Adult Bipolar Mania
This study has been completed.
Sponsor:
AstraZeneca
Collaborator:
Quintiles
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00931723
First received: June 29, 2009
Last updated: March 27, 2012
Last verified: March 2012
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Mania |
Drug: Quetiapine fumarate XR Drug: Lithium Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
MedlinePlus related topics:
Bipolar Disorder
Drug Information available for:
Formic acid
Lithium carbonate
Lithium citrate
Quetiapine
Quetiapine fumarate
U.S. FDA Resources
Further study details as provided by AstraZeneca:
Primary Outcome Measures:
- Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43) [ Time Frame: Change in YMRS total score from baseline to Day 43. ] [ Designated as safety issue: No ]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).
Secondary Outcome Measures:
- The Number of Patients With Clinically Significant Response. [ Time Frame: 43 days (from baseline to Day 43) ] [ Designated as safety issue: No ]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.
- Remission [ Time Frame: Days 8 to 43 ] [ Designated as safety issue: No ]
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).
- Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness) [ Time Frame: Change from baseline to Day 43. ] [ Designated as safety issue: No ]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 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase) [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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.
- Improvement of Overall Bipolar Illness [ Time Frame: Day 43. ] [ Designated as safety issue: No ]
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.
- Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Change from baseline to Day 43. ] [ Designated as safety issue: No ]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 in Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in PANSS Activation Subscale Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in PANSS Positive Subscale Score [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 1 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 2 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 3 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 4 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 5 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 6 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 7 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 8 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 9 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 10 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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 in Each YMRS Item Score No. 11 [ Time Frame: Change from baseline to Day 43 ] [ Designated as safety issue: No ]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.
| Enrollment: | 356 |
| Study Start Date: | June 2009 |
| Study Completion Date: | November 2010 |
| Primary Completion Date: | November 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Seroquel XR and Lithium
|
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.
Other Name: Seroquel XR
Drug: 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 Comparator: 2
Seroquel XR and placebo
|
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.
Other Name: Seroquel XR
Drug: Placebo
Oral treatment twice daily.
|
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931723
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| Belgium | |
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| Cedex, Belgium | |
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| Dendermonde, Belgium | |
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| Montignies-sur-sambre, Belgium | |
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| Overpelt, Belgium | |
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| Tournai, Belgium | |
| Bulgaria | |
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| Burgas, Bulgaria | |
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| Cedex, Bulgaria | |
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| Kazanlak, Bulgaria | |
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| Pazardjik, Bulgaria | |
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| Plovdiv, Bulgaria | |
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| Radnevo, Bulgaria | |
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| Sofia, Bulgaria | |
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| Berlin, BE, Germany | |
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| Koln, NW, Germany | |
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| Berlin, Germany | |
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| Cedex, Germany | |
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| Mannheim, Germany | |
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| Munchen, Germany | |
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| Nurnberg, Germany | |
| India | |
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| Visakhapatnam, Andh Prad, India | |
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| Ahmedabad, Gujarat, India | |
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| Bangalore, Karna, India | |
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| Mangalore, Karna, India | |
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| Manipal, Karna, India | |
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| Nashik, Mahara, India | |
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| Jaipur, Rajasthan, India | |
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| Kanpur, Uttar Prad, India | |
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| Cedex, India | |
| Israel | |
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| Bat Yam, Israel | |
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| Beer Ya'acov, Israel | |
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| Cedex, Israel | |
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| Haifa, Israel | |
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| Petach-tikva, Israel | |
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| Tel-hashomer, Israel | |
| Poland | |
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| Bydgoszcz, Poland | |
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| Cedex, Poland | |
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| Choroszcz, Poland | |
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| Gorlice, Poland | |
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| Katowice, Poland | |
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| Krakow, Poland | |
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| Lublin, Poland | |
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| Poznan, Poland | |
| Russian Federation | |
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| Arkhangelsk, Russian Federation | |
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| Cedex, Russian Federation | |
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| Chita, Russian Federation | |
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| Kazan, Russian Federation | |
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| Moscow, Russian Federation | |
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| Saratov, Russian Federation | |
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| St Petersburg, Russian Federation | |
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| St. Petersburg, Russian Federation | |
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| Voronezh, Russian Federation | |
| South Africa | |
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| Bloemfontein, Free State, South Africa | |
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| Vereeniging, Free State, South Africa | |
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| Worcester, W Cape, South Africa | |
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| Cape Town, South Africa | |
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| Cedex, South Africa | |
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| Johannesburg, South Africa | |
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| Port Elizabeth, South Africa | |
| Ukraine | |
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| Cedex, Ukraine | |
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| Dnipropetrovsk, Ukraine | |
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| Donetsk, Ukraine | |
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| Kharkov, Ukraine | |
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| Kiev, Ukraine | |
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| Odessa, Ukraine | |
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| Vinnitsia, Ukraine | |
Sponsors and Collaborators
AstraZeneca
Quintiles
Investigators
| Study Director: | Michael Castiglione | AstraZeneca |
| Principal Investigator: | Michel Bourin, Professeur | Neurobiologie de l'anxiété et de la dépression Faculté de Médecine |
More Information
No publications provided
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT00931723 History of Changes |
| Other Study ID Numbers: | D144AC00003 |
| Study First Received: | June 29, 2009 |
| Results First Received: | November 17, 2011 |
| Last Updated: | March 27, 2012 |
| Health Authority: | Belgium: Federal Agency for Medicinal Products and Health Products Bulgaria: Bulgarian Drug Agency Germany: Federal Institute for Drugs and Medical Devices India: Drugs Controller General of India Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: FSI Scientific Center of Expertise of Medical Application Russia: Ministry of Health of the Russian Federation South Africa: Medicines Control Council Ukraine: State Pharmacological Center - Ministry of Health |
Keywords provided by AstraZeneca:
|
Acute Mania Mania, Adults Seroquel Acute Mania in Adult Patients |
Additional relevant MeSH terms:
|
Bipolar Disorder Affective Disorders, Psychotic Mood Disorders Mental Disorders Lithium Quetiapine Lithium Carbonate Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants |
Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Psychotropic Drugs Antimanic Agents Antidepressive Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013