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

NCT00579280 | Completed Phase 4 Results

• 1 other identifier: AZ 1107
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 3

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.

Conditions

Bipolar Disorder; Panic Disorder; Generalized Anxiety Disorder

Keywords

Randomized; Double-Blind; Placebo-Controlled; Quetiapine; DivalproexSodiumER; Bipolar; Anxiety; Panic; GAD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the CGI-21 Anxiety

  The CGI-21 Anxiety is a 21-point clinician-rated global improvement for anxiety symptoms. Response range: -10 to +10. The higher the score the more improvement. At Baseline all patients have a score of "0" (zero), against which any subsequent improvements or deterioration is assessed. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANOVA. Outcomes showing scores above zero indicate that patients did better, i.e. showed improvement on this scale.

  8 weeks (using LOCF Repeated Measures ANOVA)

Secondary Outcomes (10)

• Change From Baseline on Patient Global Improvement Scale (PGI-21) for Anxiety Symptoms

  8 weeks

• Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores

  8 weeks

• Change From Baseline in Sheehan Panic Disorder Scale (SPS)

  8 weeks

• Change From Baseline on Montgomery Asberg Depression Rating Scale (MADRS)

  8 weeks

• Change From Baseline in Young Mania Rating Scale (YMRS)

  8 weeks

Study Arms (3)

Quetiapine SR

ACTIVE COMPARATOR

Quetiapine SR (Quetiapine Sustained Release)

Drug: quetiapine SR

Divalproex Sodium ER

ACTIVE COMPARATOR

Divalproex Sodium ER (Divalproex Sodium Extended Release)

Drug: divalproex sodium ER

Placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

quetiapine SR DRUG

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

Quetiapine SR

divalproex sodium ER DRUG

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

Divalproex Sodium ER

placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• University of South Florida: lead
• AstraZeneca: collaborator

Study Sites (3)

VA Palo Alto HCS & Stanford School of Medicine

Palo Alto, California, 94304, United States

Location

University of South Florida College of Medicine

Tampa, Florida, 33613, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Panic Disorder; Generalized Anxiety Disorder; Anxiety Disorders

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Limitations and Caveats

Study was limited to 8 weeks and to patients with bipolar disorder and comorbid panic disorder or generalized anxiety disorder.

Results Point of Contact

• Title: David V. Sheehan, MD, MBA
• Organization: University of South Florida College of Medicine

dsheehan@health.usf.edu

813-974-4544

Study Officials

• David Sheehan, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: December 24, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2012-07

Locations

US (3)