Trial Outcomes & Findings for Adult Bipolar Mania (NCT NCT00931723)
NCT ID: NCT00931723
Last Updated: 2012-04-19
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).
COMPLETED
PHASE4
356 participants
Change in YMRS total score from baseline to Day 43.
2012-04-19
Participant Flow
This multicenter study was conducted between 24 June 2009 and 22 November 2010.
The study had an up to 28-day enrollment period (including a washout period lasting 7 to 28 days) and a 6-week double-blind treatment period. Patients were randomized to receive lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day or placebo+quetiapine XR 400 to 800 mg/day.
Participant milestones
| Measure |
Lithium+Quetiapine XR
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Overall Study
STARTED
|
173
|
183
|
|
Overall Study
COMPLETED
|
147
|
144
|
|
Overall Study
NOT COMPLETED
|
26
|
39
|
Reasons for withdrawal
| Measure |
Lithium+Quetiapine XR
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
11
|
13
|
|
Overall Study
Adverse Event
|
6
|
13
|
|
Overall Study
Lithium found in blood
|
0
|
1
|
|
Overall Study
Condition under investigation worsened
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Study-specific discontinuation criteria
|
1
|
1
|
|
Overall Study
Severe non-compliance to protocol
|
2
|
0
|
|
Overall Study
Safety reasons
|
0
|
1
|
|
Overall Study
Took prohibited concomitant medication
|
0
|
1
|
|
Overall Study
Lack or insufficient theraputic response
|
2
|
5
|
|
Overall Study
Sponsor decision
|
1
|
0
|
|
Overall Study
Late hospital discharge
|
1
|
0
|
Baseline Characteristics
Adult Bipolar Mania
Baseline characteristics by cohort
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=183 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
Total
n=356 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
37.9 Years
STANDARD_DEVIATION 12.71 • n=5 Participants
|
38.8 Years
STANDARD_DEVIATION 12.09 • n=7 Participants
|
38.3 Years
STANDARD_DEVIATION 12.39 • n=5 Participants
|
|
Sex: Female, Male
Female
|
72 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
134 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=5 Participants
|
121 Participants
n=7 Participants
|
222 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Change in YMRS total score from baseline to Day 43.Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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).
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)
|
-22.8 Scores on a scale
Standard Error 0.706 • Interval 0.706 to
|
-20.1 Scores on a scale
Standard Error 0.711 • Interval 0.711 to
|
SECONDARY outcome
Timeframe: 43 days (from baseline to Day 43)Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The number of patients with clinically significant response (defined as ≥50% reduction from baseline to Day 43 in the YMRS total score) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
The Number of Patients With Clinically Significant Response.
|
137 Participants
|
120 Participants
|
SECONDARY outcome
Timeframe: Days 8 to 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The number of patients with clinically significant remission (defined as YMRS total score ≤12) from Days 8 to 43) was calculated. The Young Mania Rating Scale 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. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Remission
|
125 Participants
|
105 Participants
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43.Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)
|
-2.5 Scores on a scale
Standard Error 0.079 • Interval 0.079 to
|
-2.2 Scores on a scale
Standard Error 0.080 • Interval 0.08 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)
|
1.7 Scores on a scale
Standard Error 0.085 • Interval 0.085 to
|
1.9 Scores on a scale
Standard Error 0.086 • Interval 0.086 to
|
SECONDARY outcome
Timeframe: Day 43.Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The number of patients with a CGI-BP-C of "Much" or "Very much" improved in overall bipolar illness assessment at Day 43 was calculated. The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Improvement of Overall Bipolar Illness
|
134 Participants
|
125 Participants
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43.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.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
|
-4.8 Scores on a scale
Standard Error 0.366 • Interval 0.366 to
|
-4.1 Scores on a scale
Standard Error 0.368 • Interval 0.368 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 individual-item scores and ranges from 30 to 210.A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score
|
-19.2 Scores on a scale
Standard Error 0.914 • Interval 0.914 to
|
-15.6 Scores on a scale
Standard Error 0.914 • Interval 0.914 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are 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. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in PANSS Activation Subscale Score
|
-7.1 Scores on a scale
Standard Error 0.281 • Interval 0.281 to
|
-5.9 Scores on a scale
Standard Error 0.283 • Interval 0.283 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in PANSS Positive Subscale Score
|
-8.1 Scores on a scale
Standard Error 0.316 • Interval 0.316 to
|
-7.0 Scores on a scale
Standard Error 0.316 • Interval 0.316 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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 1 (Elevated mood) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 1
|
-1.8 Scores on a scale
Standard Error 0.079 • Interval 0.079 to
|
-1.6 Scores on a scale
Standard Error 0.080 • Interval 0.08 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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 2 (increased motor activity-energy) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 2
|
-1.9 Scores on a scale
Standard Error 0.071 • Interval 0.071 to
|
-1.7 Scores on a scale
Standard Error 0.072 • Interval 0.072 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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 3 (sexual interest) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 3
|
-1.3 Scores on a scale
Standard Error 0.063 • Interval 0.063 to
|
-1.1 Scores on a scale
Standard Error 0.064 • Interval 0.064 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43The 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 4
|
-2.0 Scores on a scale
Standard Error 0.085 • Interval 0.085 to
|
-1.8 Scores on a scale
Standard Error 0.086 • Interval 0.086 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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 5 (Irritability) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 5
|
-3.1 Scores on a scale
Standard Error 0.109 • Interval 0.109 to
|
-2.8 Scores on a scale
Standard Error 0.110 • Interval 0.11 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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 6 (speech-rate and amount) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 6
|
-3.1 Scores on a scale
Standard Error 0.116 • Interval 0.116 to
|
-2.9 Scores on a scale
Standard Error 0.118 • Interval 0.118 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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. This analysis is for Item 7 (language-thought disorder) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 7
|
-1.5 Scores on a scale
Standard Error 0.071 • Interval 0.071 to
|
-1.4 Scores on a scale
Standard Error 0.072 • Interval 0.072 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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. This analysis is for Item 8 (content) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 8
|
-3.1 Scores on a scale
Standard Error 0.132 • Interval 0.132 to
|
-2.9 Scores on a scale
Standard Error 0.133 • Interval 0.133 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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. . This analysis is for Item 9 (disruptive-aggressive behavior) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Outcome measures
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 9
|
-2.5 Scores on a scale
Standard Error 0.088 • Interval 0.088 to
|
-2.1 Scores on a scale
Standard Error 0.089 • Interval 0.089 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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. This analysis is for Item 10 (appearance) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 10
|
-1.1 Scores on a scale
Standard Error 0.057 • Interval 0.057 to
|
-1.0 Scores on a scale
Standard Error 0.057 • Interval 0.057 to
|
SECONDARY outcome
Timeframe: Change from baseline to Day 43Population: 173/176 is modified intent to treat analysis set. The reason why is different from 173/183 is that there is 7 patients excluded from the analysis (1 patient who did not take study drug and 6 patients who did not have post treatment YMRS scores).
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. This analysis is for Item 11 (insight) 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
| Measure |
Lithium+Quetiapine XR
n=173 Participants
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=176 Participants
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Change From Baseline to Day 43 in Each YMRS Item Score No. 11
|
-1.4 Scores on a scale
Standard Error 0.069 • Interval 0.069 to
|
-1.2 Scores on a scale
Standard Error 0.070 • Interval 0.07 to
|
Adverse Events
Lithium+Quetiapine XR
Placebo+Quetiapine XR
Serious adverse events
| Measure |
Lithium+Quetiapine XR
n=173 participants at risk
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=183 participants at risk
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Psychiatric disorders
Mania
|
1.7%
3/173
|
3.3%
6/183
|
|
Psychiatric disorders
Aggression; Hostility
|
0.00%
0/173
|
0.55%
1/183
|
|
Infections and infestations
Gastroenteritis
|
0.58%
1/173
|
0.00%
0/183
|
|
Investigations
No Therapeutic Response
|
0.00%
0/173
|
0.55%
1/183
|
Other adverse events
| Measure |
Lithium+Quetiapine XR
n=173 participants at risk
Lithium 600 to 1800 mg/day+quetiapine XR 400 to 800 mg/day
|
Placebo+Quetiapine XR
n=183 participants at risk
Placebo+quetiapine XR 400 to 800 mg/day
|
|---|---|---|
|
Nervous system disorders
Tremor
|
15.6%
27/173
|
4.9%
9/183
|
|
Nervous system disorders
Somnolence
|
12.7%
22/173
|
5.5%
10/183
|
|
Nervous system disorders
Dizziness
|
6.4%
11/173
|
4.4%
8/183
|
|
Nervous system disorders
Headache
|
5.2%
9/173
|
6.0%
11/183
|
|
Nervous system disorders
Sedation
|
2.9%
5/173
|
1.6%
3/183
|
|
Nervous system disorders
Dysarthria
|
2.3%
4/173
|
1.1%
2/183
|
|
Gastrointestinal disorders
Constipation
|
9.2%
16/173
|
8.7%
16/183
|
|
Gastrointestinal disorders
Dry Mouth
|
8.1%
14/173
|
7.7%
14/183
|
|
Gastrointestinal disorders
Diarrhoea
|
4.6%
8/173
|
1.1%
2/183
|
|
Gastrointestinal disorders
Vomiting
|
4.6%
8/173
|
0.00%
0/183
|
|
Gastrointestinal disorders
Nausea
|
2.9%
5/173
|
1.6%
3/183
|
|
Psychiatric disorders
Insomnia
|
6.4%
11/173
|
6.6%
12/183
|
|
General disorders
Pyrexia
|
5.8%
10/173
|
4.9%
9/183
|
|
Investigations
Weight Increased
|
1.2%
2/173
|
2.7%
5/183
|
|
Metabolism and nutrition disorders
Increased Appetite
|
2.3%
4/173
|
0.55%
1/183
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER