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

NCT ID: NCT00645099

Last Updated: 2014-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 462 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-04-30

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

001

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

Group Type: EXPERIMENTAL

paliperidone ER

Intervention Type: DRUG

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

002

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

Group Type: ACTIVE_COMPARATOR

olanzapine

Intervention Type: DRUG

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

Interventions

olanzapine

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

Intervention Type: DRUG

paliperidone ER

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag International NV Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag International NV

Locations

Buenos Aires, , Argentina

Córdoba, , Argentina

Mendoza, , Argentina

Alexandria, , Egypt

Cairo, , Egypt

El Banfaig 2 District, , Egypt

Pärnu, , Estonia

Tallinn, , Estonia

Tartu, , Estonia

Allonnes, , France

Bron, , France

Dijon, , France

Limoges, , France

Montberon, , France

Athens, , Greece

Amman, , Jordan

Jelgava, , Latvia

Liepāja, , Latvia

Riga, , Latvia

Sigulda, , Latvia

Strenči, , Latvia

Beirut, , Lebanon

Kaunas, , Lithuania

Vilnius, , Lithuania

Cluj-Napoca, , Romania

Craiova, , Romania

Oradea, , Romania

Sibiu, , Romania

Tg Mures, , Romania

Bratislava, , Slovakia

Michalovce, , Slovakia

Rimavská Sobota, , Slovakia

Cape Town, , South Africa

Johannesburg, , South Africa

A Coruña, , Spain

Alicante, , Spain

Barcelona, , Spain

Elche, , Spain

Madrid, , Spain

Santander, , Spain

Vic, , Spain

Zamora, , Spain

Ankara, , Turkey (Türkiye)

Bursa, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Manisa, , Turkey (Türkiye)

Countries

Argentina; Egypt; Estonia; France; Greece; Jordan; Latvia; Lebanon; Lithuania; Romania; Slovakia; South Africa; Spain; Turkey (Türkiye)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=50&filename=CR013189_CSR.pdf

A Prospective Randomized Open-label 6-Month Head-To-Head Trial to Compare Metabolic Effects of Paliperidone ER and Olanzapine in Subjects With Schizophrenia

Other Identifiers

R076477SCH3020

Identifier Type: -

Identifier Source: secondary_id

CR013189

Identifier Type: -

Identifier Source: org_study_id