Bipolar Disorder, Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
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.
Interventions
DRUGSublingual orally disintegrating olanzapine (SODO)
5 to 20mg dose, supplied in 5mg tablet strength, tablet should be placed under tongue for at least 60 seconds, daily for 16 weeks.
DRUGOral olanzapine
5 to 20mg dose, supplied in 5mg tablet strength, oral administration (tablets swallowed), daily for 16 weeks.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Course of Change From Baseline in Body Mass Index (BMI) | Visit 2 (Baseline) to Visit 7 (16 Weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) for the Treatment Completers | Visit 2 (Baseline) and Visit 7 (16 Weeks) | 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. |
| Mean Change From Baseline to 16 Week Endpoint in Weight | Visit 2 (Baseline) and Visit 7 (16 Weeks) | Weight of undressed patient (undergarments allowed), measured preferably at the same time each day. |
| Mean Change From Baseline to 16 Week Endpoint in Waist Circumference | Visit 2 (Baseline) and Visit 7 (Week 16) | Waist circumference is measured on a bare abodomen just above the hip bone. |
| Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Visit 2 (Baseline) to Visit 7 (Week 16) | Percentage loss of body weight = 100\*(postbaseline weight - baseline weight)/baseline weight |
| Number of Participants Discontinuing the Trial by Visit (Week) | Visit 2 (Baseline) to Visit 7 (Week 16) | The number of participants who discontinued by visit (non-cumulative). |
| Change From Baseline to 16 Week Endpoint in Subjective Appetite Using a Visual Analog Scale | Visit 2 (Baseline) and Visit 7 (Week 16) | 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. |
| Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Visit 2 (Baseline) and Visit 7 (Week 16) | Sitting blood pressure, taken from the same arm. |
| 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) | Visit 2 (Baseline) and Visit 7 (Week 16) | Patients should be fasting a minimum of eight hours prior to lipoprotein measurements. |
| Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) | Visit 2 (Baseline) and Visit 7 (Week 16) | 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) |
| Mean Change From Baseline to 16 Week Endpoint in Fasting Serum Insulin | Visit 2 (Baseline) and Visit 7 (Week 16) | Patients should be fasting a minimum of eight hours prior to serum insulin measurement. |
| 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) | Visit 2 (Baseline) and Visit 7 (Week 16) | 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. |
| 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 | Visit 2 (Baseline) and Visit 7 (Week 16) | 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 |
| Mean Change From Baseline to 16 Week Endpoint in the Clinical Global Impression-Severity (CGI-S) Scale | Visit 2 (Baseline) and Visit 7 (Week 16) | 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). |
| Mean Change From Baseline to 16 Week Endpoint in the Subjective Well-Being Under Neuroleptics (SWN) Scale | Visit 2 (Baseline) and Visit 7 (Week 16) | 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. |
| Mean Change From Baseline to 16 Week Endpoint in the Global Assessment of Functioning (GAF) Scale | Visit 2 (Baseline) and Visit 7 (Week 16) | 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). |
| Change From Baseline to 16 Week Endpoint in Fasting Plasma Glucose | Visit 2 (Baseline) and Visit 7 (Week 16) | Patients should be fasting a minimum of eight hours prior to plasma glucose measurement. |
Countries
Canada, Mexico, Netherlands, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SODO Sublingual orally disintegrating olanzapine (SODO); 5 to 20 mg dose, supplied in 5 mg tablet strength, tablet should be placed under tongue for at least 60 seconds, daily for 16 weeks | 84 |
| SOT Standard oral olanzapine tablet; 5 to 20 mg dose, supplied in 5 mg tablet strength, oral administration (tablets swallowed), daily for 16 weeks | 65 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | Noncompliance | 2 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Protocol entry criteria not met | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | SOT | SODO | Total |
|---|---|---|---|
| Age Continuous | 38.7 years STANDARD_DEVIATION 12.23 | 38.6 years STANDARD_DEVIATION 13.13 | 38.6 years STANDARD_DEVIATION 12.7 |
| Blood Pressure Diastolic Blood Pressure | 75.8 mm Hg STANDARD_DEVIATION 9.15 | 77.6 mm Hg STANDARD_DEVIATION 9.62 | 76.8 mm Hg STANDARD_DEVIATION 9.43 |
| Blood Pressure Systolic Blood Pressure | 119.0 mm Hg STANDARD_DEVIATION 12.49 | 120.3 mm Hg STANDARD_DEVIATION 16.45 | 119.7 mm Hg STANDARD_DEVIATION 14.82 |
| Body Mass Index | 28.3 kilograms/meters-squared STANDARD_DEVIATION 4.76 | 28.0 kilograms/meters-squared STANDARD_DEVIATION 5.63 | 28.1 kilograms/meters-squared STANDARD_DEVIATION 5.26 |
| Clinical Global Impression-Severity Scale | 3.2 units on a scale STANDARD_DEVIATION 0.85 | 3.0 units on a scale STANDARD_DEVIATION 0.78 | 3.1 units on a scale STANDARD_DEVIATION 0.81 |
| Fasting Glucose | 5.0 millimole/Liter STANDARD_DEVIATION 0.46 | 5.1 millimole/Liter STANDARD_DEVIATION 0.77 | 5.1 millimole/Liter STANDARD_DEVIATION 0.65 |
| Fasting Insulin | 10.0 micro International Unit/milliliter STANDARD_DEVIATION 7.18 | 13.5 micro International Unit/milliliter STANDARD_DEVIATION 14.65 | 11.9 micro International Unit/milliliter STANDARD_DEVIATION 12.06 |
| Fasting Lipoproteins High-Density Lipoprotein Cholesterol | 1.3 millimole/Liter STANDARD_DEVIATION 0.34 | 1.2 millimole/Liter STANDARD_DEVIATION 0.4 | 1.3 millimole/Liter STANDARD_DEVIATION 0.37 |
| Fasting Lipoproteins Low-Density Lipoprotein Cholesterol | 3.0 millimole/Liter STANDARD_DEVIATION 0.88 | 3.1 millimole/Liter STANDARD_DEVIATION 0.81 | 3.1 millimole/Liter STANDARD_DEVIATION 0.84 |
| Fasting Lipoproteins Total Cholesterol | 5.1 millimole/Liter STANDARD_DEVIATION 1.01 | 5.1 millimole/Liter STANDARD_DEVIATION 1.01 | 5.1 millimole/Liter STANDARD_DEVIATION 1 |
| Fasting Lipoproteins Triglycerides | 1.7 millimole/Liter STANDARD_DEVIATION 0.9 | 1.7 millimole/Liter STANDARD_DEVIATION 0.77 | 1.7 millimole/Liter STANDARD_DEVIATION 0.83 |
| Global Assessment of Functioning Scale | 62.5 units on a scale STANDARD_DEVIATION 12.39 | 63.4 units on a scale STANDARD_DEVIATION 12.82 | 63.0 units on a scale STANDARD_DEVIATION 12.6 |
| Glycosylated Hemoglobin | 5.5 percent STANDARD_DEVIATION 0.38 | 5.5 percent STANDARD_DEVIATION 0.45 | 5.5 percent STANDARD_DEVIATION 0.42 |
| Height | 168.9 centimeters STANDARD_DEVIATION 10.23 | 170.0 centimeters STANDARD_DEVIATION 10.18 | 169.5 centimeters STANDARD_DEVIATION 10.18 |
| Presence of Metabolic Syndrome No | 49 participants | 64 participants | 113 participants |
| Presence of Metabolic Syndrome Unknown | 0 participants | 2 participants | 2 participants |
| Presence of Metabolic Syndrome Yes | 16 participants | 18 participants | 34 participants |
| Psychiatric Illness Bipolar disorder | 14 participants | 27 participants | 41 participants |
| Psychiatric Illness Other related psychiatric disorder | 1 participants | 1 participants | 2 participants |
| Psychiatric Illness Schizoaffective disorder | 12 participants | 3 participants | 15 participants |
| Psychiatric Illness Schizophrenia | 36 participants | 46 participants | 82 participants |
| Psychiatric Illness Schizophreniform | 2 participants | 7 participants | 9 participants |
| Race/Ethnicity African Descent | 4 participants | 11 participants | 15 participants |
| Race/Ethnicity Caucasian | 36 participants | 42 participants | 78 participants |
| Race/Ethnicity East/Southeast Asian | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity First Nations | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity Hispanic | 23 participants | 27 participants | 50 participants |
| Race/Ethnicity Other | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 21 participants | 29 participants | 50 participants |
| Region of Enrollment Mexico | 23 participants | 27 participants | 50 participants |
| Region of Enrollment Netherlands | 3 participants | 5 participants | 8 participants |
| Region of Enrollment United States | 18 participants | 23 participants | 41 participants |
| Sex: Female, Male Female | 32 Participants | 36 Participants | 68 Participants |
| Sex: Female, Male Male | 33 Participants | 48 Participants | 81 Participants |
| Subjective Appetite (Visual Analog Scale) | 65.7 units on a scale STANDARD_DEVIATION 19.24 | 62.5 units on a scale STANDARD_DEVIATION 20.85 | 63.9 units on a scale STANDARD_DEVIATION 20.16 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Emotional Regulation Subscale | 17.4 units on a scale STANDARD_DEVIATION 3.82 | 17.6 units on a scale STANDARD_DEVIATION 4.07 | 17.5 units on a scale STANDARD_DEVIATION 3.95 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Mental Functioning Subscale | 16.7 units on a scale STANDARD_DEVIATION 4.2 | 16.7 units on a scale STANDARD_DEVIATION 4.02 | 16.7 units on a scale STANDARD_DEVIATION 4.09 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Physical Functioning Subscale | 17.2 units on a scale STANDARD_DEVIATION 3.26 | 17.0 units on a scale STANDARD_DEVIATION 3.53 | 17.1 units on a scale STANDARD_DEVIATION 3.41 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Self-Control Subscale | 17.3 units on a scale STANDARD_DEVIATION 4.15 | 17.0 units on a scale STANDARD_DEVIATION 3.45 | 17.1 units on a scale STANDARD_DEVIATION 3.76 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Social Integration Subscale | 17.0 units on a scale STANDARD_DEVIATION 3.97 | 17.0 units on a scale STANDARD_DEVIATION 4.38 | 17.0 units on a scale STANDARD_DEVIATION 4.19 |
| Subjective Well-Being Under Neuroleptic Treatment - Short Form Total Score | 85.6 units on a scale STANDARD_DEVIATION 15 | 85.5 units on a scale STANDARD_DEVIATION 15.59 | 85.5 units on a scale STANDARD_DEVIATION 15.28 |
| Waist Circumference | 97.2 centimeters STANDARD_DEVIATION 12.97 | 96.1 centimeters STANDARD_DEVIATION 13.24 | 96.6 centimeters STANDARD_DEVIATION 13.09 |
| Weight | 81.2 kilograms STANDARD_DEVIATION 17.05 | 81.1 kilograms STANDARD_DEVIATION 18.97 | 81.1 kilograms STANDARD_DEVIATION 18.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / — | 32 / — |
| serious Total, serious adverse events | 2 / — | 0 / — |
Outcome results
Primary
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.
Time frame: Visit 2 (Baseline) to Visit 7 (16 Weeks)
Population: Intention to treat
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SODO | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 4 (N=79, N=63) | 0.25 kilograms/square meters | Standard Error 0.08 |
| SODO | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 12 (N=70, N=54) | 0.47 kilograms/square meters | Standard Error 0.16 |
| SODO | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 8 (N=75, N=58) | 0.34 kilograms/square meters | Standard Error 0.12 |
| SODO | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 16 (N=67, N=51) | 0.52 kilograms/square meters | Standard Error 0.18 |
| SODO | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 2 (N=82, N=63) | 0.09 kilograms/square meters | Standard Error 0.06 |
| SOT | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 16 (N=67, N=51) | 0.72 kilograms/square meters | Standard Error 0.2 |
| SOT | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 2 (N=82, N=63) | 0.16 kilograms/square meters | Standard Error 0.07 |
| SOT | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 4 (N=79, N=63) | 0.27 kilograms/square meters | Standard Error 0.09 |
| SOT | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 8 (N=75, N=58) | 0.32 kilograms/square meters | Standard Error 0.13 |
| SOT | Time Course of Change From Baseline in Body Mass Index (BMI) | Week 12 (N=70, N=54) | 0.54 kilograms/square meters | Standard Error 0.18 |
p-value: 0.428Mixed Models Analysis
p-value: 0.859Mixed Models Analysis
p-value: 0.885Mixed Models Analysis
p-value: 0.784Mixed Models Analysis
p-value: 0.465Mixed Models Analysis
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Change From Baseline to 16 Week Endpoint in Fasting Plasma Glucose | 0.2 millimole/Liter | Standard Deviation 0.79 |
| SOT | Change From Baseline to 16 Week Endpoint in Fasting Plasma Glucose | 0.1 millimole/Liter | Standard Deviation 0.48 |
p-value: 0.227Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SODO | Change From Baseline to 16 Week Endpoint in Subjective Appetite Using a Visual Analog Scale | -8.21 units on a scale | Standard Error 2.26 |
| SOT | Change From Baseline to 16 Week Endpoint in Subjective Appetite Using a Visual Analog Scale | -5.02 units on a scale | Standard Error 2.59 |
p-value: 0.344Mixed Models Analysis
Secondary
Mean Change From Baseline to 16 Week Endpoint in Blood Pressure
Sitting blood pressure, taken from the same arm.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Systolic Blood Pressure | 0.1 mm Hg | Standard Deviation 11.62 |
| SODO | Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Diastolic Blood Pressure | 0.3 mm Hg | Standard Deviation 7.55 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Systolic Blood Pressure | -0.1 mm Hg | Standard Deviation 10.83 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Blood Pressure | Diastolic Blood Pressure | 0.8 mm Hg | Standard Deviation 8.35 |
p-value: 0.708Rank-Sum Test
p-value: 0.453Rank-Sum Test
Secondary
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)
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) | 0.52 kilograms/square meters | Standard Deviation 1.49 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) | 0.67 kilograms/square meters | Standard Deviation 1.44 |
p-value: 0.44295% CI: [-0.67, 0.3]ANCOVA
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (16 Weeks)
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) for the Treatment Completers | 0.56 kilograms/square meters | Standard Deviation 1.59 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Body Mass Index (BMI) for the Treatment Completers | 0.79 kilograms/square meters | Standard Deviation 1.58 |
p-value: 0.32895% CI: [-0.95, 0.32]ANCOVA
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SODO | 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) | Total Cholesterol | 0.1 millimole/Liter | Standard Deviation 0.74 |
| SODO | 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) | High-Density Lipoprotein Cholesterol | -0.0 millimole/Liter | Standard Deviation 0.24 |
| SODO | 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) | Low-Density Lipoprotein Cholesterol (N=73, N=57) | 0.1 millimole/Liter | Standard Deviation 0.66 |
| SODO | 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) | Triglycerides | 0.1 millimole/Liter | Standard Deviation 0.84 |
| SOT | 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) | Triglycerides | 0.0 millimole/Liter | Standard Deviation 1.01 |
| SOT | 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) | Total Cholesterol | 0.2 millimole/Liter | Standard Deviation 0.79 |
| SOT | 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) | Low-Density Lipoprotein Cholesterol (N=73, N=57) | 0.2 millimole/Liter | Standard Deviation 0.53 |
| SOT | 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) | High-Density Lipoprotein Cholesterol | -0.0 millimole/Liter | Standard Deviation 0.24 |
p-value: 0.187Cochran-Mantel-Haenszel
p-value: 0.163Cochran-Mantel-Haenszel
p-value: 0.323Cochran-Mantel-Haenszel
p-value: 0.581Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Fasting Serum Insulin | 2.4 microIU/milliliter | Standard Deviation 17.72 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Fasting Serum Insulin | -0.1 microIU/milliliter | Standard Deviation 5.52 |
p-value: 0.02Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline to 16 Week Endpoint in Glycosylated Hemoglobin
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Glycosylated Hemoglobin | 0.0 percent | Standard Deviation 0.24 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Glycosylated Hemoglobin | 0.0 percent | Standard Deviation 0.28 |
p-value: 0.834Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in the Clinical Global Impression-Severity (CGI-S) Scale | -0.26 units on a scale | Standard Error 0.07 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in the Clinical Global Impression-Severity (CGI-S) Scale | -0.09 units on a scale | Standard Error 0.08 |
p-value: 0.118Mixed Models Analysis
Secondary
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).
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in the Global Assessment of Functioning (GAF) Scale | 4.61 units on a scale | Standard Error 1.05 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in the Global Assessment of Functioning (GAF) Scale | 2.72 units on a scale | Standard Error 1.2 |
p-value: 0.229Mixed Models Analysis
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in the Subjective Well-Being Under Neuroleptics (SWN) Scale | 4.79 units on a scale | Standard Error 1.52 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in the Subjective Well-Being Under Neuroleptics (SWN) Scale | 1.60 units on a scale | Standard Error 1.73 |
p-value: 0.161Mixed Models Analysis
Secondary
Mean Change From Baseline to 16 Week Endpoint in Waist Circumference
Waist circumference is measured on a bare abodomen just above the hip bone.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Waist Circumference | 1.13 centimeters | Standard Deviation 5.25 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Waist Circumference | 0.77 centimeters | Standard Deviation 5.3 |
p-value: 0.91495% CI: [-1.65, 1.84]ANCOVA
Secondary
Mean Change From Baseline to 16 Week Endpoint in Weight
Weight of undressed patient (undergarments allowed), measured preferably at the same time each day.
Time frame: Visit 2 (Baseline) and Visit 7 (16 Weeks)
Population: Intention to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Change From Baseline to 16 Week Endpoint in Weight | 1.42 kilograms | Standard Error 0.5 |
| SOT | Mean Change From Baseline to 16 Week Endpoint in Weight | 2.08 kilograms | Standard Error 0.57 |
p-value: 0.385Mixed Models Analysis
Secondary
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.
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Safety population with last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SODO | Mean Changes From Baseline to 16 Week Endpoint Homeostasis Model Assessments of Insulin Sensitivity HOMA-S (Calculated) | -18.5 percent sensitivity | Standard Deviation 58.91 |
| SOT | Mean Changes From Baseline to 16 Week Endpoint Homeostasis Model Assessments of Insulin Sensitivity HOMA-S (Calculated) | -9.8 percent sensitivity | Standard Deviation 62.61 |
p-value: 0.022Cochran-Mantel-Haenszel
Secondary
Number of Participants Discontinuing the Trial by Visit (Week)
The number of participants who discontinued by visit (non-cumulative).
Time frame: Visit 2 (Baseline) to Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SODO | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 4 (Week 4) Discontinuations | 3 participants |
| SODO | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 6 (Week 12) Discontinuations | 5 participants |
| SODO | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 5 (Week 8) Discontinuations | 5 participants |
| SODO | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 7 (Week 16) Discontinuations | 3 participants |
| SODO | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 3 (Week 2) Discontinuations | 3 participants |
| SOT | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 7 (Week 16) Discontinuations | 1 participants |
| SOT | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 3 (Week 2) Discontinuations | 1 participants |
| SOT | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 4 (Week 4) Discontinuations | 1 participants |
| SOT | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 5 (Week 8) Discontinuations | 6 participants |
| SOT | Number of Participants Discontinuing the Trial by Visit (Week) | Visit 6 (Week 12) Discontinuations | 6 participants |
Secondary
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
Time frame: Visit 2 (Baseline) and Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SODO | 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 | Baseline - Metabolic Syndrome (N=82, N=65) | 18 participants |
| SODO | 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 | Endpoint - Metabolic Syndrome (N=70, N=52) | 18 participants |
| SOT | 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 | Baseline - Metabolic Syndrome (N=82, N=65) | 16 participants |
| SOT | 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 | Endpoint - Metabolic Syndrome (N=70, N=52) | 10 participants |
p-value: 0.515Fisher Exact
Secondary
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
Time frame: Visit 2 (Baseline) to Visit 7 (Week 16)
Population: Intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SODO | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 4 (N=79, N=63) | 0 participants |
| SODO | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 12 (N=70, N=54) | 3 participants |
| SODO | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 8 (N=75, N=58) | 2 participants |
| SODO | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 16 (N=67, N=51) | 4 participants |
| SODO | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 2 (N=82, N=63) | 0 participants |
| SOT | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 16 (N=67, N=51) | 6 participants |
| SOT | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 2 (N=82, N=63) | 0 participants |
| SOT | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 4 (N=79, N=63) | 1 participants |
| SOT | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 8 (N=75, N=58) | 2 participants |
| SOT | Number of Patients Achieving at Least 5% Loss of Body Weight in Any Post-Baseline Period | Up to Week 12 (N=70, N=54) | 4 participants |
p-value: 0.325Fisher Exact