Comparing the Effect of Under the Tongue Olanzapine Versus Swallowed Olanzapine on Body Mass Index (A Ratio of Weight to Height)

Study Overview
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Brief Summary
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This study is testing if under the tongue olanzapine for schizophrenia, related psychosis, schizoaffective disorder or bipolar disorder will have less weight gain than olanzapine that is swallowed, in patients who are already gaining weight on olanzapine.

Official Title
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BMI Evaluation: Placebo and Active Comparator Trial of Olanzapine Zydis Pills Used Sublingually (PLATYPUS)

Conditions
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Schizophrenia, Schizoaffective Disorder, Bipolar Disorder

Intervention / Treatment
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* Drug: Sublingual orally disintegrating olanzapine (SODO)
* Drug: Oral olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Patients must): Be at least 18 years old Have gained weight while taking olanzapine Be able to visit the doctor's office seven times over 4 months (17 weeks) Exclusion Criteria (Patients must NOT): Have started a weight loss program within the last 8 weeks Have an illness that might affect patient's weight during the study Have an allergy to phenylalanine, mannitol or saccharine Be taking any medication (except for olanzapine) that might affect patient's weight

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Sublingual orally disintegrating olanzapine (SODO) | Drug: Sublingual orally disintegrating olanzapine (SODO)<br>* 5 to 20mg dose, supplied in 5mg tablet strength, tablet should be placed under tongue for at least 60 seconds, daily for 16 weeks.<br>* Other names: Zydis;|
| Active Comparator: B<br>Oral olanzapine | Drug: Oral olanzapine<br>* 5 to 20mg dose, supplied in 5mg tablet strength, oral administration (tablets swallowed), daily for 16 weeks.<br>* Other names: Zyprexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course of Change From Baseline in Body Mass Index (BMI) | Body mass index is an estimate of body fat based on body weight divided by height squared. Comparison of changes at various time points throughout the study. Change = Time point value minus baseline (Visit 2) value. | Visit 2 (Baseline) to Visit 7 (16 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) | Body mass index is an estimate of body fat based on body weight divided by height squared. Comparison of change from baseline to endpoint. Change = Endpoint (Week 16) minus Baseline (Week 0) | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) for the Treatment Completers | Body mass index is an estimate of body fat based on body weight divided by height squared. Comparisons of change from baseline to endpoint between participants who completed their treatment. Change = Endpoint value minus Baseline value. | Visit 2 (Baseline) and Visit 7 (16 Weeks) | 
| Mean Change From Baseline to 16 Week Endpoint in Weight | Weight of undressed patient (undergarments allowed), measured preferably at the same time each day. | Visit 2 (Baseline) and Visit 7 (16 Weeks) | 
| Mean Change From Baseline to 16 Week Endpoint in Waist Circumference | Waist circumference is measured on a bare abodomen just above the hip bone. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Percentage loss of body weight = 100*(postbaseline weight - baseline weight)/baseline weight | Visit 2 (Baseline) to Visit 7 (Week 16) | 
| Number of Participants Discontinuing the Trial by Visit (Week) | The number of participants who discontinued by visit (non-cumulative). | Visit 2 (Baseline) to Visit 7 (Week 16) | 
| Change From Baseline to 16 Week Endpoint in Subjective Appetite Using a Visual Analog Scale | Participant chooses where they think their appetite lies on a 10 centimeter line between two anchors (0 - very poor appetite and 10 - very strong appetite). The possible range of scores is 0 to 100 and represents millimeters on the 10 centimeter line. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Sitting blood pressure, taken from the same arm. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in Fasting Lipoproteins (Total Cholesterol, High-Density Lipoprotein Cholesterol [HDL-Cholesterol], Low-Density Lipoprotein Cholesterol [LDL-Cholesterol] [Calculated], and Triglycerides) | Patients should be fasting a minimum of eight hours prior to lipoprotein measurements. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Change From Baseline to 16 Week Endpoint in Fasting Plasma Glucose | Patients should be fasting a minimum of eight hours prior to plasma glucose measurement. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in Fasting Serum Insulin | Patients should be fasting a minimum of eight hours prior to serum insulin measurement. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in Glycosylated Hemoglobin |  | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Changes From Baseline to 16 Week Endpoint Homeostasis Model Assessments of Insulin Sensitivity HOMA-S (Calculated) | HOMA-S is an estimate of insulin sensitivity. The HOMA model is a computer model of the glucose insulin feedback system in the fasted state. The model consists of a number of non-linear empirical equations describing the functions of organs and tissues involved in glucose regulation. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Number of Participants Meeting a Definition for the Presence of Metabolic Syndrome as Defined by Adult Treatment Panel III (ATP III) Criteria at Baseline and 16 Week Endpoint | Patient meets definition of metabolic syndrome if they have >=3 risk factors: Waist circumference (men>102cm, women>88cm); triglycerides >=1.7mmol/L; HDL cholesterol (men<1.04mmol/L, women<1.30mmol/L); blood pressure >135/>=85 mmHg; Fasting glucose >=6.1mmol/L | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in the Clinical Global Impression-Severity (CGI-S) Scale | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in the Subjective Well-Being Under Neuroleptics (SWN) Scale | Measures subjective well-being for previous 7 days. 20 items covering 5 health domains (subscales) (4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). Subscale scores range from 1 to 24. Total score ranges from 1 to 120. | Visit 2 (Baseline) and Visit 7 (Week 16) | 
| Mean Change From Baseline to 16 Week Endpoint in the Global Assessment of Functioning (GAF) Scale | Measures physician's judgment of a patient's overall level of functioning. Ratings are based on a scale of 1 to 100, with the following classification range: 1-10 (severely impaired) to 91-100 (superior functioning). | Visit 2 (Baseline) and Visit 7 (Week 16) |