Adult Bipolar Mania

Acute Mania Clinical Trial

Official title:

An International, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase IV Study of the Safety and Efficacy of Lithium Versus Placebo as an Add on to SEROQUEL XR (Quetiapine Fumarate) in Adult Patients With Acute Mania

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00931723
• Other study ID #: D144AC00003
• Status: Completed
• Phase: Phase 4
• First received: June 29, 2009
• Last updated: March 27, 2012
• Start date: June 2009
• Est. completion date: November 2010

Study information

• Verified date: March 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyGermany: Federal Institute for Drugs and Medical DevicesIndia: Drugs Controller General of IndiaPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: FSI Scientific Center of Expertise of Medical ApplicationRussia: Ministry of Health of the Russian FederationSouth Africa: Medicines Control CouncilUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if lithium 600-1800 mg/day is effective when added to quetiapine fumarate extended release (quetiapine XR or SEROQUEL® XR) 400-800 mg/day in treating acute mania and if so, how it compares with placebo (a non-active capsule, like a sugar pill, that looks like lithium).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 356
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Provision of informed consent before any study procedures are performed.

• The patient must have a documented clinical diagnosis for bipolar I disorder, including recent episode manic or mixed, and being male of females age 18-65 years, inclusive.

• Patients may be outpatients or inpatients at enrollment visit, but all patients must be inpatients when randomized and remain inpatients until discharged at the discretion of the investigator.

Exclusion Criteria:

• The patient can not have had up to 8 mood episodes during the past 12 months and not been continuously hospitalized for acute bipolar for up to 3 weeks immediately before participating in the study.

• The patient can not have a past diagnosis of stroke or medically documented transient ischemic attacks (TIA) or a history of seizure disorder, except for febrile convulsions.

• The patient must not have received electroconvulsive treatment (ECT) within 90 days before participating in the study and in the doctors judgement pose a current suicidal or homicidal risk.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Mania

Intervention

Drug:
• Quetiapine fumarate XR
Oral treatment, once daily, Day 1 = 300 mg, Day 2 and thereafter 600 mg. Dose might be adjusted as from Day 3 by the discretion of the investigator.
• Lithium
Oral treatment, twice daily, Days 1 and 2 = 600 mg/day, Days 3-8 = 900 mg/day. Dose adjustment from day 9 to end of study will be at the discretion of the investigator.
• Placebo
Oral treatment twice daily.

Locations

Country	Name	City	State
Belgium	Research Site	Cedex
Belgium	Research Site	Dendermonde
Belgium	Research Site	Montignies-sur-sambre
Belgium	Research Site	Overpelt
Belgium	Research Site	Tournai
Bulgaria	Research Site	Burgas
Bulgaria	Research Site	Cedex
Bulgaria	Research Site	Kazanlak
Bulgaria	Research Site	Pazardjik
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Radnevo
Bulgaria	Research Site	Sofia
Germany	Research Site	Berlin	BE
Germany	Research Site	Berlin
Germany	Research Site	Cedex
Germany	Research Site	Koln	NW
Germany	Research Site	Mannheim
Germany	Research Site	Munchen
Germany	Research Site	Nurnberg
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Bangalore	Karna
India	Research Site	Cedex
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kanpur	Uttar Prad
India	Research Site	Mangalore	Karna
India	Research Site	Manipal	Karna
India	Research Site	Nashik	Mahara
India	Research Site	Visakhapatnam	Andh Prad
Israel	Research Site	Bat Yam
Israel	Research Site	Beer Ya'acov
Israel	Research Site	Cedex
Israel	Research Site	Haifa
Israel	Research Site	Petach-tikva
Israel	Research Site	Tel-hashomer
Poland	Research Site	Bydgoszcz
Poland	Research Site	Cedex
Poland	Research Site	Choroszcz
Poland	Research Site	Gorlice
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Cedex
Russian Federation	Research Site	Chita
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Voronezh
South Africa	Research Site	Bloemfontein	Free State
South Africa	Research Site	Cape Town
South Africa	Research Site	Cedex
South Africa	Research Site	Johannesburg
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Vereeniging	Free State
South Africa	Research Site	Worcester	W Cape
Ukraine	Research Site	Cedex
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Kharkov
Ukraine	Research Site	Kiev
Ukraine	Research Site	Odessa
Ukraine	Research Site	Vinnitsia

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Quintiles, Inc.

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Germany,  India,  Israel,  Poland,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)	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).	Change in YMRS total score from baseline to Day 43.	No
Secondary	The Number of Patients With Clinically Significant Response.	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.	43 days (from baseline to Day 43)	No
Secondary	Remission	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).	Days 8 to 43	No
Secondary	Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)	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.	Change from baseline to Day 43.	No
Secondary	Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)	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.	Change from baseline to Day 43	No
Secondary	Improvement of Overall Bipolar Illness	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.	Day 43.	No
Secondary	Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	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.	Change from baseline to Day 43.	No
Secondary	Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in PANSS Activation Subscale Score	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in PANSS Positive Subscale Score	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 1	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 2	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 3	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 4	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 5	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 6	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 7	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 8	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 9	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 10	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.	Change from baseline to Day 43	No
Secondary	Change From Baseline to Day 43 in Each YMRS Item Score No. 11	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.	Change from baseline to Day 43	No