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A 6 Month Study to Compare the Metabolic Effects of Paliperidone ER and Olanzapine in Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00645099
Recruitment Status : Completed
First Posted : March 27, 2008
Results First Posted : July 29, 2010
Last Update Posted : May 8, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: olanzapine
Drug: paliperidone ER
Enrollment 462
Recruitment Details  
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.
Arm/Group Title Paliperidone Extended Release (ER) Olanzapine
Hide Arm/Group Description 6-mg or 9-mg tablet once daily flexible dosing for 6 months 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Period Title: Overall Study
Started 239 220
Completed 168 178
Not Completed 71 42
Reason Not Completed
Lack of Efficacy             15             6
Withdrawal by Subject             30             22
Lost to Follow-up             6             4
Adverse Event             11             5
Other             9             5
Arm/Group Title Paliperidone ER Olanzapine Total
Hide Arm/Group Description 6-mg or 9-mg tablet once daily flexible dosing for 6 months 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months Total of all reporting groups
Overall Number of Baseline Participants 239 220 459
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 239 participants 220 participants 459 participants
38.8  (11.1) 37.5  (11.4) 38.2  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 239 participants 220 participants 459 participants
Female
106
  44.4%
87
  39.5%
193
  42.0%
Male
133
  55.6%
133
  60.5%
266
  58.0%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m²
Number Analyzed 239 participants 220 participants 459 participants
26.9  (6.31) 27.0  (5.73) 26.9  (6.03)
Waist  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 239 participants 220 participants 459 participants
92.2  (14.4) 93.3  (15.6) 92.7  (14.9)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 239 participants 220 participants 459 participants
75.9  (17.0) 77.9  (16.5) 76.9  (16.8)
1.Primary Outcome
Title Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)
Hide Description Plasma fasting TG and HDL concentrations were measured to determine the TG:HDL ratio.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 215 198
Mean (Standard Deviation)
Unit of Measure: Ratio
-0.08  (1.10) 0.42  (1.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments 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).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone ER
Comments Within-group comparison of the change from baseline at end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4718
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Olanzapine
Comments Within-group change from baseline at end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
2.Secondary Outcome
Title Change From Baseline to End Point in Triglycerides
Hide Description The TG level was assessed under fasted conditions.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 223 203
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.01  (0.77) 0.36  (0.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone ER
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9143
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Olanzapine
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
3.Secondary Outcome
Title Change From Baseline to End Point in High Density Lipoprotein
Hide Description The HDL level was assessed under fasted conditions.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 216 198
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.01  (0.25) -0.04  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone ER
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4454
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Olanzapine
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
4.Secondary Outcome
Title Change From Baseline to End Point in Total Cholesterol
Hide Description The total cholesterol level was assessed under fasted conditions.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 223 203
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.0263  (0.7841) 0.2886  (0.8493)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
5.Secondary Outcome
Title Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)
Hide Description The level of low density lipoprotein cholesterol was calculated using the Friedwald QT formula.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 216 194
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.0029  (0.6726) 0.1892  (0.7361)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
6.Secondary Outcome
Title Change From Baseline to End Point in Converted Insulin
Hide Description The insulin level was assessed under fasted conditions.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 209 182
Mean (Standard Deviation)
Unit of Measure: pmol/L
2.7397  (89.9776) 17.2327  (84.6255)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0272
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
7.Secondary Outcome
Title Change From Baseline to End Point in Fasting Glucose
Hide Description [Not Specified]
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 14 13
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.2071  (0.4953) 0.0769  (0.4781)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1892
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
8.Secondary Outcome
Title Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 183 174
Mean (Standard Deviation)
Unit of Measure: dimensionless
-7.54  (85.91) 18.82  (147.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0325
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
9.Secondary Outcome
Title Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 184 174
Mean (Standard Deviation)
Unit of Measure: dimensionless
0.28  (5.39) 0.43  (5.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1117
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
10.Secondary Outcome
Title Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 239 220
Measure Type: Number
Unit of Measure: Participants
21 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6346
Comments [Not Specified]
Method Fisher Exact
Comments This test was interpreted at the 5% significance level (2-tailed).
11.Secondary Outcome
Title Number of Patients With Onset of Impaired Glucose Tolerance
Hide Description Glucose ≥140 mg/dL, <200 mg/dL after a 75g OGTT.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 217 198
Measure Type: Number
Unit of Measure: Participants
36 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Fisher Exact
Comments This test was interpreted at the 5% significance level (2-tailed).
12.Secondary Outcome
Title Number of Patients With Impaired Fasting Glucose
Hide Description Post-baseline glucose level under fasted conditions ≥100 mg/dL but <126 mg/dL.
Time Frame Baseline to End Point (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 223 203
Measure Type: Number
Unit of Measure: Participants
68 66
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6770
Comments [Not Specified]
Method Fisher Exact
Comments This test was interpreted at the 5% significance level (2-tailed).
13.Secondary Outcome
Title Change From Baseline at End Point of the Insulinogenic Index
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 154 147
Mean (Standard Deviation)
Unit of Measure: pM/mM
2.21  (173.46) 33.78  (259.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1308
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
14.Secondary Outcome
Title Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 183 169
Mean (Standard Deviation)
Unit of Measure: pM/mM
8.63  (79.53) 17.28  (94.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3358
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
15.Secondary Outcome
Title Change From Baseline at End Point in Body Weight
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 235 214
Mean (Standard Deviation)
Unit of Measure: kg
1.16  (4.57) 3.81  (5.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone ER
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Olanzapine
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
16.Secondary Outcome
Title Change From Baseline at End Point in Body Mass Index (BMI)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 235 214
Mean (Standard Deviation)
Unit of Measure: kg/m²
0.43  (1.59) 1.32  (1.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
17.Secondary Outcome
Title Change From Baseline at End Point in Waist Circumference
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 231 213
Mean (Standard Deviation)
Unit of Measure: cm
0.70  (5.39) 3.38  (6.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments This test was interpreted at the 5% significance level (2-tailed).
18.Secondary Outcome
Title Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 174 163
Measure Type: Number
Unit of Measure: Participants
23 38
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0230
Comments [Not Specified]
Method Fisher Exact
Comments This test was interpreted at the 5% significance level (2-tailed).
19.Secondary Outcome
Title Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description:
6-mg or 9-mg tablet once daily flexible dosing for 6 months
10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Number of Participants Analyzed 234 214
Mean (Standard Deviation)
Unit of Measure: points on a scale
-13.50  (15.86) -16.60  (15.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone ER, Olanzapine
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Testing non-inferiority of the paliperidone ER treatment group compared to the olanzapine treatment group, with regard to change versus baseline at end point of the total PANSS was done by means of Schuirmann’s test. A difference of 6 points in change versus baseline on the total PANSS was considered to be a minimum clinically relevant difference.The null hypothesis is that there is no difference between paliperidone and olanzapine in change in TG:HDL ratio from baseline to endpoint.
Statistical Test of Hypothesis P-Value 0.0242
Comments [Not Specified]
Method Schuirmann
Comments The null hypothesis of non-equivalence was rejected and equivalence to within the specified equivalence bounds could be claimed.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone ER
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Olanzapine
Comments Within-group change from baseline to end point.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon signed rank test
Comments This test was interpreted at the 5% significance level (2-tailed).
Time Frame From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paliperidone ER Olanzapine
Hide Arm/Group Description 6-mg or 9-mg tablet once daily flexible dosing for 6 months 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
All-Cause Mortality
Paliperidone ER Olanzapine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paliperidone ER Olanzapine
Affected / at Risk (%) Affected / at Risk (%)
Total   21/239 (8.79%)   12/220 (5.45%) 
Blood and lymphatic system disorders     
Leukopenia * 1  2/239 (0.84%)  0/220 (0.00%) 
Agranulocytosis * 1  1/239 (0.42%)  0/220 (0.00%) 
Neutropenia * 1  1/239 (0.42%)  0/220 (0.00%) 
Gastrointestinal disorders     
Duodenal ulcer haemorrhage * 1  1/239 (0.42%)  0/220 (0.00%) 
General disorders     
Asthenia * 1  1/239 (0.42%)  0/220 (0.00%) 
Fatigue * 1  1/239 (0.42%)  0/220 (0.00%) 
Infections and infestations     
Mastitis * 1  0/239 (0.00%)  1/220 (0.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma * 1  0/239 (0.00%)  1/220 (0.45%) 
Psychiatric disorders     
Schizophrenia * 1  8/239 (3.35%)  3/220 (1.36%) 
Psychotic disorder * 1  6/239 (2.51%)  1/220 (0.45%) 
Depression * 1  2/239 (0.84%)  0/220 (0.00%) 
Psychiatric decompensation * 1  0/239 (0.00%)  2/220 (0.91%) 
Psychiatric symptom * 1  1/239 (0.42%)  1/220 (0.45%) 
Intentional self-injury * 1  1/239 (0.42%)  0/220 (0.00%) 
Nervousness * 1  0/239 (0.00%)  1/220 (0.45%) 
Schizophrenia, paranoid type * 1  0/239 (0.00%)  1/220 (0.45%) 
Suicide attempt * 1  0/239 (0.00%)  1/220 (0.45%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  1/239 (0.42%)  0/220 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Paliperidone ER Olanzapine
Affected / at Risk (%) Affected / at Risk (%)
Total   98/239 (41.00%)   93/220 (42.27%) 
Gastrointestinal disorders     
Dyspepsia * 1  4/239 (1.67%)  2/220 (0.91%) 
Nausea * 1  3/239 (1.26%)  1/220 (0.45%) 
General disorders     
Fatigue * 1  5/239 (2.09%)  2/220 (0.91%) 
Irritability * 1  3/239 (1.26%)  3/220 (1.36%) 
Infections and infestations     
Influenza * 1  2/239 (0.84%)  3/220 (1.36%) 
Nasopharyngitis * 1  3/239 (1.26%)  1/220 (0.45%) 
Urinary tract infection * 1  3/239 (1.26%)  0/220 (0.00%) 
Investigations     
Weight increased * 1  23/239 (9.62%)  40/220 (18.18%) 
Blood creatine phosphokinase increased * 1  7/239 (2.93%)  5/220 (2.27%) 
Alanine aminotransferase increased * 1  1/239 (0.42%)  3/220 (1.36%) 
Blood glucose increased * 1  1/239 (0.42%)  3/220 (1.36%) 
Gamma-glutamyltransferase increased * 1  1/239 (0.42%)  3/220 (1.36%) 
Waist circumference increased * 1  0/239 (0.00%)  4/220 (1.82%) 
Weight decreased * 1  3/239 (1.26%)  1/220 (0.45%) 
Blood triglycerides increased * 1  0/239 (0.00%)  3/220 (1.36%) 
Metabolism and nutrition disorders     
Increased appetite * 1  4/239 (1.67%)  5/220 (2.27%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal stiffness * 1  3/239 (1.26%)  0/220 (0.00%) 
Nervous system disorders     
Somnolence * 1  8/239 (3.35%)  21/220 (9.55%) 
Headache * 1  11/239 (4.60%)  9/220 (4.09%) 
Sedation * 1  5/239 (2.09%)  6/220 (2.73%) 
Akathisia * 1  6/239 (2.51%)  2/220 (0.91%) 
Dizziness * 1  5/239 (2.09%)  2/220 (0.91%) 
Dyskinesia * 1  3/239 (1.26%)  2/220 (0.91%) 
Hypersomnia * 1  3/239 (1.26%)  2/220 (0.91%) 
Psychiatric disorders     
Insomnia * 1  23/239 (9.62%)  3/220 (1.36%) 
Anxiety * 1  10/239 (4.18%)  3/220 (1.36%) 
Tension * 1  5/239 (2.09%)  1/220 (0.45%) 
Agitation * 1  4/239 (1.67%)  1/220 (0.45%) 
Schizophrenia * 1  4/239 (1.67%)  1/220 (0.45%) 
Psychotic disorder * 1  3/239 (1.26%)  1/220 (0.45%) 
Restlessness * 1  3/239 (1.26%)  1/220 (0.45%) 
Depression * 1  0/239 (0.00%)  3/220 (1.36%) 
Reproductive system and breast disorders     
Amenorrhoea * 1  8/239 (3.35%)  0/220 (0.00%) 
Galactorrhoea * 1  3/239 (1.26%)  0/220 (0.00%) 
Vascular disorders     
Hypertension * 1  2/239 (0.84%)  3/220 (1.36%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: EMEA Therapeutic Area Leader CNS
Organization: Janssen-Cilag Germany
Phone: +492137955153
Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00645099     History of Changes
Other Study ID Numbers: CR013189
R076477SCH3020
First Submitted: March 24, 2008
First Posted: March 27, 2008
Results First Submitted: April 7, 2010
Results First Posted: July 29, 2010
Last Update Posted: May 8, 2014