Clinical trial NCT00672490: Quetiapine Fumarate (Seroquel) as Mono-Therapy or Adjunct to Lithium in the Treatment of Patients With Acute Mania in Bipolar Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Mania in Bipolar Disorder
Keywords: Acute Mania
Bipolar Disorder
Quetiapine Fumarate
Lithium
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-05-06
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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:

* 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.

Primary outcomes:
measure: Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 28)
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Change From Baseline in the Clinical Global Impressions for Bipolar Disorder Severity of Illness (CGI-BP-S) Score to Each Assessment (Day 28)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Each Assessment (Day 28)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Each Assessment(Day 28)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the Young Mania Rating Scale (YMRS) Item 4 Score to Each Assessment
timeFrame: Baseline and 4 weeks
measure: Response Rate (Number of Patients With Clinically Response)
timeFrame: From Baseline to 4 weeks
measure: Remission Rate (Number of Patients With Clinically Significant Remission)
timeFrame: From Baseline to 4 weeks
measure: Treatment of Agitation (Change From Baseline in the PANSS Activation Subscale Score to Day 28)
timeFrame: Baseline and 4 weeks
measure: Treatment of Aggression Risk (Change From Baseline in the PANSS Supplement Aggression Risk Subscale Score to Day 28)
timeFrame: Baseline and 4 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Baoding
country: China
facility: Research Site
state: Hebei
city: Shijiazhuang
country: China
facility: Research Site
state: Hebei
city: Daqing
country: China
facility: Research Site
state: Heilongjiang
city: Xinxiang
country: China
facility: Research Site
state: Henan
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Suzhou
country: China
facility: Research Site
state: Jiangsu
city: Shenyang
country: China
facility: Research Site
state: Liaoning
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Xijing
country: China
facility: Research Site
state: Shanxi
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Kuming
country: China
facility: Research Site
state: Yunnan
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Huzhou
country: China
facility: Research Site
state: Zhejiang
Study officials:
affiliation: Peking University 6th hospital
name: Zhang Hongyan, Prof.
role: PRINCIPAL_INVESTIGATOR
References: