Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine

Official Title: “The Assessment of the Safety, Efficacy, and Practicality of an Algorithm Including Amantadine, Metformin and Zonisamide for the Prevention of Olanzapine-Associated Weight Gain in Outpatients With Schizophrenia”

The goal of this study is to answer the following questions: - Whether treatment with amantadine, metformin or zonisamide can prevent or reverse the weight gain that is associated with olanzapine - Whether taking amantadine, metformin or zonisamide can help patients decrease or eliminate some of the changes in body that occur with weight gain - How weight gain associated with olanzapine can affect people - Whether treatment with amantadine, metformin or zonisamide can help eliminate weight gain associated with olanzapine and not interfere with the positive effects of olanzapine on functioning of people with schizophrenia and other diseases

Intervention(s) in this Clinical Trial

• Drug: olanzapine
  • 5-20 milligrams (mg), oral, daily for 22 weeks.
• Drug: amantadine
  • Amantadine, 100 milligrams (mg), oral, 1 twice a day (BID). Patients who gained greater than 3 kilograms (kg) will switch to metformin. Patients who gained greater than 3 kg after switching to metformin will be switched to zonisamide.
• Drug: metformin
  • Metformin, 500 mg, oral, twice a day (BID) for 2 weeks titrated to 500mg three times a day (TID) thereafter. Patients who gain greater than 3 kilograms (kg) will be switched to amantadine. Patients who gained greater than 3 kg after switching to amantadine will be switched to zonisamide.
• Drug: zonisamide
  • Zonisamide, 100-400mg, oral, daily.
• Behavioral: Wellness education
  • weight management

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Olanzapine
  • olanzapine plus behavioral information
• Experimental: Olanzapine + Amantadine
  • Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information
• Experimental: Olanzapine + Metformin
  • Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information

Primary Measures

• Change From Baseline to Endpoint in Weight
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes

Secondary Measures

• Mean Change From Baseline to Endpoint in Fasting Triglycerides
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Mean Change From Baseline to Endpoint in Fasting Glucose
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Mean Change From Baseline to Endpoint in Hemoglobin A1c
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S)
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No

Inclusion Criteria:

• You must have been diagnosed with schizophrenia or schizoaffective disorder
• You must be able to visit the doctor's office once every two weeks for three months, then once every four weeks for the next three months with a possible bi-weekly visit during the fifth month
• If you are currently taking a medication for schizophrenia or schizoaffective disorder, you have been taking it for at least 30 days without any changes
• If you are a female, you must have a negative pregnancy test and be using an effective method of contraception

Exclusion Criteria:

• You have a diagnosis of bipolar I disorder, diabetes, very high triglyceride level (fasting triglycerides greater than or equal to 500 mg/dL), recent heart attack, stroke, uncontrolled seizures, serious infection, unstable heart disease (such as ischemic heart disease or congestive heart failure), an uncorrected narrow angle glaucoma or human immunodeficiency virus (HIV)
• You have diseases of the intestinal tract, lungs, liver, kidney, nervous or endocrine systems, or blood
• You have a diagnosis of an eating disorder
• You have a history of Parkinson's Disease or any related disorders
• You are allergic to sulfa drugs or any of the medications involved in this study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

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) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00401973

Study ID Number: 10768

ClinicalTrials.gov Identifier: NCT00401973

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry