Subcutaneous Olanzapine for Hyperactive or Mixed Delirium

Study of Subcutaneous Olanzapine for Hyperactive or Mixed Delirium

The objective of this study is to determine the tolerability and safety of olanzapine administered as a subcutaneous injection to hospitalized patients with hyperactive or mixed delirium.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Olanzapine

Detailed Description

Olanzapine is a drug designed to control agitation/delirium. Olanzapine has been given by mouth and as an injection into the muscle, which is painful and can increase a person's feelings of agitation. In this study, olanzapine will be given under the skin through a catheter. Researchers hope that this will be less painful and agitating than when injected into the muscle.

If you are found to be eligible to take part in this study, you will have a catheter (plastic tube) placed under your skin. This catheter will be used to give you the study medication. Study drug will be given through the catheter every 8 hours for 9 doses. Each shot should take about 1 to 2 minutes. You will receive the drug at M.D.Anderson Cancer Center.

Researchers will use the Richmond Agitation Scale to measure your agitation or sedation before each injection of olanzapine through the catheter. It should take 5 to 10 minutes to answer the questions. You will be evaluated for catheter site reaction at the time of injection, at 30 minutes and 1 hour after the injection, and before all further injections of study drug. Your blood pressure will be evaluated before and 1 hour after the first two injections and then once a day while on study.

If your agitation is not controlled, you will receive haloperidol. On the second day of treatment, researchers will record the amount of haloperidol that you had to use in the previous 24 hours. If the amount of haloperidol that you used is greater than a certain amount, your dose of olanzapine will be increased. Even if your dose of olanzapine is increased, you may still be able to use haloperidol if needed.

On the third day of treatment, researchers will record the amount of haloperidol that you had to use in the previous 24 hours. If the amount of haloperidol that you used is greater than a certain amount, your dose of olanzapine will again be increased. As before, if your dose of olanzapine is increased, you may still be able to use haloperidol if needed. If you respond to olanzapine after 3 days of treatment, you will be given the option to continue the drug off-study.

If you develop severe side effects before you have completed the 9 doses, treatment will be stopped. If treatment on this study is stopped, then you will consult with your doctor about receiving a different medication off study to help control your symptoms. There is no long-term follow-up for this study.

This is an investigational study. Olanzapine has been FDA approved given into the muscle or by mouth for the treatment of agitation related to schizophrenia and bipolar mania (a disorder involving mood swings from deep depression to feelings of elation). A total of 25 patients will take part in this study. All will be enrolled at M.D. Anderson.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • U.T.M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hospitalized patients on the Acute Palliative Care Unit (G12NW) at the University of Texas MD Anderson Cancer Center
2. Age > 18 years of age (Olanzapine IM has not been evaluated in pediatric patients.)
3. Patients must have an acceptable surrogate capable of giving consent on the subject's behalf.
4. Richmond Agitation-Sedation Score (RASS) of >/= 1
5. Mini Mental Status Exam score of less than 24
6. Hyperactive or mixed delirium not responsive to at least 10 mg of haloperidol within the last 24 hours

Exclusion Criteria:

1. Known hypersensitivity to any ingredient of olanzapine IM
2. The following reactions to haloperidol: A) Acute dystonia B) Hypersensitivity or previous intolerance to haloperidol C) Extra pyramidal side effects
3. History of narrow-angle glaucoma.
4. Systolic blood pressure < 90 mm Hg
5. If they received an injectable depot neuroleptic within less than one dosing interval of study initiation
6. Within 7 days of starting study drug, documentation of: a. Fasting blood glucose (or finger stick glucose check) > 250 mg/dl b. Absolute neutrophil count of < 500 or platelets < 50,000
7. The use of any benzodiazepines or neuroleptic medications, besides haloperidol, while the patient is enrolled on study, is prohibited.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olanzapine; 5 mg subcutaneous injection every 8 hours for 9 doses	Drug: Olanzapine; 5 mg subcutaneous injection every 8 hours for 9 doses. Each injection should take about 1 to 2 minutes.; Other Names: Symbyax; Fluoxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Toxicity	Toxicity defined as urticaria, injection site reactions, and/or hypotension. At time 0, 0.5, and 1 hour after the first injection of study drug and prior to all subsequent injections of study drug, urticaria and injection site reaction assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. Blood pressure evaluated immediately before and 1 hour after each of the first 2 injections, and then daily thereafter.	Within 75 hours of the initial treatment
Participant Hypotension	Participants who experience a drop in blood pressure below 90/50 mm Hg within 60 minutes post study drug administration. Blood pressure evaluated immediately before and 1 hour after each of the first 2 injections, and then daily thereafter.	3 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Richmond Agitation Sedation Scale (RASS)	Evaluation of RASS at time 0, once the injection is completed, at 0.5 hours post-injection, and at 1 hour post-injection for the first injection of study drug, and then prior to each injection of study drug to determine efficacy. Treatment efficacy defined as: RASS Score of less than 1 prior to the last dose on the third day; and Total haloperidol usage of less than 8 mg per day. Haloperidol amounts recorded for previous 24 hours.	3 Days

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Ahmed Elsayem, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• UT MD Anderson Cancer Center official website

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 6, 2007
• First Posted (Estimate): August 7, 2007

Study Record Updates

• Last Update Posted (Estimate): September 27, 2011
• Last Update Submitted That Met QC Criteria: September 26, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Advanced Cancer; Olanzapine; Hyperactive Delirium; Mixed Delirium
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Dyskinesias; Delirium; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Olanzapine; Fluoxetine
• Other Study ID Numbers: 2004-0746

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No