A Randomized, Double-Blind, Parallel-Group, Comparative Study of Flexible Doses of Paliperidone Palmitate and Flexible Doses of Risperidone Long-Acting Intramuscular Injection in Subjects with Schizophrenia

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-003560-62-BG
• Date of registration: 18/04/2008
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V., Turnhoutseweg 30, 2340 Beerse, Belgium
• Public title: A Randomized, Double-Blind, Parallel-Group, Comparative Study of Flexible Doses of Paliperidone Palmitate and Flexible Doses of Risperidone Long-Acting Intramuscular Injection in Subjects with Schizophrenia
• Scientific title: A Randomized, Double-Blind, Parallel-Group, Comparative Study of Flexible Doses of Paliperidone Palmitate and Flexible Doses of Risperidone Long-Acting Intramuscular Injection in Subjects with Schizophrenia
• Date of first enrolment: 22/04/2008
• Target sample size: 1050
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003560-62
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Bulgaria, Czech Republic, Estonia, France, Germany, Hungary, Lithuania, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Men or women, aged at least 18 years old or the minimum age to provide
informed consent in the jurisdiction in which the study is taking place,
whichever is greater

Meet diagnostic criteria for schizophrenia according to DSM-IV
(disorganized type [295.10], catatonic type [295.20], paranoid type
[295.30], residual type [295.60], or undifferentiated type [295.90]) for at
least 1 year before screening

A total PANSS score between 60 and 120, inclusive, at screening and
baseline

Body mass index (BMI) at the screening visit BMI .17 kg/m2

Female subjects must be postmenopausal for at least 2 years, surgically
sterile, abstinent, or, if sexually active, be practicing an effective method
of birth control before study entry and throughout the study. Effective
methods of birth control include contraceptive pills, coil, depot injection
of gestagen, subdermal implantation, hormonal vaginal ring, and
transdermal depot patches. Women of childbearing potential must have a
negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy
test result at screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Unable to provide their own consent or involuntarily committed to
psychiatric hospitalization

A primary, active DSM-IV diagnosis on Axis I other than schizophrenia

A DSM-IV diagnosis of active substance dependence within 3 months
before screening (nicotine and caffeine are not exclusionary)

History of treatment resistance as defined by failure to respond to
2 adequate treatments with different antipsychotic medications (an
adequate treatment is defined as a minimum of 6 weeks at maximum
tolerated dosage)

Relevant history or current presence of any significant or unstable
cardiovascular, respiratory, neurologic (including seizures or significant
cerebrovascular disease), renal, hepatic, hematologic, endocrine,
immunologic, morbid obesity (BMI >40 kg/m2), or other systemic disease

History of any severe pre-existing gastrointestinal narrowing (pathologic
or iatrogenic) or inability to swallow oral study drug whole with the aid of
water (applies to those subjects requiring oral tolerability only)

Serum chemistry, hematology, or urinalysis results that are not within the
laboratory’s normal reference range and are deemed to be clinically
significant by the investigator

History or evidence of clinically significant hepatic disease [including
aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
>2 times the upper limit of normal] at screening


History of neuroleptic malignant syndrome (NMS)

Significant risk of suicidal or violent behavior, as clinically assessed by
the investigator

Subjects who have participated in 2 or more clinical trials in the past year,
or in 1 clinical trial in the past 6 months (non-intervention, observational,
and retrospective studies excluded)

History of any active malignancy within previous 5 years, with the exception of basal cell carcinomas.

Women who are pregnant or nursing, or is planning to become pregnant during the trial.

Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of the investigator or study center, as well as family members of the employees or the investigator

History of disallowed therapies:
An injectable antipsychotic within 1 injection interval before screening.
clozapine within 3 months before baseline
Risperidone LAI injection within 6 weeks before screeningprevious injection of paliperidone palmitate within past 10 months
Electroconvulsive therapy (ECT) within 60 days before screening
Nonselective/irreversible MAOI antidepressants within 30 days before screening

The following types of medications are not permitted during the double blind and should be washed out by Day –1, (protocol guideline for washout is 5 times the elimination half life):

Mood stabilizers, including lithium and all anticonvulsants
Antiparkinsonian medication
Beta Blockers
other prescription, OTC or herbal agents with psychoactive properties

History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death in association with the use of drugs that prolong the QTc interval, including:

Heart rate <50 beats per minute
Demonstration of repeated prolonged QTc Fridericia interval >450 ms,as measured on more than one ECG (either during screening, or from prior medical records)
The following cardiac conditions: sick sinus syndrome, complete atrioventricular block, congestive heart failure, polymorphic ventricular tachycardia
Clinically relevant hypocalcemia, hypokalem

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Schizophrenia
MedDRA version: 9.1 Level: LLT Classification code 10039626 Term: Schizophrenia

Intervention(s)

Trade Name: INVEGA
Product Name: Paliperidone OROS 6mg extended release (ER) system
Product Code: F040
Pharmaceutical Form: Tablet
INN or Proposed INN: Paliperidone
CAS Number: 144598-75-4
Current Sponsor code: R076477
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-

Product Name: Paliperidone Palmitate 100mg/ml nano suspension
Product Code: R092670 (F013)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Paliperidone Palmitate
CAS Number: 144598-75-4
Current Sponsor code: R092670
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: Risperdal 1mg Tablets
Product Code: F005
Pharmaceutical Form: Tablet
INN or Proposed INN: Risperidone
CAS Number: 106266-06-2
Current Sponsor code: R064766
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Risperdal CONSTA 25mg
Product Code: F109
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Risperidone
CAS Number: 106266-06-2
Current Sponsor code: R064766
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: Risperdal Consta 37.5mg
Product Code: F109
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Risperidone
CAS Number: 106266-06-2
Current Sponsor code: R064766
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 37.5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: Risperidone CONSTA 50 mg
Product Code: F109
Pharmaceutical Form: Suspension for injection
INN or

Primary Outcome(s)

Primary end point(s): The primary endpoint is the change from baseline to endpoint in the total
PANSS score. The change from the baseline score at each visit and at
endpoint will be analyzed using an analysis of covariance (ANCOVA)
model with factors for treatment and investigator, and baseline PANSS total
score as the covariate. The point estimate and 2-sided 95% confidence
interval based on ANCOVA will be provided for the difference between
risperidone LAI and paliperidone palmitate in the mean change from
baseline in total PANSS score. Noninferiority of paliperidone palmitate to
risperidone LAI will be concluded if the lower limit of the 2-sided
95% confidence interval exceeds –5.

In addition to the per-protocol analysis set, additional analyses with the
intent-to-treat analysis set (all randomized subjects who received at least
1 dose of double-blind study drug and have at least 1 efficacy measurement
during the double-blind treatment period) will be performed to evaluate
consistency of results.

Main Objective: The primary objective of this study is to demonstrate that paliperidone
palmitate is not less effective than risperidone LAI. The safety and
tolerability of paliperidone palmitate in the treatment of schizophrenia will
also be assessed.

Secondary Objective: Assessment of the global improvement in severity of illness associated
with the use of paliperidone palmitate compared with risperidone LAI

Explore the effects to personal and social functioning associated with the
use of paliperidone palmitate compared with risperidone LAI

Explore the effects of paliperidone palmitate compared with risperidone
LAI in improvement of sleep quality and reduction of daytime sleepiness

Secondary ID(s)

R092670PSY3006

2006-003560-62-HU