Trial Outcomes & Findings for Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression (NCT NCT01256177)

NCT ID: NCT01256177

Last Updated: 2016-04-15

Results Overview

MADRS total score range: 0 to 60, the higher the score, the more severe, Change : Total MADRS score at week 8 minus score at baseline

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 361 participants
• Primary outcome timeframe: Baseline to Week 8
• Results posted on: 2016-04-15

Participant Flow

A 56-days (8 week), multicenter, double-blind, randomized, parallel group, Phase III study was done to compare the efficacy and safety of quetiapine XR with placebo in the treatment of patients with bipolar depression. In total 296 patients were randomized in 19 centers in the China between December 2010 and November 2012.

361 patients were enrolled in the study of which 296 patients were randomized and 65 patients were not randomized. Reasons for patients not being randomized are (22 due to eligiblity criteria not fullfilled, 40 due to subject decision, 3 due to others).

Participant milestones

Measure	Placebo Placebo matching Quetiapine XR.	Quetiapine XR Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Overall Study STARTED	148	148
Overall Study COMPLETED	98	111
Overall Study NOT COMPLETED	50	37

Reasons for withdrawal

Measure	Placebo Placebo matching Quetiapine XR.	Quetiapine XR Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Overall Study Withdrawal by Subject	23	22
Overall Study Lost to Follow-up	2	2
Overall Study Adverse Event	8	9
Overall Study Severe Non-Compliance to Protocol	4	2
Overall Study Condition under Investigation Worsened	1	0
Overall Study Lack of Efficacy	11	2
Overall Study TG=593mg/dL, not fit to participate.	1	0

Baseline Characteristics

Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression

Baseline characteristics by cohort

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.	Total n=279 Participants Total of all reporting groups
Age, Continuous	32.8 Years STANDARD_DEVIATION 11.0 • n=93 Participants	33.4 Years STANDARD_DEVIATION 11.9 • n=4 Participants	33.1 Years STANDARD_DEVIATION 11.4 • n=27 Participants
Age, Customized 18 - 39 years	105 Participants n=93 Participants	102 Participants n=4 Participants	207 Participants n=27 Participants
Age, Customized 40 - 65 years	35 Participants n=93 Participants	37 Participants n=4 Participants	72 Participants n=27 Participants
Sex/Gender, Customized Female	73 Participants n=93 Participants	72 Participants n=4 Participants	145 Participants n=27 Participants
Sex/Gender, Customized Male	67 Participants n=93 Participants	67 Participants n=4 Participants	134 Participants n=27 Participants
Race/Ethnicity, Customized Race,Asian	140 Participants n=93 Participants	139 Participants n=4 Participants	279 Participants n=27 Participants
Race/Ethnicity, Customized Ethnicity, Chinese	140 Participants n=93 Participants	139 Participants n=4 Participants	279 Participants n=27 Participants
Weight	65.2 Kilogram (Kg) STANDARD_DEVIATION 12.3 • n=93 Participants	63.8 Kilogram (Kg) STANDARD_DEVIATION 13.5 • n=4 Participants	64.5 Kilogram (Kg) STANDARD_DEVIATION 12.9 • n=27 Participants
MADRS total score at baseline	28.8 Scores on a scale STANDARD_DEVIATION 5.3 • n=93 Participants	28.5 Scores on a scale STANDARD_DEVIATION 5.4 • n=4 Participants	28.6 Scores on a scale STANDARD_DEVIATION 5.3 • n=27 Participants
Bipolar Diagnosis Bipolar - I	72 Participants n=93 Participants	70 Participants n=4 Participants	142 Participants n=27 Participants
Bipolar Diagnosis Bipolar - II	68 Participants n=93 Participants	69 Participants n=4 Participants	137 Participants n=27 Participants
Rapid cycling course No	132 Participants n=93 Participants	134 Participants n=4 Participants	266 Participants n=27 Participants
Rapid cycling course Yes	8 Participants n=93 Participants	5 Participants n=4 Participants	13 Participants n=27 Participants
Duration of present depressive episode	12.3 Weeks STANDARD_DEVIATION 10.0 • n=93 Participants	13.7 Weeks STANDARD_DEVIATION 10.3 • n=4 Participants	13 Weeks STANDARD_DEVIATION 10.1 • n=27 Participants
Years since Bipolar diagnosis	3.2 Years STANDARD_DEVIATION 4.7 • n=93 Participants	2.8 Years STANDARD_DEVIATION 4.6 • n=4 Participants	3 Years STANDARD_DEVIATION 4.6 • n=27 Participants
Attempted sucide No	124 Participants n=93 Participants	128 Participants n=4 Participants	252 Participants n=27 Participants
Attempted sucide Yes	16 Participants n=93 Participants	11 Participants n=4 Participants	27 Participants n=27 Participants
Hamilton Rating Scale for Depression (HAM-D) total score at baseline	23.2 Scores on a scale STANDARD_DEVIATION 3.0 • n=93 Participants	23.5 Scores on a scale STANDARD_DEVIATION 3.6 • n=4 Participants	23.3 Scores on a scale STANDARD_DEVIATION 3.3 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: Full Analysis Set (Number of participants at Week 8: Placebo=100; Quetiapine XR=114)

MADRS total score range: 0 to 60, the higher the score, the more severe, Change : Total MADRS score at week 8 minus score at baseline

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Change From Baseline (Visit 2) to End of Study (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Change from Baseline to End of Study	-15.27 Scores on a scale Standard Error 0.81	-18.48 Scores on a scale Standard Error 0.78
Change From Baseline (Visit 2) to End of Study (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Baseline	28.8 Scores on a scale Standard Error 0.45	28.5 Scores on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: 8 weeks from baseline

Population: Full Analysis set

Montgomery-Asberg Depression Rating Scale (MADRS) total score range: 0 to 60, the higher the score, the more severe, Response was defined as ≥50% reduction in MADRS total score from baseline

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Response (Subjects With ≥50% Reduction From Baseline to Week 8 in MADRS Total Score)	62 Participants	93 Participants

SECONDARY outcome

Timeframe: After 8 week of start of treatment

Population: Full Analysis Set

Montgomery-Asberg Depression Rating Scale (MADRS) total score range: 0 to 60, the higher the score, the more severe, Remission was defined as MADRS total score ≤12

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Remission (the Proportion of Subjects With a MADRS Total Score ≤ 12 at Week 8 Assessment)	59 Participants	88 Participants

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full Analysis Set (Number of participants at each assessment : Baseline (Placebo=140, Quetiapine XR= 139), Week 1 (Placebo=140, Quetiapine XR= 139), Week 2 (Placebo=127, Quetiapine XR= 128), Week 4 (Placebo=114, Quetiapine XR= 120), Week 6 (Placebo=102, Quetiapine XR= 114), Week 8 (Placebo=100, Quetiapine XR= 114)).

MADRS total score range: 0 to 60, the higher the score, the more severe.

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Change From Baseline to Each Assessment in MADRS Total Score Change from Baseline to Week 1	-4.14 Scores on a scale Standard Error 0.50	-5.62 Scores on a scale Standard Error 0.51
Change From Baseline to Each Assessment in MADRS Total Score Change from Baseline to Week 2	-7.70 Scores on a scale Standard Error 0.64	-10.13 Scores on a scale Standard Error 0.65
Change From Baseline to Each Assessment in MADRS Total Score Change from Baseline to Week 4	-11.05 Scores on a scale Standard Error 0.69	-14.18 Scores on a scale Standard Error 0.69
Change From Baseline to Each Assessment in MADRS Total Score Change from Baseline to Week 6	-13.96 Scores on a scale Standard Error 0.76	-16.04 Scores on a scale Standard Error 0.74
Change From Baseline to Each Assessment in MADRS Total Score Change from Baseline to Week 8	-15.27 Scores on a scale Standard Error 0.81	-18.48 Scores on a scale Standard Error 0.78
Change From Baseline to Each Assessment in MADRS Total Score Baseline	28.8 Scores on a scale Standard Error 0.45	28.5 Scores on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full Analysis Set (Number of Participants at Week 8: Placebo=100; Quetiapine XR=114).

HAM-D total score range: 0 to 53, the higher the score, the more severe. Change : Total HAM-D score at week 8 minus score at baseline

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Change From Baseline to Week 8 in HAM-D Total Scores Change from Baseline to Week 8	-12.92 Scores on a scale Standard Error 0.61	-15.16 Scores on a scale Standard Error 0.59
Change From Baseline to Week 8 in HAM-D Total Scores Baseline	23.2 Scores on a scale Standard Error 1.96	23.5 Scores on a scale Standard Error 1.87

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full Anlaysis Set (Number of Participants at Week 8: Placebo=100; Quetiapine XR=112)

CGI-BP severity of illness-Overall bipolar range = 1-7, the higher is the total score,the more severe is the disease. CGI-BP severity of illness-Depression range: 1-7, the higher is the total score, the more severe is the disease

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Change From Baseline to Week 8 Assessment in the Clinical Global Impression Bipolar - Severity (CGI-BP-S) CGI-BP-S score for Overall Bipolar (BP) Illness	-1.73 Scores on a scale Standard Error 0.12	-2.24 Scores on a scale Standard Error 0.12
Change From Baseline to Week 8 Assessment in the Clinical Global Impression Bipolar - Severity (CGI-BP-S) CGI-BP-S score of depression	-1.81 Scores on a scale Standard Error 0.13	-2.28 Scores on a scale Standard Error 0.13
Change From Baseline to Week 8 Assessment in the Clinical Global Impression Bipolar - Severity (CGI-BP-S) CGI-BP-S overall score Baseline	4.5 Scores on a scale Standard Error .065	4.6 Scores on a scale Standard Error .067
Change From Baseline to Week 8 Assessment in the Clinical Global Impression Bipolar - Severity (CGI-BP-S) CGI-BP-S score for depression Baseline	4.5 Scores on a scale Standard Error .065	4.6 Scores on a scale Standard Error .068

SECONDARY outcome

Timeframe: After 8 weeks of start of treatment

Population: Full Analysis Set

Clinical Global Impression - Bipolar - Change (CGI-BP-C) of "much" or "Very much" improved is defined as a change in CGI-BP overall bipolar illness score ≤ 2 where 1 = very much improved, 2 = much improved.

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
The Proportion of Patients at Week 8 With a Clinical Global Impression - Bipolar - Change (CGI-BP-C) of "Much" or "Very Much" Improved	65 Participants	91 Participants

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full Analysis Set (Number of Participants at Week 8: Placebo=100; Quetiapine XR=114)

MADRS item 10 (suicidal ideation) score range: 0 to 6, the higher the score, the more severe, Change: MADRS item 10 score at week 8 minus score at baseline

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Change From Baseline to Week 8 in Item 10 of Montgomery-Asberg Depression Rating Scale (MADRS) for Suicidal Ideation Change from Baseline to Week 8	-0.76 Scores on a scale Standard Error 0.06	-0.98 Scores on a scale Standard Error 0.06
Change From Baseline to Week 8 in Item 10 of Montgomery-Asberg Depression Rating Scale (MADRS) for Suicidal Ideation Baseline	1.2 Scores on a scale Standard Error .094	1.0 Scores on a scale Standard Error .083

SECONDARY outcome

Timeframe: After 8 weeks of start of treatment

Population: Full Analysis Set

The incidence of treatment-emergent mania is defined as ≥16 of YMRS total score on 2 consecutive assessments or at final assessment, YMRS total score range: 0-60, the higher is the total score the more severe is the disease.

Outcome measures

Measure	Placebo n=140 Participants Placebo matching Quetiapine XR.	Quetiapine XR n=139 Participants Quetiapine Fumarate (SEROQUEL) Extended Release Tablet administered orally, once daily in the evening.
Incidence of Treatment-emergent Mania (AE of Mania or Hypomania, Defined as Young Mania Rating Scale [YMRS] Score ≥16 on 2 Consecutive Assessments or Final Assessment)	4 Participants	1 Participants

Adverse Events

PLACEBO

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

QUETIAPINE XR

Serious events: 0 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO n=147 participants at risk	QUETIAPINE XR n=147 participants at risk
Infections and infestations PERITONITIS	0.68% 1/147 • Number of events 1 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	0.00% 0/147 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Psychiatric disorders BIPOLAR I DISORDER	0.68% 1/147 • Number of events 1 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	0.00% 0/147 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Psychiatric disorders INTENTIONAL SELF-INJURY	0.68% 1/147 • Number of events 1 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	0.00% 0/147 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.

Other adverse events

Measure	PLACEBO n=147 participants at risk	QUETIAPINE XR n=147 participants at risk
Gastrointestinal disorders CONSTIPATION	2.7% 4/147 • Number of events 5 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	11.6% 17/147 • Number of events 17 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Gastrointestinal disorders DRY MOUTH	4.8% 7/147 • Number of events 7 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	14.3% 21/147 • Number of events 22 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Gastrointestinal disorders NAUSEA	6.8% 10/147 • Number of events 10 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	2.0% 3/147 • Number of events 3 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
General disorders FATIGUE	1.4% 2/147 • Number of events 3 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	8.8% 13/147 • Number of events 14 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Infections and infestations NASOPHARYNGITIS	6.8% 10/147 • Number of events 10 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	2.0% 3/147 • Number of events 3 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Nervous system disorders DIZZINESS	10.9% 16/147 • Number of events 19 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	19.7% 29/147 • Number of events 30 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Nervous system disorders SOMNOLENCE	7.5% 11/147 • Number of events 11 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	24.5% 36/147 • Number of events 36 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.
Psychiatric disorders INSOMNIA	8.2% 12/147 • Number of events 14 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.	2.7% 4/147 • Number of events 4 Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatment.

Additional Information

Dhaval Desai (MSD, Seroquel)

AstraZeneca

Phone: +13028857643

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution and Principal Investigator shall not publish or present any such results until the earlier of (i) the date of the first Study results publication, or in case of a Multi-Centre Study the first Multi-Centre Results publication, authorized by AstraZeneca and (ii) the end of the eighteen (18) month period following the completion, or early termination, of the Study at all participating sites.
• Publication restrictions are in place

Restriction type: OTHER