Clinical trial NCT00645099: A 6 Month Study to Compare the Metabolic Effects of Paliperidone ER and Olanzapine in Patients With Schizophrenia
Official title: A Prospective Randomized Open-label 6-Month Head-To-Head Trial to Compare Metabolic Effects of Paliperidone ER and Olanzapine in Subjects With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Paliperidone ER
Olanzapine
Schizophrenia
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2008-03-27
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)
timeFrame: Baseline to End Point (up to 6 months)
Secondary outcomes:
measure: Change From Baseline to End Point in Triglycerides
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in High Density Lipoprotein
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Total Cholesterol
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Converted Insulin
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Fasting Glucose
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline to End Point (up to 6 months)
measure: Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up
timeFrame: 6 months
measure: Number of Patients With Onset of Impaired Glucose Tolerance
timeFrame: Baseline to End Point (up to 6 months)
measure: Number of Patients With Impaired Fasting Glucose
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline at End Point of the Insulinogenic Index
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline at End Point in Body Weight
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline at End Point in Body Mass Index (BMI)
timeFrame: Baseline to End Point (up to 6 months)
measure: Change From Baseline at End Point in Waist Circumference
timeFrame: Baseline to End Point (up to 6 months)
measure: Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up
timeFrame: 6 months
measure: Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)
timeFrame: Baseline to End Point (up to 6 months)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Mendoza
country: Argentina
city: Alexandria
country: Egypt
city: Cairo
country: Egypt
city: El Banfaig 2 District
country: Egypt
city: Pärnu N/A
country: Estonia
city: Tallinn
country: Estonia
city: Tartu N/A
country: Estonia
city: Allonnes
country: France
city: Bron
country: France
city: Dijon
country: France
city: Limoges Cedex 1
country: France
city: Montberon
country: France
city: Athens
country: Greece
city: Amman
country: Jordan
city: Jelgava
country: Latvia
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Sigulda
country: Latvia
city: Strenci
country: Latvia
city: Beirut
country: Lebanon
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Cluj-Napoca
country: Romania
city: Craiova
country: Romania
city: Oradea
country: Romania
city: Sibiu
country: Romania
city: Tg Mures
country: Romania
city: Bratislava
country: Slovakia
city: Michalovce
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Cape Town
country: South Africa
city: Johannesburg
country: South Africa
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Coruña
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Vic
country: Spain
city: Zamora
country: Spain
city: Ankara
country: Turkey
city: Bursa
country: Turkey
city: Istanbul
country: Turkey
city: Manisa
country: Turkey
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: