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SchizophreniaPhase 3NCT00645099

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

A Phase 3 study testing olanzapine and paliperidone ER in people with Schizophrenia, run by Janssen-Cilag International NV at 46 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Schizophrenia
What is being tested?
olanzapine and paliperidone ER
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
462 participants
Where
46 sitesin 14 countries
Study dates
Oct 2007to Apr 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

46 sites in 14 countries.

46 sites in 14 countries

Spain8 sites

  • Study site

    A Coruña

  • Study site

    Alicante

  • Study site

    Barcelona

  • Study site

    Elche

  • Study site

    Madrid

  • Study site

    Santander

  • Study site

    Vic

  • Study site

    Zamora

Other trials in Spain

France5 sites

  • Study site

    Allonnes

  • Study site

    Bron

  • Study site

    Dijon

  • Study site

    Limoges

  • Study site

    Montberon

Other trials in France

Latvia5 sites

  • Study site

    Jelgava

  • Study site

    Liepāja

  • Study site

    Riga

  • Study site

    Sigulda

  • Study site

    Strenči

Other trials in Latvia

Romania5 sites

  • Study site

    Cluj-Napoca

  • Study site

    Craiova

  • Study site

    Oradea

  • Study site

    Sibiu

  • Study site

    Tg Mures

Other trials in Romania

Turkey (Türkiye)4 sites

  • Study site

    Ankara

  • Study site

    Bursa

  • Study site

    Istanbul

  • Study site

    Manisa

Other trials in Turkey (Türkiye)

Argentina3 sites

  • Study site

    Buenos Aires

  • Study site

    Córdoba

  • Study site

    Mendoza

Other trials in Argentina

Egypt3 sites

  • Study site

    Alexandria

  • Study site

    Cairo

  • Study site

    El Banfaig 2 District

Other trials in Egypt

Estonia3 sites

  • Study site

    Pärnu

  • Study site

    Tallinn

  • Study site

    Tartu

Other trials in Estonia

Slovakia3 sites

  • Study site

    Bratislava

  • Study site

    Michalovce

  • Study site

    Rimavská Sobota

Other trials in Slovakia

Lithuania2 sites

  • Study site

    Kaunas

  • Study site

    Vilnius

Other trials in Lithuania

South Africa2 sites

  • Study site

    Cape Town

  • Study site

    Johannesburg

Other trials in South Africa

Greece1 site

  • Study site

    Athens

Other trials in Greece

Jordan1 site

  • Study site

    Amman

Other trials in Jordan

Lebanon1 site

  • Study site

    Beirut

Other trials in Lebanon

About this study

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

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.

Conditions
Schizophrenia
Being tested
olanzapine, paliperidone ER
Keywords
Paliperidone ER, Olanzapine, Schizophrenia
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • olanzapineDrug

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

  • paliperidone ERDrug

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

Study groups in NCT00645099
Study groupRoleWhat they receive
001Experimentalpaliperidone ER 6-mg or 9-mg tablet once daily flexible dosing for 6 months
Receives: Drug: paliperidone ER
002Active comparatorolanzapine 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Receives: Drug: olanzapine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to End Point (up to 6 months)

Secondary outcomes (18)

  1. Change From Baseline to End Point in Triglycerides

    The TG level was assessed under fasted conditions.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: Baseline to End Point (up to 6 months)

  6. Change From Baseline to End Point in Fasting Glucose

    Measured: 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%.

    Measured: 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.

    Measured: 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.

    Measured: 6 months

  10. Number of Patients With Onset of Impaired Glucose Tolerance

    Glucose ≥140 mg/dL, <200 mg/dL after a 75g OGTT.

    Measured: 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.

    Measured: 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).

    Measured: 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.).

    Measured: 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.

    Measured: 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).

    Measured: 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.

    Measured: 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

    Measured: 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).

    Measured: Baseline to End Point (up to 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2008 (estimated)
  2. Study startOct 2007
  3. Primary completionApr 2009
  4. Study completionApr 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
462 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00645099
Sponsor's protocol ID
CR013189
Other IDs
R076477SCH3020
Status last verified
Apr 2014
First submitted
24 Mar 2008
Last updated
8 May 2014
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing olanzapine and paliperidone ER in people with Schizophrenia, run by Janssen-Cilag International NV at 46 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Spain, France, Latvia, Romania, Turkey (Türkiye) and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio) (time frame: Baseline to End Point (up to 6 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00645099.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2014.

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