Schizophrenia
Conditions
Keywords
Paliperidone ER, Olanzapine, Schizophrenia
Brief summary
The purpose of this 6 month study is to compare the metabolic effects of paliperidone ER and olanzapine in patients with schizophrenia, using the ratio of the concentration of lipids (triglycerides (TG)) in the blood to the concentration of good cholesterol (high density lipoproteins (HDL)) in the blood as the primary parameter. Approximately 456 adult patients will participate in this study.
Detailed description
This is a prospective randomized (study medication is assigned by change) open-label, parallel-group, multicenter, 6 month study to compare the metabolic effects of paliperidone ER and olanzapine in patients with schizophrenia using the ratio of the concentration of lipids (triglycerides) in the blood to the concentration of good cholesterol (high density lipoproteins (HDL)) as the primary parameter. Secondary objectives include evaluation of additional parameters related to the total of the actions of the body to keep it alive (metabolic endpoints) and demonstration of non-inferiority of paliperidone ER versus olanzapine in efficacy as measured by Positive and Negative Syndrome Scale (PANSS). Patients previously treated with any oral antipsychotic, except those treated with paliperidone ER, olanzapine or clozapine during the last 6 months, can be enrolled and will be treated with paliperidone ER (6 to 9 mg/day) or olanzapine (10 to 15 mg/day). Patients will be divided into groups according to the metabolic effects of their previous antipsychotic medication (medication that does not increase body weight vs. medication that increases body weight). Throughout the study flexible dosing is allowed based on the investigator discretion. A study treatment period of 6 months is planned for all patients. Medication to treat symptoms like confusion, blurred vision, constipation, dry mouth, light-headedness, difficulty starting and continuing to urinate, and loss of bladder control may continue up to four weeks and should then be tapered off at the discretion of the investigator. Approximately 456 adult patients (228 in each treatment group) will participate in this study. Efficacy will be assessed with the following measures: PANSS (total score and subscale scores), Clinical Global Impression - Severity (CGI-S), Self-rated health status Survey SF-36, and Sleep and daytime drowsiness evaluation scale. The parameters related to the total of the actions of the body to keep it alive (metabolic endpoints) will be assessed with the following: ratio of blood lipids to blood good cholesterol concentrations (TG:HDL ratio) (for this primary evaluation, plasma fasting lipids and good cholesterol concentrations will be measured), fasting plasma insulin and fasting plasma glucose, plasma glucose and insulin concentrations before and after a 75 gram oral glucose tolerance test (OGTT) to asses insulin sensitivity and changes in insulin secretion, fasting good cholesterol, lipids, and glucose levels for the determination of new onset or presence of metabolic syndrome during treatment according to criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII criteria), weight, Body-Mass-Index and waist circumference for the determination of new onset or presence of a medical condition associated with abdominal obesity, abnormalities in glucose, lipid and cholesterol metabolism, and elevated blood pressure that increases the risk of cardiovascular disease and type 2 diabetes (metabolic syndrome) during treatment according to NCEP/ATP III criteria. All patients who receive trial medication (paliperidone ER or olanzapine) at least once will be included in the analysis of the demographic and baseline characteristic data. 2 dosage levels of paliperidone ER (6 or 9mg per day) and 2 of olanzapine (10 and 15mg per day) are available to the patients. Throughout the study flexible dosing is allowed based on the investigator's discretion. Study medication is to be taken in the morning orally, with water. A study treatment period of 6 months is planned for all patients.
Interventions
DRUGolanzapine
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
DRUGpaliperidone ER
6-mg or 9-mg tablet once daily flexible dosing for 6 months
Sponsors
Janssen-Cilag International NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient meets the DSM-IV criteria for schizophrenia * Patient has a PANSS total score at screening of 60 to 100, inclusive * Patient must, in the opinion of the investigator, benefit from treatment with paliperidone ER or olanzapine * Patients on lipid-lowering therapy must be on a stable dose for at least 4 weeks for statins, niacin, ezetimibe and resins or for at least 12 weeks for fibrates * Female patients must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (e.g. prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study * Women of child-bearing potential must have a negative urine pregnancy test at screening * Patient is healthy on the basis of a physical examination and vital signs at screening
Exclusion criteria
* Patient has previously been treated with paliperidone ER, olanzapine, or clozapine within the past 6 months or has never been treated with an antipsychotic before * Treatment with a depot antipsychotic within the past 3 months * Treatment with a mood stabilizer or a recently initiated antidepressant (\<= 3 months) * Patient has abnormal fasting plasma glucose (\> 126 mg/dL) or fasting triglycerides (TG) levels (\> 400 mg/dL) at screening * Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, including recent or present clinically relevant laboratory abnormalities (as deemed by the investigator) * History or current symptoms of tardive dyskinesia * History of neuroleptic malignant syndrome * Pregnant or breast-feeding female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio) | Baseline to End Point (up to 6 months) | Plasma fasting TG and HDL concentrations were measured to determine the TG:HDL ratio. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End Point in High Density Lipoprotein | Baseline to End Point (up to 6 months) | The HDL level was assessed under fasted conditions. |
| Change From Baseline to End Point in Total Cholesterol | Baseline to End Point (up to 6 months) | The total cholesterol level was assessed under fasted conditions. |
| Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT) | Baseline to End Point (up to 6 months) | The level of low density lipoprotein cholesterol was calculated using the Friedwald QT formula. |
| Change From Baseline to End Point in Converted Insulin | Baseline to End Point (up to 6 months) | The insulin level was assessed under fasted conditions. |
| Change From Baseline to End Point in Fasting Glucose | Baseline to End Point (up to 6 months) | — |
| Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B) | Baseline to End Point (up to 6 months) | HOMA-%B is used to assess beta-cell function. HOMA-%B is a dimensionless measure of beta-cell function (higher values present increased insulin secretion for a given glucose level). HOMA-%B is normalized so that lean, healthy individuals will have values of HOMA-%B close to 100%. |
| Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR) | Baseline to End Point (up to 6 months) | HOMA-IR is used to assess insulin resistance (IR). HOMA-IR is a dimensionless measure of insulin resistance (higher values present more insulin resistance. HOMA-IR are normalized so that lean, healthy individuals will have values of HOMA-IR close to 1. |
| Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up | 6 months | Fasting plasma glucose ≥126 mg/dL or 2-hour post-load plasma glucose ≥200 mg/dL during an oral glucose tolerance test (OGTT) or initiated use of glucose-lowering agents during the course of the study. |
| Change From Baseline to End Point in Triglycerides | Baseline to End Point (up to 6 months) | The TG level was assessed under fasted conditions. |
| Number of Patients With Impaired Fasting Glucose | Baseline to End Point (up to 6 months) | Post-baseline glucose level under fasted conditions ≥100 mg/dL but \<126 mg/dL. |
| Change From Baseline at End Point of the Insulinogenic Index | Baseline to End Point (up to 6 months) | The insulinogenic index, defined as (insulin at 30 min - insulin at 0)/(glucose at 30 min \[G(30)\] - glucose at 0 \[G(0)\]) was used as a measure of early insulin secretion in response to the OGTT. Because the index is undefined when G(30)-G(0)=0, and poorly defined when G(30)-G(0)\<0, the index was only calculated when G(30)\>G(0). |
| Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin | Baseline to End Point (up to 6 months) | As another measure of beta-cell function, the relationship between plasma insulin and glucose concentrations during the OGTT was calculated using a simplified version of the method described by Mari et al. (Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90:4888-4894.). |
| Change From Baseline at End Point in Body Weight | Baseline to End Point (up to 6 months) | Patients were weighed lightly clothed. The same amount of clothing had to be worn each time. |
| Change From Baseline at End Point in Body Mass Index (BMI) | Baseline to End Point (up to 6 months) | BMI is calculated by dividing the body weight (in kg) by the square of height (in meters). |
| Change From Baseline at End Point in Waist Circumference | Baseline to End Point (up to 6 months) | Patients had to be instructed to stand erect with abdomen relaxed, arms at sides, feet together, and weight divided equally over both legs. The tape measure was placed around the bare abdomen midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. A nonstretchable tape was evenly placed around the natural waist covering the left and right natural-waist marks. The measurement scale had to face outward, and there could not be any twists in the tape. The tape had to be just touching the skin but not compressing the soft tissue. |
| Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up | 6 months | Metabolic syndrome is defined according the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) of which 3 out of 5 criteria must be met: * waist circumference men \> 102 cm; waist circumference women \> 88 cm * TG ≥ 150 mg/dL * HDL cholesterol men \<40 mg/dL; HDL cholesterol women \<50 mg/dL * Blood pressure systolic ≥ 130 mmHg; Blood pressure diastolic ≥ 85 mmHg * Fasting glucose ≥ 110 mg /dL |
| Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS) | Baseline to End Point (up to 6 months) | PANSS is an investigator-rated 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provided a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme). |
| Number of Patients With Onset of Impaired Glucose Tolerance | Baseline to End Point (up to 6 months) | Glucose ≥140 mg/dL, \<200 mg/dL after a 75g OGTT. |
Countries
Argentina, Egypt, Estonia, France, Greece, Jordan, Latvia, Lebanon, Lithuania, Romania, Slovakia, South Africa, Spain, Turkey (Türkiye)
Participant flow
Pre-assignment details
Three subjects of the 462 enrolled did not receive study medication and were excluded from analysis: 2 subjects were randomized by mistake by the investigator and 1 subject withdrew consent before first intake of study medication. The ITT population consisted of 459 subjects who took at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone ER 6-mg or 9-mg tablet once daily flexible dosing for 6 months | 239 |
| Olanzapine 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months | 220 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 5 |
| Overall Study | Lack of Efficacy | 15 | 6 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Other | 9 | 5 |
| Overall Study | Withdrawal by Subject | 30 | 22 |
Baseline characteristics
| Characteristic | Paliperidone ER | Olanzapine | Total |
|---|---|---|---|
| Age, Continuous | 38.8 years STANDARD_DEVIATION 11.1 | 37.5 years STANDARD_DEVIATION 11.4 | 38.2 years STANDARD_DEVIATION 11.2 |
| Body Mass Index (BMI) | 26.9 kg/m² STANDARD_DEVIATION 6.31 | 27.0 kg/m² STANDARD_DEVIATION 5.73 | 26.9 kg/m² STANDARD_DEVIATION 6.03 |
| Sex: Female, Male Female | 106 Participants | 87 Participants | 193 Participants |
| Sex: Female, Male Male | 133 Participants | 133 Participants | 266 Participants |
| Waist | 92.2 cm STANDARD_DEVIATION 14.4 | 93.3 cm STANDARD_DEVIATION 15.6 | 92.7 cm STANDARD_DEVIATION 14.9 |
| Weight | 75.9 kg STANDARD_DEVIATION 17 | 77.9 kg STANDARD_DEVIATION 16.5 | 76.9 kg STANDARD_DEVIATION 16.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 239 | 93 / 220 |
| serious Total, serious adverse events | 21 / 239 | 12 / 220 |
Outcome results
Primary
Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)
Plasma fasting TG and HDL concentrations were measured to determine the TG:HDL ratio.
Time frame: Baseline to End Point (up to 6 months)
Population: The primary end point analysis set consisted of 413 patients, i.e., all patients who received study medication at least once and had baseline and post-baseline TG and HDL data. Data of patients with missing TG or HDL values or who started or changed lipid-lowering medication during the trial were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio) | -0.08 Ratio | Standard Deviation 1.1 |
| Olanzapine | Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio) | 0.42 Ratio | Standard Deviation 1.19 |
Comparison: Based on available data it was estimated that in the paliperidone ER group the TG:HDL ratio would decrease with 0.15 and that the TG:HDL ratio would increase with 0.25 in the olanzapine group. The common SD of the change was estimated to be 1.4. A sample size of 205 patients in each treatment arm had 80% power to detect a difference of 0.4 in change of TG:HDL ratio after 6 months of treatment in favor of paliperidone ER treatment (Wilcoxon two-sample test with 0.05 two-sided significance level).p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Within-group comparison of the change from baseline at end point.p-value: 0.4718Wilcoxon signed rank test
Comparison: Within-group change from baseline at end point.p-value: <0.0001Wilcoxon signed rank test
Secondary
Change From Baseline at End Point in Body Mass Index (BMI)
BMI is calculated by dividing the body weight (in kg) by the square of height (in meters).
Time frame: Baseline to End Point (up to 6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline at End Point in Body Mass Index (BMI) | 0.43 kg/m² | Standard Deviation 1.59 |
| Olanzapine | Change From Baseline at End Point in Body Mass Index (BMI) | 1.32 kg/m² | Standard Deviation 1.99 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline at End Point in Body Weight
Patients were weighed lightly clothed. The same amount of clothing had to be worn each time.
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline at End Point in Body Weight | 1.16 kg | Standard Deviation 4.57 |
| Olanzapine | Change From Baseline at End Point in Body Weight | 3.81 kg | Standard Deviation 5.87 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Within-group change from baseline to end point.p-value: 0.0001Wilcoxon signed rank test
Comparison: Within-group change from baseline to end point.p-value: <0.0001Wilcoxon signed rank test
Secondary
Change From Baseline at End Point in Waist Circumference
Patients had to be instructed to stand erect with abdomen relaxed, arms at sides, feet together, and weight divided equally over both legs. The tape measure was placed around the bare abdomen midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. A nonstretchable tape was evenly placed around the natural waist covering the left and right natural-waist marks. The measurement scale had to face outward, and there could not be any twists in the tape. The tape had to be just touching the skin but not compressing the soft tissue.
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline at End Point in Waist Circumference | 0.70 cm | Standard Deviation 5.39 |
| Olanzapine | Change From Baseline at End Point in Waist Circumference | 3.38 cm | Standard Deviation 6.18 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin
As another measure of beta-cell function, the relationship between plasma insulin and glucose concentrations during the OGTT was calculated using a simplified version of the method described by Mari et al. (Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90:4888-4894.).
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin | 8.63 pM/mM | Standard Deviation 79.53 |
| Olanzapine | Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin | 17.28 pM/mM | Standard Deviation 94.51 |
p-value: 0.3358Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline at End Point of the Insulinogenic Index
The insulinogenic index, defined as (insulin at 30 min - insulin at 0)/(glucose at 30 min \[G(30)\] - glucose at 0 \[G(0)\]) was used as a measure of early insulin secretion in response to the OGTT. Because the index is undefined when G(30)-G(0)=0, and poorly defined when G(30)-G(0)\<0, the index was only calculated when G(30)\>G(0).
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline at End Point of the Insulinogenic Index | 2.21 pM/mM | Standard Deviation 173.46 |
| Olanzapine | Change From Baseline at End Point of the Insulinogenic Index | 33.78 pM/mM | Standard Deviation 259.56 |
p-value: 0.1308Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Converted Insulin
The insulin level was assessed under fasted conditions.
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Converted Insulin | 2.7397 pmol/L | Standard Deviation 89.9776 |
| Olanzapine | Change From Baseline to End Point in Converted Insulin | 17.2327 pmol/L | Standard Deviation 84.6255 |
p-value: 0.0272Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Fasting Glucose
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Fasting Glucose | -0.2071 mmol/L | Standard Deviation 0.4953 |
| Olanzapine | Change From Baseline to End Point in Fasting Glucose | 0.0769 mmol/L | Standard Deviation 0.4781 |
p-value: 0.1892Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in High Density Lipoprotein
The HDL level was assessed under fasted conditions.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in High Density Lipoprotein | 0.01 mmol/L | Standard Deviation 0.25 |
| Olanzapine | Change From Baseline to End Point in High Density Lipoprotein | -0.04 mmol/L | Standard Deviation 0.24 |
Comparison: Within-group change from baseline to end point.p-value: 0.0018Wilcoxon signed rank test
p-value: 0.005Wilcoxon (Mann-Whitney)
Comparison: Within-group change from baseline to end point.p-value: 0.4454Wilcoxon signed rank test
Secondary
Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)
HOMA-IR is used to assess insulin resistance (IR). HOMA-IR is a dimensionless measure of insulin resistance (higher values present more insulin resistance. HOMA-IR are normalized so that lean, healthy individuals will have values of HOMA-IR close to 1.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR) | 0.28 dimensionless | Standard Deviation 5.39 |
| Olanzapine | Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR) | 0.43 dimensionless | Standard Deviation 5.37 |
p-value: 0.1117Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)
HOMA-%B is used to assess beta-cell function. HOMA-%B is a dimensionless measure of beta-cell function (higher values present increased insulin secretion for a given glucose level). HOMA-%B is normalized so that lean, healthy individuals will have values of HOMA-%B close to 100%.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B) | -7.54 dimensionless | Standard Deviation 85.91 |
| Olanzapine | Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B) | 18.82 dimensionless | Standard Deviation 147.63 |
p-value: 0.0325Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)
The level of low density lipoprotein cholesterol was calculated using the Friedwald QT formula.
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT) | -0.0029 mmol/L | Standard Deviation 0.6726 |
| Olanzapine | Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT) | 0.1892 mmol/L | Standard Deviation 0.7361 |
p-value: 0.0004Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Total Cholesterol
The total cholesterol level was assessed under fasted conditions.
Time frame: Baseline to End Point (up to 6 months)
Population: Safety data were analyzed using the Intent-to-Treat (ITT) analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Total Cholesterol | 0.0263 mmol/L | Standard Deviation 0.7841 |
| Olanzapine | Change From Baseline to End Point in Total Cholesterol | 0.2886 mmol/L | Standard Deviation 0.8493 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)
PANSS is an investigator-rated 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provided a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme).
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary endpoint analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS) | -13.50 points on a scale | Standard Deviation 15.86 |
| Olanzapine | Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS) | -16.60 points on a scale | Standard Deviation 15.02 |
p-value: 0.0242Schuirmann
Comparison: Within-group change from baseline to end point.p-value: <0.0001Wilcoxon signed rank test
Comparison: Within-group change from baseline to end point.p-value: <0.0001Wilcoxon signed rank test
Secondary
Change From Baseline to End Point in Triglycerides
The TG level was assessed under fasted conditions.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Change From Baseline to End Point in Triglycerides | -0.01 mmol/L | Standard Deviation 0.77 |
| Olanzapine | Change From Baseline to End Point in Triglycerides | 0.36 mmol/L | Standard Deviation 0.96 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Within-group change from baseline to end point.p-value: 0.9143Wilcoxon signed rank test
Comparison: Within-group change from baseline to end point.p-value: <0.0001Wilcoxon signed rank test
Secondary
Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up
Metabolic syndrome is defined according the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) of which 3 out of 5 criteria must be met: * waist circumference men \> 102 cm; waist circumference women \> 88 cm * TG ≥ 150 mg/dL * HDL cholesterol men \<40 mg/dL; HDL cholesterol women \<50 mg/dL * Blood pressure systolic ≥ 130 mmHg; Blood pressure diastolic ≥ 85 mmHg * Fasting glucose ≥ 110 mg /dL
Time frame: 6 months
Population: The secondary endpoint analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. In this case, the total number of patients in the analysis set depends on the number of patients without metabolic syndrome at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone ER | Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up | 23 Participants |
| Olanzapine | Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up | 38 Participants |
p-value: 0.023Fisher Exact
Secondary
Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up
Fasting plasma glucose ≥126 mg/dL or 2-hour post-load plasma glucose ≥200 mg/dL during an oral glucose tolerance test (OGTT) or initiated use of glucose-lowering agents during the course of the study.
Time frame: 6 months
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement.Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone ER | Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up | 21 Participants |
| Olanzapine | Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up | 23 Participants |
p-value: 0.6346Fisher Exact
Secondary
Number of Patients With Impaired Fasting Glucose
Post-baseline glucose level under fasted conditions ≥100 mg/dL but \<126 mg/dL.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone ER | Number of Patients With Impaired Fasting Glucose | 68 Participants |
| Olanzapine | Number of Patients With Impaired Fasting Glucose | 66 Participants |
p-value: 0.677Fisher Exact
Secondary
Number of Patients With Onset of Impaired Glucose Tolerance
Glucose ≥140 mg/dL, \<200 mg/dL after a 75g OGTT.
Time frame: Baseline to End Point (up to 6 months)
Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement.Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone ER | Number of Patients With Onset of Impaired Glucose Tolerance | 36 Participants |
| Olanzapine | Number of Patients With Onset of Impaired Glucose Tolerance | 33 Participants |
p-value: 1Fisher Exact