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CompletedNCT00672490MANIAUpdated Jul 12, 2012Results posted

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

A Phase 4 interventional study of Quetiapine Fumarate and Lithium in Acute Mania in Bipolar Disorder, sponsored by AstraZeneca. Completed at 16 sites in China. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2012-07-12.

Sponsored by AstraZeneca · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
376
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study summary

To compare the efficacy and safety of quetiapine fumarate given as mono-therapy or adjunct therapy to lithium in the treatment of patients with acute mania in bipolar disorder. Patients with a documented clinical diagnosis of bipolar mania according to DSM-IV criteria (296.4X Bipolar I Disorder, Most Recent Episode Manic; 296.0X Bipolar I Disorder, Single Manic Episode) are required to have a YMRS total score of ≥20 at enrolment and randomisation

02

Conditions studied

  • Acute Mania in Bipolar Disorder

Keywords

  • Acute Mania
  • Bipolar Disorder
  • Quetiapine Fumarate
  • Lithium
03

In context

Mania

97 studies on the registry are indexed under Mania; 10 are open to participants now.

This study's enrollment of 376 is above the median of 86 across 86 interventional studies indexed under Mania.

Browse Mania studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Provision of written informed consent before initiation of any study related procedures. Patients who are deemed incapable of providing informed consent maybe enrolled if written informed consent has been obtained from the patient's Legally Authorized Representative.
  • Documented clinical diagnosis meeting the DSM-IV criteria for any of the following:
  • 296.4X Bipolar I Disorder, Most Recent Episode Manic
  • 296.0X Bipolar I Disorder, Single Manic Episode
  • Have a YMRS score of at least 20 and a score of at least 4 on 2 of the following 4 YMRS items both at enrolment and at randomisation: Irritability, Speech, Content, and Disruptive/Aggressive Behaviour.
  • Female patients of childbearing potential must have a negative urine pregnancy test at enrolment and be willing to use a reliable method of birth control, i.e., barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation, during the study.
  • Be able to understand and comply with the requirements of the study, as judged by the investigator.

Exclusion criteria

Exclusion Criteria:

  • Manic episode judged to be either:
  • the direct physiological consequence of a treatment or medical condition other than Bipolar disorder.
  • the direct physiological effect of a substance of abuse; intoxication with hallucinogens, inhalants, opioids, or phencyclidine and related substances.
  • the direct physiological effect of psychostimulant or antidepressant medication.
  • Evidence of clinically severe or active disease, or a clinical finding that is unstable or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication.
  • History of seizure disorder, except febrile convulsions.
  • Hospitalization period of 3 weeks or longer immediately prior to randomization for the index manic episode.
  • Known history of intolerance or hypersensitivity to quetiapine or lithium, or to any other component in the tablets/capsules.
  • Known lack of response to quetiapine or lithium, as judged by the investigator.
  • Use of antipsychotic medication or mood stabilizer other than quetiapine and lithium at the day of randomisation (to be tapered to discontinuation between the enrolment visit and randomisation).
  • Administration of a depot antipsychotic injection within 1 dosing interval (for the depot) before randomisation.
  • Use of clozapine within 28 days prior to randomisation.
  • Use of antidepressants during the enrolment period or within a period of 5 half-lives of the drug(s) prior to randomisation.
  • Continuous daily use of benzodiazepines in excess of 4 mg per day of lorazepam, or the equivalent, during 28 days prior to randomisation.
  • Use of drugs that induce or inhibit the hepatic metabolizing cytochrome 3A4 enzymes within 14 days before randomisation.
  • Receipt of electroconvulsive therapy (ECT) within 28 days prior to randomisation.
  • Clinically significant deviation from the reference range in clinical laboratory test results at enrolment, as judged by the investigator.
  • An absolute neutrophil count (ANC) of \<1.5X109/L.
  • Treatment with quetiapine with a dosage of at least 50 mg/day at enrolment (Visit 1)
  • Liver function test AST or ALT 2 times as the upper normal limit.
  • A thyroid-stimulating hormone (TSH) concentration more than 10% above the upper limit of the normal range of the laboratory used for sample analysis at enrolment, whether or not the subject is being treated for hypothyroidism.
  • Known diagnosis of Diabetes Mellitus (DM) or fasting blood glucose level > the upper normal limit.
  • Risk of transmitting human immuno-deficiency virus (HIV) or hepatitis B via blood or other body fluids, as judged by the investigator.
  • ECG results considered to be clinically significant as determined by the investigator.
  • Conditions that could affect absorption and metabolism of study medication.
  • Patients who in the investigators opinion will require systematic psychotherapy (other than supportive psychotherapy) during the study period.
  • Participation in another clinical study or compassionate use programme within 28 days prior to randomisation, or longer if locally required.
  • Involvement in the planning and conduct of the study (applies to all AstraZeneca or staff at the investigational site).
  • Previous enrolment or randomisation of treatment in the present study.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
376 participants (actual)

Study arms

  • Experimental
    1

    Quetiapine Fumarate - tablets

    Drug: Quetiapine Fumarate

  • Experimental
    2

    Quetiapine Fumarate - tablets and Lithium

    Drug: Quetiapine Fumarate · Drug: Lithium

Interventions

  • DrugQuetiapine Fumarate

    Oral treatment, twice daily. 100 mg/day at Day 1, 200 mg/day at Day 2, 300 mg/day at Day 3, 400 mg/day at Day 4, from 400 mg/day to 600 mg/day before Day 8, from 600 mg/day to 800 thereafter, judged by the investigator. Tablets

    Also known as: Seroquel

  • DrugLithium

    Oral treatment, twice daily. 250 mg/day to 2000mg/day from Day1 to Day 7, 500mg/day to 2000mg/day thereafter, judged by the investigator.

06

What researchers measure

Primary outcomes

  1. Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)

    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).

    Time frame: Baseline and 4 weeks

Secondary outcomes

  1. Change From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)

    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

    Time frame: Baseline and 4 weeks

  2. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)

    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 total score is the sum of all 30 individual-item scores and ranges from 30 to 210

    Time frame: Baseline and 4 weeks

  3. Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)

    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.

    Time frame: Baseline and 4 weeks

  4. Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment

    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.

    Time frame: Baseline and 4 weeks

  5. Response Rate (Number of Patients With Clinically Response)

    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.

    Time frame: From Baseline to 4 weeks

  6. Remission Rate (Number of Patients With Clinically Significant Remission)

    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.

    Time frame: From Baseline to 4 weeks

  7. Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)

    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.

    Time frame: Baseline and 4 weeks

  8. Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)

    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.

    Time frame: Baseline and 4 weeks

07

Results

Posted Jul 12, 2012

Participant flow

Participant flow — Overall Study
MilestoneQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Started187189
Completed163157
Not completed2432
Withdrew: Withdrawal by subject88
Withdrew: Lack of compliance27
Withdrew: Mismatch include/exclude criteria10
Withdrew: Adverse event58
Withdrew: Violation of concomitant medicine10
Withdrew: Intolerance02
Withdrew: Lost to follow-up15
Withdrew: No reason was provided62

Outcome measures

PrimaryChange in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)

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).

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)-25.7 ± 13.7-26.1 ± 13.4
SecondaryChange From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)

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

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Change From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
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 ± 0.115-0.17 ± 0.144
SecondaryChange From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)

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 total score is the sum of all 30 individual-item scores and ranges from 30 to 210

Time frame:
Baseline and 4 weeks
Reported as:
Mean · units on a scale
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)
units on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)-16.12 ± 0.285-16.44 ± 0.28
SecondaryChange From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)

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.

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)-2.99 ± 0.181-3.02 ± 0.179
SecondaryChange From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment

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.

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment-2.0 ± 1.2-2.1 ± 1.2
SecondaryResponse Rate (Number of Patients With Clinically Response)

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.

Time frame:
From Baseline to 4 weeks
Reported as:
Number · Participants
Response Rate (Number of Patients With Clinically Response)
ParticipantsQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Response Rate (Number of Patients With Clinically Response)139153
SecondaryRemission Rate (Number of Patients With Clinically Significant Remission)

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.

Time frame:
From Baseline to 4 weeks
Reported as:
Number · Participants
Remission Rate (Number of Patients With Clinically Significant Remission)
ParticipantsQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Remission Rate (Number of Patients With Clinically Significant Remission)117123
SecondaryTreatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)

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.

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)-5.4 ± 4.5-5.8 ± 4.2
SecondaryTreatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)

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.

Time frame:
Baseline and 4 weeks
Reported as:
Mean · score on a scale
Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)
score on a scaleQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)-6.8 ± 5.1-7.3 ± 5.1

Adverse events

Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Quetiapine Fumarate Used as Mono-Therapy—0/187 (0%)120/187 (64.2%)
Quetiapine Fumarate Used as Adjunct Therapy—1/189 (0.5%)125/189 (66.1%)
Most frequent serious events
Most frequent serious events
EventQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
InjuryMusculoskeletal and connective tissue disorders0/1871/189
Most frequent other events
Showing 10 of 18
Most frequent other events
EventQuetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct Therapy
ConstipationGastrointestinal disorders13/18724/189
DizzinessNervous system disorders21/18714/189
Weight IncreasedInvestigations12/18716/189
NauseaGastrointestinal disorders4/18715/189
Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders14/18712/189
HypersomniaNervous system disorders13/1879/189
TremorNervous system disorders5/18713/189
Extrapyramidal SymptomNervous system disorders6/18712/189
TachycardiaCardiac disorders11/1877/189
SomnolenceNervous system disorders10/18710/189

Baseline characteristics

Age Continuous
Age Continuous(years)Quetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct TherapyTotal
Mean34.3 ± 12.1632.43 ± 11.1433.36 ± 11.68
Sex: Female, Male
Sex: Female, Male(Participants)Quetiapine Fumarate Used as Mono-TherapyQuetiapine Fumarate Used as Adjunct TherapyTotal
Female9487181
Male93102195
08

Study locations

16 sites
  • Research Site
    Beijing, Beijing, China
  • Research Site
    Guangzhou, Guangdong, China
  • Research Site
    Baoding, Hebei, China
  • Research Site
    Shijiazhuang, Hebei, China
  • Research Site
    Daqing, Heilongjiang, China
  • Research Site
    Xinxiang, Henan, China
  • Research Site
    Wuhan, Hubei, China
  • Research Site
    Suzhou, Jiangsu, China
  • Research Site
    Shenyang, Liaoning, China
  • Research Site
    Shanghai, Shanghai, China
  • Research Site
    Xijing, Shanxi, China
  • Research Site
    Chengdu, Sichuan, China
  • Research Site
    Tianjin, Tianjin, China
  • Research Site
    Kuming, Yunnan, China
  • Research Site
    Hangzhou, Zhejiang, China
  • Research Site
    Huzhou, Zhejiang, China
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 12, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00672490
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
May 6, 2008
Start date
Apr 2008
Primary completion
Jul 2009
Completion
Jul 2009
Results posted
Jul 12, 2012
Last update
Jul 12, 2012

Study contacts

Zhang Hongyan, Prof.
principal investigator · Peking University 6th hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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