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CompletedNCT00645099Updated May 8, 2014Results posted

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

A Phase 3 interventional study of olanzapine and paliperidone ER in Schizophrenia, sponsored by Janssen-Cilag International NV. Completed at 46 sites in 14 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2014-05-08.

Sponsored by Janssen-Cilag International NV · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
462
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Schizophrenia

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Keywords

  • Paliperidone ER
  • Olanzapine
  • Schizophrenia
03

In context

Schizophrenia

3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.

This study's enrollment of 462 is above the median of 70 across 2,872 interventional studies indexed under Schizophrenia.

Browse Schizophrenia studies →

Lead sponsor

Janssen-Cilag International NV is the lead sponsor of 66 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
462 participants (actual)

Study arms

  • Experimental
    001

    paliperidone ER 6-mg or 9-mg tablet once daily flexible dosing for 6 months

    Drug: paliperidone ER

  • Active comparator
    002

    olanzapine 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months

    Drug: olanzapine

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

06

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. Change From Baseline to End Point in Fasting Glucose

    Time frame: Baseline to End Point (up to 6 months)

  7. 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)

  8. 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)

  9. 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

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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

  18. 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)

07

Results

Posted Jul 29, 2010
Limitations and caveats
Open-label design

Participant flow

Participant flow — Overall Study
MilestonePaliperidone Extended Release (ER)Olanzapine
Started239220
Completed168178
Not completed7142
Withdrew: Lack of efficacy156
Withdrew: Withdrawal by subject3022
Withdrew: Lost to follow-up64
Withdrew: Adverse event115
Withdrew: Other95

Outcome measures

PrimaryChange 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)
Reported as:
Mean · Ratio
Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)
RatioPaliperidone EROlanzapine
Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)-0.08 ± 1.100.42 ± 1.19
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = < 0.0001This test was interpreted at the 5% significance level (2-tailed).
  • Paliperidone ER · Wilcoxon signed rank test · p = 0.4718This test was interpreted at the 5% significance level (2-tailed).
  • Olanzapine · Wilcoxon signed rank test · p = < 0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · mmol/L
Change From Baseline to End Point in Triglycerides
mmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in Triglycerides-0.01 ± 0.770.36 ± 0.96
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
  • Paliperidone ER · Wilcoxon signed rank test · p = 0.9143This test was interpreted at the 5% significance level (2-tailed).
  • Olanzapine · Wilcoxon signed rank test · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · mmol/L
Change From Baseline to End Point in High Density Lipoprotein
mmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in High Density Lipoprotein0.01 ± 0.25-0.04 ± 0.24
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.0050This test was interpreted at the 5% significance level (2-tailed).
  • Paliperidone ER · Wilcoxon signed rank test · p = 0.4454This test was interpreted at the 5% significance level (2-tailed).
  • Olanzapine · Wilcoxon signed rank test · p = 0.0018This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · mmol/L
Change From Baseline to End Point in Total Cholesterol
mmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in Total Cholesterol0.0263 ± 0.78410.2886 ± 0.8493
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · mmol/L
Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)
mmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)-0.0029 ± 0.67260.1892 ± 0.7361
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.0004This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · pmol/L
Change From Baseline to End Point in Converted Insulin
pmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in Converted Insulin2.7397 ± 89.977617.2327 ± 84.6255
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.0272This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange From Baseline to End Point in Fasting Glucose
Time frame:
Baseline to End Point (up to 6 months)
Reported as:
Mean · mmol/L
Change From Baseline to End Point in Fasting Glucose
mmol/LPaliperidone EROlanzapine
Change From Baseline to End Point in Fasting Glucose-0.2071 ± 0.49530.0769 ± 0.4781
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.1892This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · dimensionless
Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)
dimensionlessPaliperidone EROlanzapine
Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)-7.54 ± 85.9118.82 ± 147.63
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.0325This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · dimensionless
Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)
dimensionlessPaliperidone EROlanzapine
Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)0.28 ± 5.390.43 ± 5.37
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.1117This test was interpreted at the 5% significance level (2-tailed).
SecondaryNumber 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
Reported as:
Number · Participants
Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up
ParticipantsPaliperidone EROlanzapine
Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up2123
Statistical analysis
  • Paliperidone ER vs Olanzapine · Fisher Exact · p = 0.6346This test was interpreted at the 5% significance level (2-tailed).
SecondaryNumber 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)
Reported as:
Number · Participants
Number of Patients With Onset of Impaired Glucose Tolerance
ParticipantsPaliperidone EROlanzapine
Number of Patients With Onset of Impaired Glucose Tolerance3633
Statistical analysis
  • Paliperidone ER vs Olanzapine · Fisher Exact · p = 1.0000This test was interpreted at the 5% significance level (2-tailed).
SecondaryNumber 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)
Reported as:
Number · Participants
Number of Patients With Impaired Fasting Glucose
ParticipantsPaliperidone EROlanzapine
Number of Patients With Impaired Fasting Glucose6866
Statistical analysis
  • Paliperidone ER vs Olanzapine · Fisher Exact · p = 0.6770This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · pM/mM
Change From Baseline at End Point of the Insulinogenic Index
pM/mMPaliperidone EROlanzapine
Change From Baseline at End Point of the Insulinogenic Index2.21 ± 173.4633.78 ± 259.56
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.1308This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · pM/mM
Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin
pM/mMPaliperidone EROlanzapine
Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin8.63 ± 79.5317.28 ± 94.51
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = 0.3358This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · kg
Change From Baseline at End Point in Body Weight
kgPaliperidone EROlanzapine
Change From Baseline at End Point in Body Weight1.16 ± 4.573.81 ± 5.87
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
  • Paliperidone ER · Wilcoxon signed rank test · p = 0.0001This test was interpreted at the 5% significance level (2-tailed).
  • Olanzapine · Wilcoxon signed rank test · p = < 0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · kg/m²
Change From Baseline at End Point in Body Mass Index (BMI)
kg/m²Paliperidone EROlanzapine
Change From Baseline at End Point in Body Mass Index (BMI)0.43 ± 1.591.32 ± 1.99
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · cm
Change From Baseline at End Point in Waist Circumference
cmPaliperidone EROlanzapine
Change From Baseline at End Point in Waist Circumference0.70 ± 5.393.38 ± 6.18
Statistical analysis
  • Paliperidone ER vs Olanzapine · Wilcoxon (Mann-Whitney) · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
SecondaryNumber 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
Reported as:
Number · Participants
Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up
ParticipantsPaliperidone EROlanzapine
Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up2338
Statistical analysis
  • Paliperidone ER vs Olanzapine · Fisher Exact · p = 0.0230This test was interpreted at the 5% significance level (2-tailed).
SecondaryChange 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)
Reported as:
Mean · points on a scale
Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)
points on a scalePaliperidone EROlanzapine
Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)-13.50 ± 15.86-16.60 ± 15.02
Statistical analysis
  • Paliperidone ER vs Olanzapine · Schuirmann · p = 0.0242The null hypothesis of non-equivalence was rejected and equivalence to within the specified equivalence bounds could be claimed.
  • Paliperidone ER · Wilcoxon signed rank test · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).
  • Olanzapine · Wilcoxon signed rank test · p = <0.0001This test was interpreted at the 5% significance level (2-tailed).

Adverse events

Collected over 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.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Paliperidone ER—21/239 (8.8%)98/239 (41%)
Olanzapine—12/220 (5.5%)93/220 (42.3%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventPaliperidone EROlanzapine
SchizophreniaPsychiatric disorders8/2393/220
Psychotic disorderPsychiatric disorders6/2391/220
Psychiatric decompensationPsychiatric disorders0/2392/220
DepressionPsychiatric disorders2/2390/220
LeukopeniaBlood and lymphatic system disorders2/2390/220
Psychiatric symptomPsychiatric disorders1/2391/220
NervousnessPsychiatric disorders0/2391/220
Schizophrenia, paranoid typePsychiatric disorders0/2391/220
Suicide attemptPsychiatric disorders0/2391/220
MastitisInfections and infestations0/2391/220
Most frequent other events
Showing 10 of 35
Most frequent other events
EventPaliperidone EROlanzapine
Weight increasedInvestigations23/23940/220
InsomniaPsychiatric disorders23/2393/220
SomnolenceNervous system disorders8/23921/220
HeadacheNervous system disorders11/2399/220
AnxietyPsychiatric disorders10/2393/220
AmenorrhoeaReproductive system and breast disorders8/2390/220
Blood creatine phosphokinase increasedInvestigations7/2395/220
SedationNervous system disorders5/2396/220
AkathisiaNervous system disorders6/2392/220
Increased appetiteMetabolism and nutrition disorders4/2395/220

Baseline characteristics

Age, Continuous
Age, Continuous(years)Paliperidone EROlanzapineTotal
Mean38.8 ± 11.137.5 ± 11.438.2 ± 11.2
Sex: Female, Male
Sex: Female, Male(Participants)Paliperidone EROlanzapineTotal
Female10687193
Male133133266
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m²)Paliperidone EROlanzapineTotal
Mean26.9 ± 6.3127.0 ± 5.7326.9 ± 6.03
Waist
Waist(cm)Paliperidone EROlanzapineTotal
Mean92.2 ± 14.493.3 ± 15.692.7 ± 14.9
Weight
Weight(kg)Paliperidone EROlanzapineTotal
Mean75.9 ± 17.077.9 ± 16.576.9 ± 16.8
08

Study locations

46 sites
  • Buenos Aires, Argentina
  • Cordoba, Argentina
  • Mendoza, Argentina
  • Alexandria, Egypt
  • Cairo, Egypt
  • El Banfaig 2 District, Egypt
  • Pärnu N/A, Estonia
  • Tallinn, Estonia
  • Tartu N/A, Estonia
  • Allonnes, France
  • Bron, France
  • Dijon, France
  • Limoges Cedex 1, France
  • Montberon, France
  • Athens, Greece
  • Amman, Jordan
  • Jelgava, Latvia
  • Liepaja, Latvia
  • Riga, Latvia
  • Sigulda, Latvia
  • Strenci, Latvia
  • Beirut, Lebanon
  • Kaunas, Lithuania
  • Vilnius, Lithuania
  • Cluj-Napoca, Romania
  • Craiova, Romania
  • Oradea, Romania
  • Sibiu, Romania
  • Tg Mures, Romania
  • Bratislava, Slovakia
  • Michalovce, Slovakia
  • Rimavska Sobota, Slovakia
  • Cape Town, South Africa
  • Johannesburg, South Africa
  • Alicante, Spain
  • Barcelona, Spain
  • Coruña, Spain
  • Elche, Spain
  • Madrid, Spain
  • Santander, Spain
  • Vic, Spain
  • Zamora, Spain
  • Ankara, Turkey
  • Bursa, Turkey
  • Istanbul, Turkey
  • Manisa, Turkey
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 8, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00645099
Lead sponsor
Janssen-Cilag International NV
Responsible party
Sponsor
First posted
Mar 27, 2008
Start date
Oct 2007
Primary completion
Apr 2009
Completion
Apr 2009
Results posted
Jul 29, 2010
Last update
May 8, 2014

Study contacts

Janssen-Cilag International NV Clinical Trial
study director · Janssen-Cilag International NV

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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