Trial Outcomes & Findings for Effectiveness of Quetiapine XR on the Control of Symptoms of Manic Phase of Bipolar Disorder. (NCT NCT00521365)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

88 participants

Primary outcome timeframe

Baseline and 3 weeks

Results posted on

2012-07-17

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Quetiapine 600 mg Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Overall Study STARTED	88
Overall Study Modified Intention to Treat (mITT)	88
Overall Study Per Protocol (PP) Population	68
Overall Study Safety Analysis Set	88
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Quetiapine 600 mg Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Overall Study Adverse Event	3
Overall Study Lost to Follow-up	6
Overall Study Protocol deviation	2
Overall Study Drug compliance	3
Overall Study Usage of not allowed drugs	6

Baseline Characteristics

Effectiveness of Quetiapine XR on the Control of Symptoms of Manic Phase of Bipolar Disorder.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Quetiapine 600 mg n=88 Participants Quetiapine Extended release 600 mg per day either as monotherapy or combined therapy
Age Continuous	36.51 Years STANDARD_DEVIATION 12.70 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants
Young Mania Rating Scale (YMRS) total score	32.06 Scores on a scale STANDARD_DEVIATION 9.00 • n=5 Participants
Clinical Global Impression-Severity (CGI-S) total score	5.00 Scores on a scale STANDARD_DEVIATION 0.80 • n=5 Participants
European Quality of Life 5 Dimensions (EQ5D) Questionnaire Index	0.54 Scores on a scale STANDARD_DEVIATION 0.3 • n=5 Participants
European Quality of Life 5 Dimensions (EQ5D) Questionnaire Visual Analogue Scale (VAS)	55 Scores on a scale STANDARD_DEVIATION 27.8 • n=5 Participants
Safety scales SAS	1.12 Scores on a scale STANDARD_DEVIATION 2.20 • n=5 Participants
Safety scales BARS	1.78 Scores on a scale STANDARD_DEVIATION 2.40 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=78 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=79 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Number of Participants With Young Mania Rating Scale (YMRS) Response at Final Visit or Last Observation Carried Forward (LOCF)	81 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Number of Participants With Young Mania Rating Scale (YMRS) Remission at Final Visit or Last Observation Carried Forward (LOCF).	49 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

Total possible index score is 0-1(0=The worsen quality of life; 1=The best Quality of life).

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Change in Weight From Baseline to Final Visit or Last Observation Carried Forward (LOCF).	0.27 Kg Standard Deviation 1.90

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Change in Waist Circumference From Baseline to Final Visit or Last Observation Carried Forward (LOCF).	-0.29 cm Standard Deviation 3.90

SECONDARY outcome

Timeframe: 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.

Number of participants with \>7% increase in weight from baseline to end of study.

Outcome measures

Outcome measures
Measure	Quetiapine 600 mg n=88 Participants Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Number of Participants With >7% Increase in Weight	1 Participants

Adverse Events

Quetiapine 600 mg

Serious events: 1 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Quetiapine 600 mg n=88 participants at risk Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Nervous system disorders Mania Increased	1.1% 1/88

Other adverse events

Other adverse events
Measure	Quetiapine 600 mg n=88 participants at risk Once the patient was enrolled, he/she was provided with a bottle that contains enough tablets of quetiapine to complete up-titration regime and whole treatment as follows: 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. This study is a single arm study. All patients received quetiapine XR 600 mg.
Nervous system disorders Akathisia	2.3% 2/88
Nervous system disorders Cephalea	4.5% 4/88
Nervous system disorders Dizziness	3.4% 3/88
Gastrointestinal disorders Gastritis	2.3% 2/88
Blood and lymphatic system disorders Hypertriglycerides	2.3% 2/88
Nervous system disorders Somnolence	14.8% 13/88
Vascular disorders Tachycardia	2.3% 2/88
Nervous system disorders Tremor	2.3% 2/88
Nervous system disorders Anxiety	2.3% 2/88

Additional Information

Gerard Lynch

AstraZeneca

Phone: 09645895

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER