Quetiapine SR and Divalproex Sodium ER in the Treatment of Anxiety in Bipolar Disorder With Panic Disorder and/or GAD

NCT ID: NCT00579280

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2010-12-31

Brief Summary

The specific aim of this study is to evaluate the efficacy, tolerability, and safety of quetiapine SR monotherapy and divalproex sodium ER monotherapy in comparison to placebo in the treatment of ambulatory bipolar disorder with co-morbid lifetime panic disorder or generalized anxiety disorder and current at least moderately severe anxiety.

Detailed Description

This is a randomized, double-blind, placebo controlled, parallel-group, 8-week trial of quetiapine SR monotherapy compared to divalproex sodium ER monotherapy in outpatient subjects with a lifetime bipolar I, II, or not otherwsise specified (NOS) disorder, a lifetime panic or generalized anxiety disorder, and current diagnosis at least moderately severe anxiety symptoms. Approximately 180 subjects will be randomized to obtain 90 subjects who complete the 8-week trial (30 completers per treatment group). This calculation is based on drop out rates in a similar patient population carried out by this group of collaborators. Subjects will be randomized to quetiapine SR or divalproex sodium ER or placebo in a 1:1:1 ratio. No concomitant psychotropic medication will be allowed throughout the study except for prn lorazepam during the first two weeks for the management of affective and anxiety symptoms, prn zolpidem and zaleplon for the management of insomnia and benztropine for the management of extrapyramidal side effects (EPS). Throughout the study, psychiatric scales will be used to assess psychiatric symptoms and the presence of treatment-emergent adverse events will be monitored and recorded.

Conditions

Bipolar Disorder; Panic Disorder; Generalized Anxiety Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Quetiapine SR

Quetiapine SR (Quetiapine Sustained Release)

Group Type: ACTIVE_COMPARATOR

quetiapine SR

Intervention Type: DRUG

flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks

Divalproex Sodium ER

Divalproex Sodium ER (Divalproex Sodium Extended Release)

Group Type: ACTIVE_COMPARATOR

divalproex sodium ER

Intervention Type: DRUG

Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks

Placebo

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

Interventions

quetiapine SR

flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks

Intervention Type: DRUG

divalproex sodium ER

Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must be at least 18 years of age and not older than 65
• Subjects must have lifetime bipolar I, II, or not otherwise specified (NOS) disorder as defined by DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision) criteria
• Subjects must have lifetime panic disorder or generalized anxiety disorder (GAD) as defined by DSM-IV, criteria (except clause "does not occur exclusively during a mood disorder" of Criterion F for GAD)
• Subjects' bipolar symptoms must be no more than moderate in severity, defined as a CGI-BP< 4
• Subjects' anxiety symptoms must be at least moderate in severity, defined as a CGI-S > 4
• Subjects must not be receiving regular mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication for at least one week prior to baseline. Patients receiving fluoxetine or depot antipsychotics should be off these medications for at least four weeks prior to baseline
• Subjects or their legally authorized representative must sign the Informed Consent Document after the nature of the trial has been fully explained
• If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable effective method(s) of contraception (e.g., hormonal methods, barrier methods, intrauterine device) for at least one month prior to study entry and throughout the study

Exclusion Criteria

• Subjects who do not have lifetime bipolar disorder by DSM-IV-TR criteria
• Subjects who do not have lifetime panic disorder or generalized anxiety disorder by DSM-IV-TR criteria
• Subjects who are receiving treatment with an anti-manic or mood stabilizing medication (lithium, valproate, carbamazepine, or an antipsychotic), and in the investigators' judgment, require ongoing treatment with that medication
• Subjects whose bipolar symptoms are presently more than moderately severe (CGI-BP>5)
• Subjects whose anxiety symptoms are presently less than moderately severe (CGI-S<3)
• Subjects with clinically significant suicidal or homicidal ideation.
• Subjects with a current DSM-IV TR Axis I diagnosis of delirium, dementia, amnesia, or other cognitive disorders; a DSM-IV TR diagnosis of a substance dependence disorder within the past six months; a lifetime DSM-IV TR psychotic disorder (e.g., schizophrenia or schizoaffective disorder)
• Subjects with serious general medical illnesses including hepatic, renal, respiratory, cardiovascular, endocrine, neurological, or hematological disease as determined by the clinical judgment of the clinical investigator. Subjects with hypo-or hyperthyroidism unless stabilized on thyroid replacement > 3 months
• Subjects with a clinically significant abnormality in their pre-study physical exam, vital signs, EKG, or laboratory tests
• Subjects who are allergic to or who have demonstrated hypersensitivity or intolerance to either of the active study medications
• Women who are pregnant or nursing
• Subjects who have received an experimental drug or used an experimental device within 30 days
• Subjects who have a history of neuroleptic malignant syndrome
• A patient with diabetes mellitus (DM) fulfilling one of the following criteria:
• Unstable DM defined as enrollment glycosylated hemoglobin (HbAlc) >8.5%
• Admitted to hospital for treatment of DM or DM related illness within the past 12 weeks
• Not under physician care for DM
• Physician responsible for patient's DM care has not indicated that the patient's DM is controlled
• Physician responsible for patient's DM care has not approved the patient's participation in the study
• Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks before randomization. For thiazolidinediones (glitazones) this period should not be less than 8 weeks before randomization
• Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a patient with DM meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of South Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Sheehan, MD

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

VA Palo Alto HCS & Stanford School of Medicine

Palo Alto, California, United States

University of South Florida College of Medicine

Tampa, Florida, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

AZ 1107

Identifier Type: -

Identifier Source: org_study_id