Bipolar Affective Psychosis, Bipolar Disorder, Mania, Manic Disorder, Manic State
Conditions
Keywords
Bipolar Disorder, Bipolar Affective Psychosis, Mania, Manic Disorder, Manic State
Brief summary
The primary purpose of the study is to assess the efficacy of Quetiapine extended release 600mg per day either as monotherapy or combined therapy in the treatment of patients with mania associated to Bipolar disorder. This trial will also assess the life quality and productivity loss improvement for patients from baseline to day 21.
Interventions
DRUGQuetiapine 600mg
300 mg quetiapine fumarate tablets for oral use. Day 1: One 300 mg tablet in the evening Day 2: Two 300 mg tablet in the evening Day 3 and onwards: Two 300 mg tablets in the evening, efforts must be done to maintain a daily dose of 600 mg/day.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type I Bipolar Disorder in Manic phase according to standard scales and physician criteria. * Patients of both genders, aged 18-65 years old being at the first episode * Patients with chronic Bipolar Disorder with at least one previous manic episode 6 months before inclusion, that based on the physician experience are in a manic episode at study entry quality
Exclusion criteria
* Psychoactive substance or alcohol abuse or dependence, forbidden medication, pregnancy, rapid cycling patients, intolerance to Quetiapine, clinically severe disease, unstable Diabetes Mellitus, neutropenia, other laboratory abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to End of Treatment (Day 21) | Baseline and 3 weeks | Change in the YMRS total score from baseline to Final Visit or Last Observation Carried Forward (LOCF), modified intention to treat (mITT) population. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 3 | Baseline and 2 weeks | Change in the YMRS total score from baseline to visit 3(2 weeks). YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0-60. |
| Number of Participants With Young Mania Rating Scale (YMRS) Response at Final Visit or Last Observation Carried Forward (LOCF) | 21 days ± 2 days or Last Observation Carried Forward | Number of participants that had Young Mania Rating Scale (YMRS) response at Final Visit or Last Observation Carried Forward (LOCF). A patient is scored as responder if the change from inclusion shows a reduction of 6 points in the YMRS total score. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60. |
| Number of Participants With Young Mania Rating Scale (YMRS) Remission at Final Visit or Last Observation Carried Forward (LOCF). | 21 days ± 2 days or Last Observation Carried Forward | Number of participants that had Young Mania Rating Scale (YMRS) remission at Final Visit or Last Observation Carried Forward (LOCF). A patient is classified in remission if his/her final YMRS total score was ≤11. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60. |
| Change in the Clinical Global Impression (CGI) Total Score From Baseline (CGI-S) to Final Visit or Last Observation Carried Forward (LOCF)(CGI-I). | Baseline and 3 weeks | Clinical Global Impression-Severity(CGI-S)is a measurement of illness severity evaluated at baseline. Clinical Global Impression-Improvement(CGI-I)is a measurement of improvement taken at Final Visit (FV) or Last Observation Carried Forward(LOCF).Change CGI Total score is assessed with next equation: CGI-I total score at FV or LOCF - CGI-S score. CGI-S Questionnaire has a scale range 0-7. 0=patients who are not assessed, 1=Normal 7=the most extremely ill patients. CGI-I Questionnaire has a scale range 0-7. 0=patients who are not assessed, 1=Very much improved; 4= No change; 7=Very much worse. |
| Change in the Clinical Global Impression - Improvement (CGI-I) at Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | Change in the CGI- I at Final Visit or Last Observation Carried Forward (LOCF). CGI I Questionnaire has a one item with scale range 0 to 7. 0=patients who ere not assessed, 1=Very much improved; 4= No change; 7=Very much worse. |
| Change in the Quality of Life Questionnaire EQ5D Index From Baseline to End of the Study. | Baseline and 3 weeks | Total possible index score is 0-1(0=The worsen quality of life; 1=The best Quality of life). |
| Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 2. | Baseline and 1 week | Change in the YMRS total score from baseline to visit 2 (1 week) ,. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0-60. |
| Change in the Simpson-Angus Scale (SAS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | Change in the Simpson-Angus Scale (SAS) total score from baseline to Final Visit or Last Observation Carried Forward (LOCF). SAS Questionnaire has a 6 items with scale range 0 to 3 for each item.0=Normal; 3=Most abnormal. Total possible score is 0-18. |
| Change in the Barnes Akathisia Rating Scale (BARS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | Change in the BARS total score from baseline to Final Visit or Last Observation Carried Forward (LOCF). BARS Questionnaire has 4 items with scale range 0 to 3 for 3 items and 0 to 5 for 1 item. 0=Normal; 3 or 5=Most abnormal. Total possible score is 0-14. |
| Change in Weight From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | — |
| Change in Waist Circumference From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | — |
| Number of Participants With >7% Increase in Weight | Baseline and 3 weeks | Number of participants with \>7% increase in weight from baseline to end of study. |
| Change in the Quality of Life Questionnaire EQ5D Visual Analogue Scale (VAS) From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | Baseline and 3 weeks | Change from baseline to Final Visit or Last Observation Carried Forward (LOCF). Quality of Life Questionnaire (EQ5D) part 2 has 1 item with continuous scale range 0 to 100. 0=The worsen Quality of Life; 100=The best Quality of life. |
Countries
Mexico
Participant flow
Recruitment details
Type I Bipolar Disorder in manic phase with a YMRS (Young Mania Rating Scale) score ≥12 at study entry. Patients of both genders, 18 - 65 years old, with bipolar disorder I according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine 600 mg Quetiapine Extended release 600 mg per day either as monotherapy or combined therapy | 88 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Drug compliance | 3 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Protocol deviation | 2 |
| Overall Study | Usage of not allowed drugs | 6 |
Baseline characteristics
| Characteristic | Quetiapine 600 mg |
|---|---|
| Age Continuous | 36.51 Years STANDARD_DEVIATION 12.7 |
| Clinical Global Impression-Severity (CGI-S) total score | 5.00 Scores on a scale STANDARD_DEVIATION 0.8 |
| European Quality of Life 5 Dimensions (EQ5D) Questionnaire Index | 0.54 Scores on a scale STANDARD_DEVIATION 0.3 |
| European Quality of Life 5 Dimensions (EQ5D) Questionnaire Visual Analogue Scale (VAS) | 55 Scores on a scale STANDARD_DEVIATION 27.8 |
| Safety scales BARS | 1.78 Scores on a scale STANDARD_DEVIATION 2.4 |
| Safety scales SAS | 1.12 Scores on a scale STANDARD_DEVIATION 2.2 |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 35 Participants |
| Young Mania Rating Scale (YMRS) total score | 32.06 Scores on a scale STANDARD_DEVIATION 9 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 88 |
| serious Total, serious adverse events | 1 / 88 |
Outcome results
Primary
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to End of Treatment (Day 21)
Change in the YMRS total score from baseline to Final Visit or Last Observation Carried Forward (LOCF), modified intention to treat (mITT) population. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients (88). Patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to End of Treatment (Day 21) | -20.72 Scores on a scale | Standard Deviation 10.2 |
Secondary
Change in the Barnes Akathisia Rating Scale (BARS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF).
Change in the BARS total score from baseline to Final Visit or Last Observation Carried Forward (LOCF). BARS Questionnaire has 4 items with scale range 0 to 3 for 3 items and 0 to 5 for 1 item. 0=Normal; 3 or 5=Most abnormal. Total possible score is 0-14.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Barnes Akathisia Rating Scale (BARS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | 1.78 Scores on a scale | Standard Deviation 2.4 |
Secondary
Change in the Clinical Global Impression (CGI) Total Score From Baseline (CGI-S) to Final Visit or Last Observation Carried Forward (LOCF)(CGI-I).
Clinical Global Impression-Severity(CGI-S)is a measurement of illness severity evaluated at baseline. Clinical Global Impression-Improvement(CGI-I)is a measurement of improvement taken at Final Visit (FV) or Last Observation Carried Forward(LOCF).Change CGI Total score is assessed with next equation: CGI-I total score at FV or LOCF - CGI-S score. CGI-S Questionnaire has a scale range 0-7. 0=patients who are not assessed, 1=Normal 7=the most extremely ill patients. CGI-I Questionnaire has a scale range 0-7. 0=patients who are not assessed, 1=Very much improved; 4= No change; 7=Very much worse.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Clinical Global Impression (CGI) Total Score From Baseline (CGI-S) to Final Visit or Last Observation Carried Forward (LOCF)(CGI-I). | -3.95 Scores on a scale | Standard Deviation 0.9 |
Secondary
Change in the Clinical Global Impression - Improvement (CGI-I) at Final Visit or Last Observation Carried Forward (LOCF).
Change in the CGI- I at Final Visit or Last Observation Carried Forward (LOCF). CGI I Questionnaire has a one item with scale range 0 to 7. 0=patients who ere not assessed, 1=Very much improved; 4= No change; 7=Very much worse.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Clinical Global Impression - Improvement (CGI-I) at Final Visit or Last Observation Carried Forward (LOCF). | 1.67 Scores on a scale | Standard Deviation 1.2 |
Secondary
Change in the Quality of Life Questionnaire EQ5D Index From Baseline to End of the Study.
Total possible index score is 0-1(0=The worsen quality of life; 1=The best Quality of life).
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Quality of Life Questionnaire EQ5D Index From Baseline to End of the Study. | 0.31 Scores on a scale | Standard Deviation 0.3 |
Secondary
Change in the Quality of Life Questionnaire EQ5D Visual Analogue Scale (VAS) From Baseline to Final Visit or Last Observation Carried Forward (LOCF).
Change from baseline to Final Visit or Last Observation Carried Forward (LOCF). Quality of Life Questionnaire (EQ5D) part 2 has 1 item with continuous scale range 0 to 100. 0=The worsen Quality of Life; 100=The best Quality of life.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Quality of Life Questionnaire EQ5D Visual Analogue Scale (VAS) From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | 27.73 Scores on a scale | Standard Deviation 29.2 |
Secondary
Change in the Simpson-Angus Scale (SAS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF).
Change in the Simpson-Angus Scale (SAS) total score from baseline to Final Visit or Last Observation Carried Forward (LOCF). SAS Questionnaire has a 6 items with scale range 0 to 3 for each item.0=Normal; 3=Most abnormal. Total possible score is 0-18.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Simpson-Angus Scale (SAS) Total Score From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | 1.16 Scores on a scale | Standard Deviation 2.2 |
Secondary
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 2.
Change in the YMRS total score from baseline to visit 2 (1 week) ,. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0-60.
Time frame: Baseline and 1 week
Population: Outcome was comparing the data at baseline with the specific data at visit 2(not with the LOCF), since only 78 patients completed YMRS at visit 2 the number of patients analyzed is different respect to the LOCF (88).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 2. | -11.5 Scores on a scale | Standard Deviation 7.2 |
Secondary
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 3
Change in the YMRS total score from baseline to visit 3(2 weeks). YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0-60.
Time frame: Baseline and 2 weeks
Population: Outcome was comparing the data at baseline with the specific data at visit 3 (not with the LOCF), since only 79 patients completed YMRS at visit 3 the number of patients analyzed is different respect to the LOCF (88).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Visit 3 | -18.01 Scores on a scale | Standard Deviation 8.2 |
Secondary
Change in Waist Circumference From Baseline to Final Visit or Last Observation Carried Forward (LOCF).
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in Waist Circumference From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | -0.29 cm | Standard Deviation 3.9 |
Secondary
Change in Weight From Baseline to Final Visit or Last Observation Carried Forward (LOCF).
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine 600 mg | Change in Weight From Baseline to Final Visit or Last Observation Carried Forward (LOCF). | 0.27 Kg | Standard Deviation 1.9 |
Secondary
Number of Participants With >7% Increase in Weight
Number of participants with \>7% increase in weight from baseline to end of study.
Time frame: Baseline and 3 weeks
Population: Modified Intention to treat patients mITT- (88), for each outcome measure where mITT is evaluated, population is the group of patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine 600 mg | Number of Participants With >7% Increase in Weight | 1 Participants |
Secondary
Number of Participants With Young Mania Rating Scale (YMRS) Remission at Final Visit or Last Observation Carried Forward (LOCF).
Number of participants that had Young Mania Rating Scale (YMRS) remission at Final Visit or Last Observation Carried Forward (LOCF). A patient is classified in remission if his/her final YMRS total score was ≤11. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60.
Time frame: 21 days ± 2 days or Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine 600 mg | Number of Participants With Young Mania Rating Scale (YMRS) Remission at Final Visit or Last Observation Carried Forward (LOCF). | 49 Participants |
Secondary
Number of Participants With Young Mania Rating Scale (YMRS) Response at Final Visit or Last Observation Carried Forward (LOCF)
Number of participants that had Young Mania Rating Scale (YMRS) response at Final Visit or Last Observation Carried Forward (LOCF). A patient is scored as responder if the change from inclusion shows a reduction of 6 points in the YMRS total score. YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60.
Time frame: 21 days ± 2 days or Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine 600 mg | Number of Participants With Young Mania Rating Scale (YMRS) Response at Final Visit or Last Observation Carried Forward (LOCF) | 81 Participants |