Open-Label Study of Intramuscular Olanzapine Depot in Patients With Schizophrenia or Schizoaffective Disorder - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by (Responsible Party):	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00088465

Purpose

This is a long-term, open-label clinical study designed to enable longer-term treatment of patients completing other clinical studies with intramuscular olanzapine depot.

Key objectives of the study are to:

Determine how well intramuscular (IM) olanzapine depot works during long-term treatment,
Evaluate the safety and tolerability of IM olanzapine depot during long-term treatment,
Determine the blood levels of IM olanzapine depot in patients during long-term treatment

Condition	Intervention	Phase
Schizophrenic Disorders Schizoaffective Disorder	Drug: Intramuscular olanzapine depot	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label Study of Intramuscular Olanzapine Depot in Patients With Schizophrenia or Schizoaffective Disorder

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia

Drug Information available for: Olanzapine

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Number of Participants With Adverse Events (AE) [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
The list of serious adverse events (SAE) and other non-serious adverse events (AE) are in Adverse Events Section.
Number of Participants With Treatment-Emergent Abnormal High Prolactin at Any Time Post Baseline [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
Prolactin normal reference ranges for female: 2.0 - 29.0 nanograms per milliliter (ng/mL); male: 2.0 - 20.0 ng/mL. High value is defined as a change from a value less than or equal to the high limit at all baseline visits to a value greater than the high limit at any time after baseline.
Number of Participants With Treatment-Emergent Abnormal High Alanine Transaminase (ALT), High Aspartate Transaminase (AST), High Total Bilirubin at Any Time Post Baseline [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
High ALT is defined as a baseline value of <3 times the upper limit of normal (ULN) to ≥3 times the ULN at any time post baseline. High AST is defined as a baseline value of <5 times the ULN to ≥5 times the ULN at any time post baseline. High total bilirubin is defined as a baseline value of <2 times the ULN to ≥2 times the ULN at any time post baseline.
Number of Participants Having Normal Fasting Baseline Glucose Value With Treatment-Emergent High Fasting Glucose at Any Time Post Baseline [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
Normal to high fasting glucose ≤100 milligrams per deciliter (mg/dL) at baseline to ≥126 mg/dL any time post baseline.
Number of Participants Having Normal Fasting Baseline Lipid Value With Treatment-Emergent High Fasting Lipid at Any Time Post Baseline [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
Normal to high fasting total cholesterol ≤200 mg/dL at baseline to ≥240 mg/dL any time post baseline. Fasting triglycerides <150 mg/dL at baseline to ≥200 mg/dL and <500 mg/dL any time post baseline.
Change From Baseline in Weight at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: Yes ]
Mean change in weight from baseline to last observation carried forward (LOCF) endpoint.
Number of Participants With Potentially Clinically Significant (PCS) Weight Gain at Month 76 Endpoint [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
PCS weight gain is defined as a ≥7% increase in weight from baseline.
Number of Participants With Extrapyramidal Symptoms at Any Time [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
Extrapyramidal symptoms are defined as Simpson-Angus total score (SAS) >3 at any post-baseline visit; Barnes Akathisia Scale (BAS) global score ≥2 at any post-baseline visit; A score ≥3 for any of Abnormal Involuntary Movement Scale (AIMS) for items 1-7 or a score ≥2 for any two of these items. Score for SAS is 0-4 for each of the 10 questions, with 0=normal and 4=extreme. The possible total score for SAS is 0-40. Possible score for BAS is 0-5, with 0=absent and 5=sever. Score 0-4 for each item of AIMS, with 0 =none and 4= sever. Possible total score for items 1-7 is 0-28.

Secondary Outcome Measures:

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
Assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210.
Change From Baseline in PANSS Positive Scores at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
PANSS questions 1-7. Assesses positive symptoms associated with schizophrenia. 7 items make up the positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total positive subscale scores range from 7 to 49.
Change From Baseline in PANSS Negative Scores at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
PANSS questions 8-14. Assesses negative symptoms associated with schizophrenia. 7 items make up the negative scale (e.g. blunted affect, emotional withdrawal, poor rapport, and passive/apathetic social withdrawal). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total negative subscale scores range from 7 to 49.
Change From Baseline in PANSS General Psychopathology Subscales at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
PANSS General Psychopathology Subscale is the Remaining 16 PANSS questions or PANSS Question15 through Question 30. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 16 items is defined as the PANSS General Psychopathology Subscales. Possible score ranges from 16 to 112.
Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Scores at Month 72 Endpoint [ Time Frame: Baseline, up to 72 months ] [ Designated as safety issue: No ]
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Change From Baseline in the Heinrichs-Carpenter Quality of Life Scale (QLS) Total Score at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
Heinrich-Carpenter QLS is an interviewer-rated scale which measures the impact of negative symptoms on occupational, social, and psychological functioning in patients with schizophrenia or schizoaffective disorder. Each of 21 items is rated on a scale from 0 (severely impaired functioning) to 6 (normal or adequate functioning), for a total score range of 0-126. Results are presented as change in Total score.
Change From Baseline in 36-Item Short Form Health Survey (SF-36) at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains.
Number of Psychiatric Visits [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: No ]
Psychiatric visits were outpatient visits to a psychiatrist or psychiatric nurse.
Days of Hospitalization [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: No ]
This is the total number of days for all hospitalized patients that were admitted to General, Psychiatric Ward as well as Intensive Care Unit (ICU).
Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) at Month 76 Endpoint [ Time Frame: Baseline, up to 76 months ] [ Designated as safety issue: No ]
The Subjective Well-Being under Neuroleptic Treatment-Short Form (SWN-S) is a patient self-rated scale developed to measure the subjective well-being for the previous 7 days of a patient under neuroleptic treatment. The SWN-S consists of 20 items (each item is rated from 1=not at all to 6=very much). Possible total score ranges from 20-120.
Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at Month 76 Endpoint [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: No ]
Self-rated scale that measures patient's level of satisfaction with current antipsychotic medication. Consists of 3 items assessing satisfaction with current study medication (scored from 1='very dissatisfied' to 5='very satisfied'), preference comparing current study medication versus previous medications (scored from 1='much prefer previous medication' to 5='much prefer study medication'), and side effects of current study medication compared with previous medications (scored from 1='much less side effects' to 5='much more side effects'). Range of possible scores is 3-15.
Plasma Olanzapine Concentrations in Participants During Long-Term Treatment by Year [ Time Frame: Randomization to end of study up to 76 months ] [ Designated as safety issue: Yes ]
Plasma olanzapine concentrations are expressed as (nanogram/milliliter)/(milligram/day) ([ng/mL]/[mg/day]).

Enrollment:	931
Study Start Date:	August 2004
Study Completion Date:	December 2010
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Intramuscular Olanzapine Depot Intramuscular (IM) olanzapine depot flexible dosing and flexible interval	Drug: Intramuscular olanzapine depot 45-405 milligram (mg), intramuscular injection, on a 2-, 3-, or 4-week interval. Other Names: LY170053 Zyprexa Adhera

Eligibility

Ages Eligible for Study:	18 Years to 76 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have schizophrenia
Female patients of childbearing potential must be using a medically accepted means of contraception
Patients must have completed (within 10 days) another IM olanzapine depot study if permitted by that study's protocol.

Exclusion Criteria:

Patients must not have participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) prior to study entry
Female patients must not be pregnant or breast-feeding
Patients must not be experiencing acute, serious or unstable medical conditions other than schizophrenia or schizoaffective disorder
Patients must not have a substance (except nicotine or caffeine) dependence within the past 30 days

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088465

Show 92 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director:

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Eli Lilly and Company

More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McDonnell DP, Detke HC, Bergstrom RF, Kothare P, Johnson J, Stickelmeyer M, Sanchez-Felix MV, Sorsaburu S, Mitchell MI. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010 Jun 10;10:45.

Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, Corya SA. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010 Jun 10;10:43.

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00088465 History of Changes
Other Study ID Numbers:	5995, F1D-MC-HGKB
Study First Received:	July 26, 2004
Results First Received:	October 14, 2011
Last Updated:	December 9, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Olanzapine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents

Therapeutic Uses
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 09, 2012