    The mean change of HAM-D Total Score from baseline to the end of treatment was calculated by subtracting the HAM-D Total Score assessed at week 8 from the baseline one (Baseline - week 8).

    HAM-D is a multiple choice questionnaire used to rate the severity of a patient's major depression. It consists of 17 different items with possible scores from 0 to 4 or 0 to 2 or 0 to 6 depending on the items. Sum the total of all seventeen items gives the HAM-D Total Score, which may range from 0 (min) to 53 (max). The higher the score, the more severe the depression.


  • Change in Hamilton Rating Scale for Anxiety (HAM-A) Total Score [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The mean change in HAM-A total score from baseline to final assessment was calculated by subtracting the HAM-A Total score assessed at week 8 from the total score assessed at the baseline (baseline - week 8).

    The HAM-A is a 14-item scale that assesses anxiety symptoms of anxiety such as "anxious mood", "tension" or "fears". Each item is scored on a 5-point scale, ranging from 0=not present to 4=severe. Sum the scores from all 14 parameters gives the HAM-A Total Score which may range from 0 (min) to 56 (max).


  • Change in the Clinical Global Impression Severity (CGI-S) Score. [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The reported mean change in the CGI-S score was calculated as baseline - week 8.

    CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. A patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.


  • Change in Young Mania Rating Scale (YMRS) Total Score. [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The YMRS is a rating scale to assess manic symptoms. The scale has 11 items and is based upon patient's subjective report of his or hers clinical condition over the previous 48 hours.

    The mean change in YMRS Total score reported was calculated as baseline - week 8.

    The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).


  • Change in the Pittsburgh Sleep Quality Index (PSQI)Total Score. [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]

    The mean change in PSQI score from baseline to final assessment at week 8 was calculated as baseline - week 8.

    PSQI evaluates 7 areas of quality and pattern of sleep: sleep quality, duration getting to sleep, sleep duration, sleep adequacy, sleep disturbance, use of sleeping pill, and somnolence). Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality.


  • Change in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Total Score. [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The mean change in (Q-LES-Q-Short Form) Total Score from baseline to week 8 was calculated by subtracting the 8 week value from baseline value (baseline - week 8).

    The Q-LES-Q-SF is a patient self assessment questionnaire consisting of 16 self-rated questions (1 being very poor - 5 very good); the first 14 will be incorporated into a total score. Higher scores indicate better quality of life.


  • Change in the Sheehan Disability Scale (SDS) Total Score. [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The mean change in the SDS Total score from baseline to week 8 (baseline- week 8).

    Sheehan Disability Scale is a 5 item scale, with a visual analog scale evaluating work/school work, social life and family life ranging from 0 to a maximum score of 30. Each one of the 3 domains is rated from 0-10 (no impairment to most severe impairment) with evaluation of not at all (0), mild (1-3), moderate (4-6), marked (7-9) and extreme (10) disability. A total score will be calculated. A score of 30 indicates most severe impairment.


  • Treatment Satisfaction Questionnaire (TSQ) Scores. [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]

    The 14-item TAQ questionnaire evaluates the patient's overall level of satisfaction with the study medication, the effectiveness, side effects and convenience of the medication.

    Effectiveness, side effects, convenience and global satisfaction is rated on a scale of 0 being the worst and 100 being very effective, no side effects or very convenient or very satisfied. Overall satisfaction is rated over a score of 5 and 5 being the best overall satisfaction.



Enrollment: 421
Study Start Date: April 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quetiapin fumarate XR
Quetiapine XR (extended release) will be administered once daily at bedtime in oral tablet form, Day 1: 50 mg, Day 2: 100 mg, Day 3: 200 mg, Day 4 onwards: 300 mg.
Drug: Quetiapine fumarate XR
Quetiapine XR (extended release) will be administered once daily at bedtime in oral tablet form, Day 1: 50 mg, Day 2: 100 mg, Day 3: 200 mg, Day 4 onwards: 300 mg.
Other Name: SEROQUEL XR
Experimental: Quetiapin fumarate XR+Lithium carbonate
Quetiapine XR will be administered like monotherapy arm. Lithium will be administered twice daily from Day 1 to Day 56.
Drug: Quetiapine fumarate XR
Quetiapine XR (extended release) will be administered once daily at bedtime in oral tablet form, Day 1: 50 mg, Day 2: 100 mg, Day 3: 200 mg, Day 4 onwards: 300 mg.
Other Name: SEROQUEL XR
Drug: Lithium carbonate
Twice daily from Day 1 to Day 56. From Day 1 to Day 7, the total daily dose of lithium could be increased gradually within the dose range 300 mg/day to 1800 mg/day. From Day 8 to Day 56, the total daily dose could be adjusted from 600 to 1800 mg/day
Other Names:
  • LITHURIL Tb in TURKEY
  • LITOCARB in PERU

  Eligibility

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

Inclusion Criteria:

  • Outpatients that meet the diagnostic criteria for bipolar disorder I and bipolar disorder II with the most recent episode depressed
  • The total score of the scale that's used for the evaluation of depression (HAM-D) should be ≥20
  • The total score of the scale that' used for the evaluation of mania (YMRS) should be ≤12

Exclusion Criteria:

  • Patients with a current DSM-IV-TR Axis I disorder other than bipolar disorder within 6 months of enrollment. Patients who pose a current serious suicidal or homicidal risk
  • Use of drugs that induce or inhibit the hepatic metabolizing enzymes within 14 days before randomisation
  • Patients who are unable to discontinue all psychoactive medications, including antidepressants, antipsychotics, and mood stabilizers at least 7 days prior to randomisation and consistent with the pharmacokinetics of the drug
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00883493

Locations
Argentina
Research Site
La Plata, Buenos Aires, Argentina
Research Site
Godoy Cruz, Mendoza, Argentina
Research Site
Caba, Argentina
Research Site
Mendoza, Argentina
Brazil
Research Site
Aparecida de Goiania, GO, Brazil
Research Site
Sao Paulo, SP, Brazil
Research Site
Rio de Janeiro, Brazil
Chile
Research Site
Santiago, Chile
Colombia
Research Site
Medellin, Antioquia, Colombia
Research Site
Bogota D.c, Cundinamarca, Colombia
Guatemala
Research Site
Guatemala, Ciudad de Guatemala, Guatemala
Mexico
Research Site
Monterrey, Nuevo Leon, Mexico
Research Site
Durango, Mexico
Research Site
Monterrey, Mexico
Research Site
San Luis Potosi, Mexico
Peru
Research Site
Lima, Peru
Turkey
Research Site
Ankara, Turkey
Research Site
Elazig, Turkey
Research Site
Istanbul, Turkey
Research Site
Izmir, Turkey
Research Site
Kocaeli, Turkey
Research Site
Malatya, Turkey
Research Site
Manisa, Turkey
Venezuela
Research Site
Caracas, Venezuela
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Simavi Vahip, Prof. Dr. Ege University Faculty of Medicine Psychiatry Department İzmir
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00883493     History of Changes
Other Study ID Numbers: D1443L00055
Study First Received: April 16, 2009
Results First Received: February 29, 2012
Last Updated: July 2, 2012
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Chile: Instituto de Salud Publica de Chile
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Guatemala: SUGEME (Independent Ethics Committe) y Comite de Farmacovigilancia
Mexico: National Institute of Public Health, Health Secretariat
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Ministry of Health
Venezuela: Instituto Nacional de Higiene
Turkey: Ministry of Health

Keywords provided by AstraZeneca:
Acute bipolar depression
Lithium carbonate
quetiapine fumarate
MADRS

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Lithium
Quetiapine
Lithium Carbonate
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

ClinicalTrials.gov processed this record on April 15, 2014