Acute Mania in Bipolar DisorderPhase 4MANIANCT00672490
Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder
A Phase 4 study testing Quetiapine Fumarate and Lithium in people with Acute Mania in Bipolar Disorder, run by AstraZeneca at 16 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Acute Mania in Bipolar Disorder
- What is being tested?
- Quetiapine Fumarate and Lithium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 376 participants
- Where
- 16 sitesChina
- Study dates
- Apr 2008to Jul 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 29Show fewer
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
China16 sites
Research Site
Baoding, Hebei
Research Site
Beijing, Beijing Municipality
Research Site
Chengdu, Sichuan
Research Site
Daqing, Heilongjiang
Research Site
Guangzhou, Guangdong
Research Site
Hangzhou, Zhejiang
Research Site
Huzhou, Zhejiang
Research Site
Kuming, Yunnan
Research Site
Shanghai, Shanghai Municipality
Research Site
Shenyang, Liaoning
Research Site
Shijiazhuang, Hebei
Research Site
Suzhou, Jiangsu
Research Site
Tianjin, Tianjin Municipality
Research Site
Wuhan, Hubei
Research Site
Xijing, Shanxi
Research Site
Xinxiang, Henan
About this study
Official title: An Open Label, 4-Week, Randomised, Multi-Centre, Phase IV Study to Compare the Efficacy and Safety of Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder
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
- Conditions
- Acute Mania in Bipolar Disorder
- Being tested
- Quetiapine Fumarate, Lithium
- Keywords
- Acute Mania, Bipolar Disorder, Quetiapine Fumarate, Lithium
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quetiapine FumarateDrug
Also called Seroquel
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
LithiumDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Quetiapine Fumarate - tablets Receives: Drug: Quetiapine Fumarate |
| 2 | Experimental | Quetiapine Fumarate - tablets and Lithium Receives: Drug: Quetiapine Fumarate; Drug: Lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 4 weeks
Secondary outcomes (8)
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
Measured: Baseline and 4 weeks
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
Measured: Baseline and 4 weeks
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.
Measured: Baseline and 4 weeks
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.
Measured: Baseline and 4 weeks
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.
Measured: From Baseline to 4 weeks
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.
Measured: From Baseline to 4 weeks
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.
Measured: Baseline and 4 weeks
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.
Measured: Baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startApr 2008
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Mania in Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 376 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zhang Hongyan, Prof., Principal investigator, Peking University 6th hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672490
- Sponsor's protocol ID
- D1443L00023
- Acronym
- MANIA
- Status last verified
- Jun 2012
- First submitted
- 2 May 2008
- Last updated
- 12 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, 4-Week, Randomised, Multi-Centre, Phase IV Study to Compare the Efficacy and Safety of Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder
- ClinicalTrials.gov ID
- NCT00672490
- Acronym / sponsor ID
- MANIA / D1443L00023
- Conditions
- Acute Mania in Bipolar Disorder
- Keywords
- Acute Mania, Bipolar Disorder, Quetiapine Fumarate, Lithium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 376 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 6 May 2008 (estimated)
- Results
- Posted 12 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Quetiapine FumarateQuetiapine Fumarate - tablets |
| 2 | Experimental | Drug: Quetiapine Fumarate, Drug: LithiumQuetiapine Fumarate - tablets and Lithium |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quetiapine FumarateAlso: SeroquelOral 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 | Drug | 1, 2 |
| LithiumOral treatment, twice daily. 250 mg/day to 2000mg/day from Day1 to Day 7, 500mg/day to 2000mg/day thereafter, judged by the investigator. | Drug | 2 |
Primary outcome
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)
Time frame: Baseline and 4 weeks
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).
8 secondary outcomes
Change From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)
Time frame: Baseline and 4 weeks
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)
Time frame: Baseline and 4 weeks
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)
Time frame: Baseline and 4 weeks
Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment
Time frame: Baseline and 4 weeks
Response Rate (Number of Patients With Clinically Response)
Time frame: From Baseline to 4 weeks
Remission Rate (Number of Patients With Clinically Significant Remission)
Time frame: From Baseline to 4 weeks
Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)
Time frame: Baseline and 4 weeks
Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)
Time frame: Baseline and 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhang Hongyan, Prof. principal investigator
Peking University 6th hospital
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Quetiapine Fumarate and Lithium in people with Acute Mania in Bipolar Disorder, run by AstraZeneca at 16 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28) (time frame: Baseline and 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2012.