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
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: Olanzapine/Zyprexa
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind Placebo-Controlled Olanzapine Add-on Therapy in the Treatment of Acute Syndromal and Subsyndromal Exacerbations in Bipolar Disorders

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • CGI-S [ Time Frame: prior week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 50
Study Start Date: July 2005
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olanzapine/Zyprexa
Olanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week
Drug: Olanzapine/Zyprexa
Placebo Comparator: Placebo
Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00186017

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Eli Lilly and Company
Investigators
Principal Investigator: Terence Arthur Ketter Stanford University
  More Information

Additional Information:
No publications provided

Responsible Party: Terrence Ketter, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00186017     History of Changes
Other Study ID Numbers: 79897, F1D-US-X279
Study First Received: September 12, 2005
Last Updated: December 11, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Pathologic Processes
Olanzapine
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 21, 2014