Trial Outcomes & Findings for Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder (NCT NCT00672490)

Last Updated: 2012-07-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

376 participants

Primary outcome timeframe

Baseline and 4 weeks

Results posted on

2012-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	Quetiapine Fumarate Used as Mono-Therapy Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Overall Study STARTED	187	189
Overall Study COMPLETED	163	157
Overall Study NOT COMPLETED	24	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Quetiapine Fumarate Used as Mono-Therapy Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Overall Study Withdrawal by Subject	8	8
Overall Study Lack of Compliance	2	7
Overall Study Mismatch Include/Exclude Criteria	1	0
Overall Study Adverse Event	5	8
Overall Study Violation of Concomitant Medicine	1	0
Overall Study Intolerance	0	2
Overall Study Lost to Follow-up	1	5
Overall Study No reason was provided	6	2

Baseline Characteristics

Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day	Total n=376 Participants Total of all reporting groups
Age Continuous	34.3 years STANDARD_DEVIATION 12.16 • n=5 Participants	32.43 years STANDARD_DEVIATION 11.14 • n=7 Participants	33.36 years STANDARD_DEVIATION 11.68 • n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	87 Participants n=7 Participants	181 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants	102 Participants n=7 Participants	195 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks

Population: Per Protocol Population

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=178 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=178 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)	-25.7 score on a scale Standard Deviation 13.7	-26.1 score on a scale Standard Deviation 13.4

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Change From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)	-2.65 score on a scale Standard Deviation 0.115	-0.17 score on a scale Standard Deviation 0.144

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)	-16.12 units on a scale Standard Deviation 0.285	-16.44 units on a scale Standard Deviation 0.28

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The MADRS is a 10-item scale that evaluates depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. Higher MADRS scores indicate higher levels of depressive symptoms. The MADRS total score is the sum of all 10 individual-item scores and ranges from 0 to 60.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)	-2.99 score on a scale Standard Deviation 0.181	-3.02 score on a scale Standard Deviation 0.179

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 4 (sleep) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment	-2.0 score on a scale Standard Deviation 1.2	-2.1 score on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: From Baseline to 4 weeks

The number of patients with clinically response (defined as ≥50% reduction in the YMRS total score from baseline to Day 28) was calculated. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Response Rate (Number of Patients With Clinically Response)	139 Participants	153 Participants

SECONDARY outcome

Timeframe: From Baseline to 4 weeks

The number of patients with clinically significant remission (defined as YMRS total score ≤12) at Day 28 was calculated. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania. Total score ≤12 indicates remission.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Remission Rate (Number of Patients With Clinically Significant Remission)	117 Participants	123 Participants

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and each item is rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS activation subscale score for effect on agitation and aggression is the sum of 6 PANSS individual items (ie, hostility, poor impulse control, excitement, uncooperativeness, poor rapport and tension) and ranges from 6 to 42.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)	-5.4 score on a scale Standard Deviation 4.5	-5.8 score on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The PANSS Supplemental Aggression Risk subscale score is the sum of 3 standard PANSS items - Excitement, Hostility and Depression - and 3 supplemental PANSS items related to anger - Anger, Difficulty in Delaying Gratification and Affective Lability and ranges from 6 to 42, where 6 is the "best" and 42 the "worst" score for the combined scale.

Outcome measures

Outcome measures
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 Participants Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 Participants Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)	-6.8 score on a scale Standard Deviation 5.1	-7.3 score on a scale Standard Deviation 5.1

Adverse Events

Quetiapine Fumarate Used as Mono-Therapy

Serious events: 0 serious events

Other events: 120 other events

Deaths: 0 deaths

Quetiapine Fumarate Used as Adjunct Therapy

Serious events: 1 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 participants at risk Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 participants at risk Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Musculoskeletal and connective tissue disorders Injury	0.00% 0/187	0.53% 1/189

Other adverse events

Other adverse events
Measure	Quetiapine Fumarate Used as Mono-Therapy n=187 participants at risk Quetiapine Fumarate 600 to 800 mg/day	Quetiapine Fumarate Used as Adjunct Therapy n=189 participants at risk Quetiapine Fumarate 600 to 800 mg/day + lithium 500 mg to 2000 mg/day
Gastrointestinal disorders Constipation	7.0% 13/187	12.7% 24/189
Gastrointestinal disorders Nausea	2.1% 4/187	7.9% 15/189
Gastrointestinal disorders Vomiting	0.53% 1/187	5.3% 10/189
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.5% 14/187	6.3% 12/189
Investigations Weight Increased	6.4% 12/187	8.5% 16/189
Nervous system disorders Dizziness	11.2% 21/187	7.4% 14/189
Nervous system disorders Extrapyramidal Symptom	3.2% 6/187	6.3% 12/189
Nervous system disorders Somnolence	5.3% 10/187	5.3% 10/189
Nervous system disorders Tremor	2.7% 5/187	6.9% 13/189
Cardiac disorders Tachycardia	5.9% 11/187	3.7% 7/189
Cardiac disorders Palpitations	3.7% 7/187	2.1% 4/189
Endocrine disorders Hypothyroidism	0.00% 0/187	4.2% 8/189
Gastrointestinal disorders Diarrhoea	1.6% 3/187	4.8% 9/189
Gastrointestinal disorders Dry mouth	1.6% 3/187	3.2% 6/189
General disorders Fatigue	2.1% 4/187	3.2% 6/189
Investigations Liver function test abnormal	4.3% 8/187	4.8% 9/189
Metabolism and nutrition disorders Hyperlipidemia	1.6% 3/187	3.7% 7/189
Nervous system disorders Hypersomnia	7.0% 13/187	4.8% 9/189

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER