Short Term Rescue Study of Olanzapine

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Terrence Ketter, Stanford University
ClinicalTrials.gov Identifier:
NCT00186017
First received: September 12, 2005
Last updated: December 11, 2012
Last verified: December 2012

September 12, 2005
December 11, 2012
July 2005
June 2010   (final data collection date for primary outcome measure)
CGI-S [ Time Frame: prior week ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00186017 on ClinicalTrials.gov Archive Site
  • YMRS [ Time Frame: prior week ] [ Designated as safety issue: Yes ]
  • Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS) [ Time Frame: Prior week ] [ Designated as safety issue: No ]
  • Hamilton Anxiety Rating Scales (HARS) [ Time Frame: Prior week ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Short Term Rescue Study of Olanzapine
Double-Blind Placebo-Controlled Olanzapine Add-on Therapy in the Treatment of Acute Syndromal and Subsyndromal Exacerbations in Bipolar Disorders

We will assess the effect of olanzapine compared to placebo added to prior treatment on CGI-S in a one-week randomized double-blind study. We will also assess the effect of olanzapine added to prior treatment on CGI-S in an eight-week open treatment study. In addition, we will assess the effect of olanzapine on Young Mania Rating Scale (YMRS), Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS), and Hamilton Anxiety Rating Scales (HARS) in the above paradigms. We will also assess the influence of presentation severity (CGI-S) and polarity (mood elevation versus depression) on olanzapine response. Finally, we will assess safety and tolerability of olanzapine in the above paradigms.

We hypothesize that in diverse mild syndromal and subsyndromal exacerbations of BD in outpatients, randomized double-blind flexibly dosed olanzapine added to prior treatment (including no treatment) will yield greater CGI-S improvement than placebo by the end of one week, and that such improvement will persist over one week of open continuation treatment.

Development and marketing of new therapies for bipolar disorders (BD) has typically entailed performing double-blind placebo-controlled trials in acute mania 1, 2, maintenance studies 3, 4, and more recently acute depression studies 5. Such an approach addresses BD primarily in terms of episodes and has the strength of studying levels of pathology sufficiently high to permit detection of treatment effects, and guiding clinicians when they encounter syndromal mood episodes. However, this approach has the important limitation of not addressing an important unmet clinical need, namely the management of subsyndromal symptoms. Indeed, emerging data suggest that in BD subsyndromal symptoms compared to syndromal episodes are far more pervasive 6, 7. Also such an approach runs the risk of not paying sufficient attention to the disorder construct, in a sense permitting preoccupation with syndromal episodes to carry more importance than the disorder.

Our group has published a novel open study of olanzapine in diverse exacerbations of BD 8. Twenty-five bipolar disorder [14 bipolar I (BPI), 10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)] outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal, eight subsyndromal) mood symptoms of at least mild severity, with Clinical Global Impression-Severity (CGI-S) scores of at least 3. Only one had psychotic symptoms. With open olanzapine (15 adjunctive, 10 monotherapy), overall symptom severity (CGI-S) as well as mood elevation (Young Mania Rating Scale), depression (Hamilton and Montgomery-Asberg Depression Rating Scales), and anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by days 2-3). Patients with the greatest baseline severity (CGI-S) had the greatest improvement. Fifteen of 25 (60%) patients responded. Time to consistent response was bimodal, with five early (by 0.5 +/- 0.3 weeks) and 10 late (by 7.0 +/- 1.9 weeks) responders. Early compared with late responders had 51% lower final olanzapine doses. Olanzapine was generally well tolerated, with sedation and weight gain the most common adverse effects. Thus, olanzapine appeared effective in diverse exacerbations of BD in outpatients. Controlled studies are warranted to further explore these preliminary observations.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Bipolar Disorder
Drug: Olanzapine/Zyprexa
  • Experimental: Olanzapine/Zyprexa
    Olanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week
    Intervention: Drug: Olanzapine/Zyprexa
  • Placebo Comparator: Placebo
    Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
June 2010
June 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:Patients must meet the following criteria to be eligible to participate in the study:

  • Male or female outpatients, 18 to 70 years of age
  • Female patients of childbearing potential must be using a medically accepted means of contraception
  • Able to communicate intelligently with the investigator, and study coordinator
  • Able to give informed consent
  • DSM-IV diagnosis of bipolar I, bipolar II, cyclothymic disorder or bipolar disorder not otherwise specified, experiencing an acute exacerbation of their illness at Visit 1 (hypomania, subsyndromal depression, hypomania and subsyndromal depression, depression and hypomania, or depression if diagnosed with bipolar II) as verified by SCID-I/P
  • CGI-BP Overall Severity score greater than or equal to mildly ill at Visit 1
  • Must have been on prior medications for at least 2 weeks (6 weeks for fluoxetine) immediately prior to study entry

Exclusion Criteria:Patients may not participate in the study if they have any of the following conditions:

  • Pregnant, nursing, or intending to become pregnant during the study
  • Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease such that hospitalization for the disease is anticipated within 3 months or death is anticipated within 3 years.
  • A history of seizure disorder
  • History of leukopenia without a clear and resolved etiology.
  • DSM-IV substance (except nicotine or caffeine) dependence within the past month
  • Judged clinically to be at serious suicidal risk
  • Participation in clinical trial of another investigational drug within 1 month (30 days) prior to study entry.
  • Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to study entry
  • Treatment resistance, non-response, or intolerability with olanzapine by the investigator's judgment
  • Treatment with clozapine within 3 months prior to study entry
  • Treatment with remoxipride within 6 months (180 days) prior to study entry
  • Treatment with an oral antipsychotic within 2 days prior to study entry
  • A course of ECT (electroconvulsive therapy) in the preceding 4 weeks
  • Excluded mood symptoms noted in Table 1 [of protocol]
  • Unstable thyroid pathology and treatment-initiated or altered within the past 3 months
  • Meet criteria for antisocial personality disorder
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00186017
79897, F1D-US-X279
No
Terrence Ketter, Stanford University
Stanford University
Eli Lilly and Company
Principal Investigator: Terence Arthur Ketter Stanford University
Stanford University
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP