Schizoaffective Disorders, Schizophrenia
Conditions
Brief summary
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
Interventions
DRUGolanzapine
5-20 milligrams (mg), oral, daily for 22 weeks.
DRUGamantadine
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.
DRUGmetformin
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.
DRUGzonisamide
Zonisamide, 100-400mg, oral, daily.
BEHAVIORALWellness education
weight management
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to Endpoint in Weight | Baseline to endpoint (22 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Baseline to endpoint (22 weeks) | — |
| Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Baseline to endpoint (22 weeks) | — |
| Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Baseline to endpoint (22 weeks) | — |
| Mean Change From Baseline to Endpoint in Fasting Glucose | Baseline to endpoint (22 weeks) | — |
| Mean Change From Baseline to Endpoint in Fasting Triglycerides | Baseline to endpoint (22 weeks) | — |
| Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Baseline to endpoint (22 weeks) | The BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Each item is rated on a scale from 1 (symptom not present) to 7 (symptom extremely severe). The BPRS total score ranges from 18 to 126. |
| Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to endpoint (22 weeks) | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Baseline to endpoint (22 weeks) | 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). |
| Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | Baseline to endpoint (22 weeks) | To understand the drivers of weight gain as indicated by the correlation between weight changes and changes in the Eating Inventory (EI) and Food Craving Inventory (FCI). The EI is a 51-item inventory that measures dietary restraint, disinhibition, and perceived hunger. The FCI is a 28-item instrument measuring the frequency over the past month of general cravings and cravings for specific types of foods, namely: high fats, sweets, carbohydrates/starches, and fast-food fats. Correlations were computed on the combined treatment groups. |
| Mean Change From Baseline to Endpoint in Hemoglobin A1c | Baseline to endpoint (22 weeks) | — |
Countries
Brazil, Israel, Mexico, Puerto Rico, Russia, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. | 50 |
| Olanzapine + Amantadine Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms). | 76 |
| Olanzapine + Metformin Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms). | 73 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 8 | 4 |
| Overall Study | Clinical Relapse | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 | 2 |
| Overall Study | Physician Decision | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 | 3 |
| Overall Study | Sponsor Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 12 | 9 |
Baseline characteristics
| Characteristic | Olanzapine + Amantadine | Total | Olanzapine + Metformin | Olanzapine |
|---|---|---|---|---|
| Age Continuous | 38.2 years STANDARD_DEVIATION 11.4 | 38.5 years STANDARD_DEVIATION 11.95 | 38.7 years STANDARD_DEVIATION 12.01 | 38.7 years STANDARD_DEVIATION 12.89 |
| Body Mass Index (BMI) | 27.3 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 4.67 | 27.1 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 4.68 | 27.0 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 4.84 | 27.0 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 4.53 |
| Onset Age | 26.44 years STANDARD_DEVIATION 9.98 | 25.15 years STANDARD_DEVIATION 9.32 | 24.40 years STANDARD_DEVIATION 9.18 | 24.35 years STANDARD_DEVIATION 8.42 |
| Previous Number of Episodes | 2.19 number of episodes STANDARD_DEVIATION 5.9 | 2.04 number of episodes STANDARD_DEVIATION 5.06 | 2.22 number of episodes STANDARD_DEVIATION 5.77 | 1.53 number of episodes STANDARD_DEVIATION 1.02 |
| Race/Ethnicity African | 10 participants | 16 participants | 4 participants | 2 participants |
| Race/Ethnicity Caucasian | 30 participants | 87 participants | 34 participants | 23 participants |
| Race/Ethnicity East Asian | 15 participants | 39 participants | 14 participants | 10 participants |
| Race/Ethnicity Hispanic | 20 participants | 52 participants | 18 participants | 14 participants |
| Race/Ethnicity Native American | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity West Asian | 1 participants | 4 participants | 2 participants | 1 participants |
| Region of Enrollment Israel | 8 participants | 22 participants | 9 participants | 5 participants |
| Region of Enrollment Korea, Republic of | 14 participants | 36 participants | 13 participants | 9 participants |
| Region of Enrollment Mexico | 9 participants | 27 participants | 11 participants | 7 participants |
| Region of Enrollment Puerto Rico | 8 participants | 18 participants | 5 participants | 5 participants |
| Region of Enrollment Russian Federation | 15 participants | 40 participants | 14 participants | 11 participants |
| Region of Enrollment United States | 22 participants | 56 participants | 21 participants | 13 participants |
| Sex: Female, Male Female | 30 Participants | 79 Participants | 30 Participants | 19 Participants |
| Sex: Female, Male Male | 46 Participants | 120 Participants | 43 Participants | 31 Participants |
| Type of Diagnosis Schizoaffective | 15 participants | 41 participants | 18 participants | 8 participants |
| Type of Diagnosis Schizophrenia | 61 participants | 158 participants | 55 participants | 42 participants |
| Weight | 79.1 kilograms STANDARD_DEVIATION 17.27 | 77.5 kilograms STANDARD_DEVIATION 16.62 | 76.2 kilograms STANDARD_DEVIATION 16.22 | 77.0 kilograms STANDARD_DEVIATION 16.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / — | 38 / — | 46 / — |
| serious Total, serious adverse events | 5 / — | 4 / — | 4 / — |
Outcome results
Primary
Change From Baseline to Endpoint in Weight
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Weight | 2.76 kilograms | Standard Error 0.75 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Weight | 2.40 kilograms | Standard Error 0.65 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Weight | 0.65 kilograms | Standard Error 0.63 |
Comparison: To detect a difference between treatment arms of 3.06 kg in mean weight change from baseline to endpoint, 150 patients must be enrolled in stepped intervention arm and 50 in control arm. Assuming a standard deviation of 6.87 kg, there is 80% power to detect a difference between treatment arms on a 1-sided 2-sample t-test at the 5% significance level. Primary analysis was the comparison of mean weight change for 'olanzapine only' versus pooled 'olanzapine \& adjunctive treatment' arm at Week 22.p-value: 0.065Mixed Models Analysis
Comparison: Hypothesis=weight gain associated with olanzapine can be prevented or mitigated with an adjunctive pharmacological algorithm.p-value: 0.113Mixed Models Analysis
p-value: 0.036Mixed Models Analysis
Secondary
Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score
The BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Each item is rated on a scale from 1 (symptom not present) to 7 (symptom extremely severe). The BPRS total score ranges from 18 to 126.
Time frame: Baseline to endpoint (22 weeks)
Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Baseline | 48.24 units on a scale | Standard Deviation 15.98 |
| Olanzapine | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Change from Baseline | -13.89 units on a scale | Standard Deviation 18.61 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Baseline | 45.90 units on a scale | Standard Deviation 12.44 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Change from Baseline | -9.90 units on a scale | Standard Deviation 11.24 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Baseline | 47.00 units on a scale | Standard Deviation 14.18 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | Change from Baseline | -9.72 units on a scale | Standard Deviation 14.15 |
p-value: 0.122ANCOVA
p-value: 0.225ANCOVA
p-value: 0.124ANCOVA
Secondary
Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S)
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).
Time frame: Baseline to endpoint (22 weeks)
Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Baseline | 4.06 units on a scale | Standard Deviation 1.24 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Change from Baseline | -0.98 units on a scale | Standard Deviation 1.13 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Baseline | 4.03 units on a scale | Standard Deviation 1.07 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Change from Baseline | -0.72 units on a scale | Standard Deviation 1.14 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Baseline | 4.00 units on a scale | Standard Deviation 1.13 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Change from Baseline | -0.79 units on a scale | Standard Deviation 1.03 |
p-value: 0.474ANCOVA
p-value: 0.404ANCOVA
p-value: 0.652ANCOVA
Secondary
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline to endpoint (22 weeks)
Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 12.76 units on a scale | Standard Deviation 8.08 |
| Olanzapine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Change from Baseline | -6.39 units on a scale | Standard Deviation 8.37 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 14.22 units on a scale | Standard Deviation 11.14 |
| Olanzapine + Amantadine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Change from Baseline | -4.12 units on a scale | Standard Deviation 7.2 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 15.40 units on a scale | Standard Deviation 9.21 |
| Olanzapine + Metformin | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Change from Baseline | -4.36 units on a scale | Standard Deviation 7.47 |
p-value: 0.02ANCOVA
p-value: 0.037ANCOVA
p-value: 0.038ANCOVA
Secondary
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
To understand the drivers of weight gain as indicated by the correlation between weight changes and changes in the Eating Inventory (EI) and Food Craving Inventory (FCI). The EI is a 51-item inventory that measures dietary restraint, disinhibition, and perceived hunger. The FCI is a 28-item instrument measuring the frequency over the past month of general cravings and cravings for specific types of foods, namely: high fats, sweets, carbohydrates/starches, and fast-food fats. Correlations were computed on the combined treatment groups.
Time frame: Baseline to endpoint (22 weeks)
Population: N=Pairs of Observations for the combined treatment groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Disinhibition | -0.034 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Cognitive Restraint | -0.273 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Hunger | -0.150 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Carbohydrates/Starches (N=186, N=141) | 0.013 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Fast Food Fats (N=188, N=140) | -0.019 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: High Fats (N=186, N=138) | 0.051 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Sweets (N=187, N=140) | 0.022 correlation |
| Olanzapine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Total Score (N=184, N=137) | 0.039 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Total Score (N=184, N=137) | -0.000 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Disinhibition | 0.285 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Fast Food Fats (N=188, N=140) | 0.047 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Cognitive Restraint | -0.038 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Sweets (N=187, N=140) | -0.008 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | EI: Hunger | 0.148 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: High Fats (N=186, N=138) | 0.043 correlation |
| Olanzapine + Amantadine | Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | FCI: Carbohydrates/Starches (N=186, N=141) | -0.064 correlation |
Secondary
Mean Change From Baseline to Endpoint in Fasting Glucose
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Glucose | Baseline | 5.32 millimole per Liter (mmol/L) | Standard Deviation 0.46 |
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Glucose | Change from Baseline | 0.26 millimole per Liter (mmol/L) | Standard Deviation 0.99 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Glucose | Baseline | 5.25 millimole per Liter (mmol/L) | Standard Deviation 0.78 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Glucose | Change from Baseline | 0.10 millimole per Liter (mmol/L) | Standard Deviation 0.48 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Glucose | Baseline | 5.28 millimole per Liter (mmol/L) | Standard Deviation 0.63 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Glucose | Change from Baseline | 0.01 millimole per Liter (mmol/L) | Standard Deviation 0.58 |
p-value: 0.339ANCOVA
p-value: 0.499ANCOVA
p-value: 0.833ANCOVA
Secondary
Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
Time frame: Baseline to endpoint (22 weeks)
Population: Number of randomized participants with a baseline and at least one post-baseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Baseline | 1.25 millimole per liter (mmol/L) | Standard Deviation 0.29 |
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Change from Baseline | -0.00 millimole per liter (mmol/L) | Standard Deviation 0.23 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Baseline | 1.26 millimole per liter (mmol/L) | Standard Deviation 0.36 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Change from Baseline | -0.11 millimole per liter (mmol/L) | Standard Deviation 0.25 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Baseline | 1.22 millimole per liter (mmol/L) | Standard Deviation 0.35 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol | Change from Baseline | -0.08 millimole per liter (mmol/L) | Standard Deviation 0.24 |
p-value: 0.017ANCOVA
p-value: 0.015ANCOVA
p-value: 0.071ANCOVA
Secondary
Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Baseline | 3.02 millimole per Liter (mmol/L) | Standard Deviation 0.88 |
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Change from Baseline | 0.16 millimole per Liter (mmol/L) | Standard Deviation 0.6 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Baseline | 3.06 millimole per Liter (mmol/L) | Standard Deviation 1.03 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Change from Baseline | -0.04 millimole per Liter (mmol/L) | Standard Deviation 0.95 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Baseline | 2.91 millimole per Liter (mmol/L) | Standard Deviation 0.93 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol | Change from Baseline | -0.02 millimole per Liter (mmol/L) | Standard Deviation 0.84 |
p-value: 0.152ANCOVA
p-value: 0.35ANCOVA
p-value: 0.123ANCOVA
Secondary
Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Baseline | 5.01 millimole per Liter (mmol/L) | Standard Deviation 1 |
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Change from Baseline | 0.36 millimole per Liter (mmol/L) | Standard Deviation 0.84 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Baseline | 5.03 millimole per Liter (mmol/L) | Standard Deviation 1.09 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Change from Baseline | 0.01 millimole per Liter (mmol/L) | Standard Deviation 1.06 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Baseline | 4.91 millimole per Liter (mmol/L) | Standard Deviation 1.21 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Total Cholesterol | Change from Baseline | -0.08 millimole per Liter (mmol/L) | Standard Deviation 0.92 |
p-value: 0.173ANCOVA
p-value: 0.016ANCOVA
p-value: 0.029ANCOVA
Secondary
Mean Change From Baseline to Endpoint in Fasting Triglycerides
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Baseline | 1.58 millimoles per Liter (mmol/L) | Standard Deviation 0.81 |
| Olanzapine | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Change from Baseline | 0.33 millimoles per Liter (mmol/L) | Standard Deviation 1.01 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Baseline | 1.61 millimoles per Liter (mmol/L) | Standard Deviation 0.76 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Change from Baseline | 0.35 millimoles per Liter (mmol/L) | Standard Deviation 0.88 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Baseline | 1.68 millimoles per Liter (mmol/L) | Standard Deviation 1 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Fasting Triglycerides | Change from Baseline | 0.06 millimoles per Liter (mmol/L) | Standard Deviation 0.64 |
p-value: 0.498ANCOVA
p-value: 0.637ANCOVA
p-value: 0.125ANCOVA
Secondary
Mean Change From Baseline to Endpoint in Hemoglobin A1c
Time frame: Baseline to endpoint (22 weeks)
Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Baseline | 5.51 percent hemoglobin A1c | Standard Deviation 0.46 |
| Olanzapine | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Change from Baseline | 0.09 percent hemoglobin A1c | Standard Deviation 0.45 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Baseline | 5.48 percent hemoglobin A1c | Standard Deviation 0.39 |
| Olanzapine + Amantadine | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Change from Baseline | 0.10 percent hemoglobin A1c | Standard Deviation 0.37 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Baseline | 5.53 percent hemoglobin A1c | Standard Deviation 0.37 |
| Olanzapine + Metformin | Mean Change From Baseline to Endpoint in Hemoglobin A1c | Change from Baseline | -0.03 percent hemoglobin A1c | Standard Deviation 0.25 |
p-value: 0.278ANCOVA
p-value: 0.976ANCOVA
p-value: 0.049ANCOVA