Comparison of Paliperidone Palmitate and RISPERDAL CONSTA... | NCT00589914

ID	Type	Description	Link
R092670PSY3006	Other Identifier	Unique Protocol Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
RISPERDAL CONSTA	Active Comparator	RISPERDAL CONSTA 25-50 mg eq every 2 weeks	Drug: RISPERDAL CONSTA
R092670	Experimental	Paliperidone Palmitate 50-150 mg eq every 4 wks	Drug: Paliperidone palmitate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
RISPERDAL CONSTA	Drug	RISPERDAL CONSTA: Type=exact number, unit=mg, number=25, 37.5, or 50, form=suspension for injection, route=Intramuscular use. One i.m. injection of RISPERDAL CONSTA 25-50 mg eq every 2 weeks at V4, V6, V7, V8, V9, and V10. PALIPERIDONE PALMITATE PLACEBO: Form=suspension for injection, route=Intramuscular use. One i.m. injection every 2 weeks at Baseline and at V4, V7, and V9. RISPERIDONE: Type=up to, unit=mg, number=1 to 6, form=Tablet, route=Oral Use. One tablet for the first 4 weeks (28 days) of the DB treatment period.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in the Positive and Negative Syndrome Scale (PANSS) Total Score for Schizophrenia	The PANSS scale is used to assess the neuropsychiatric symptoms of schizophrenia. The 30-item PANSS scale provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items),and the general psychopathology subscale (16 items), each item rated on a scale of 1 (absent) to 7 (extreme).	Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)

Secondary Outcomes

Measure	Description	Time Frame
The Change From Baseline for the CGI-S Score	The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the patient's condition at a given time. A qualified rater administered the CGI-S.	Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)]

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Meet diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria as specified by the protocol for at least 1 year before screening
Prior medical records, written documentation or verbal information obtained from previous psychiatric providers obtained by the investigator must be consistent with the diagnosis of schizophrenia
A total PANSS score between 60 and 120, inclusive, at screening and baseline; Body mass index (BMI) at the screening visit BMI at least 17 kg/m2
Female patients 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 as specified by the protocol. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (b hCG) pregnancy test result at screening.

Exclusion Criteria:

Patient unable to provide 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, or other systemic disease including history of neuroleptic malignant syndrome; History of any severe pre-existing gastrointestinal narrowing or inability to swallow oral study drug whole with the aid of water (applies to those patients requiring oral tolerability only)
Significant risk of suicidal or violent behavior, as clinically assessed by the investigator ; History of life-threatening allergic reaction to any drug; Known or suspected hypersensitivity or intolerance to risperidone, paliperidone, 20% Intralipid, or any of their excipients (e.g., soybean oil, egg yolks, phospholipids, and glycerol)
Have received an experimental drug or experimental biologic, or used an experimental medical device within 6 months before screening; History of any active malignancy within the previous 5 years, with the exception of basal cell carcinomas
Women who are pregnant or breast-feeding or are planning to become pregnant uring the study

Name	Affiliation	Role
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24754314	Derived	Alphs L, Bossie CA, Fu DJ, Ma YW, Kern Sliwa J. Onset and persistence of efficacy by symptom domain with long-acting injectable paliperidone palmitate in patients with schizophrenia. Expert Opin Pharmacother. 2014 May;15(7):1029-42. doi: 10.1517/14656566.2014.909409.
24113628	Derived	Fu DJ, Bossie CA, Sliwa JK, Ma YW, Alphs L. Paliperidone palmitate versus oral risperidone and risperidone long-acting injection in patients with recently diagnosed schizophrenia: a tolerability and efficacy comparison. Int Clin Psychopharmacol. 2014 Jan;29(1):45-55. doi: 10.1097/YIC.0000000000000006.

Label	URL
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	View source

ID	Title	Description
FG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
FG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).

Categories

Title	Measurements
<=18 years	BG0003 BG0012 BG0025
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00039± 12.13 BG00138.7± 11.83 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000245 BG001268 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Austria

Title	Measurements
	BG0003 BG0013 BG002

AgeCategorical

Number

participants

Title

Denominators

Categories

18-25 years

Title	Measurements
	BG000103 BG00192 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in the Positive and Negative Syndrome Scale (PANSS) Total Score for Schizophrenia

The PANSS scale is used to assess the neuropsychiatric symptoms of schizophrenia. The 30-item PANSS scale provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items),and the general psychopathology subscale (16 items), each item rated on a scale of 1 (absent) to 7 (extreme).

The per-protocol analysis set of patients included those randomized to treatment after IEC/ IRB approval of protocol Amendment INT-4 with both a baseline measurement and at least 1 postrandomization measurement on the primary efficacy variable, a minimum exposure of 36 days to the double-blind treatment regimen, and no major protocol violations.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)

ID	Title	Description
OG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
OG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).

Units	Counts
Participants	OG000389 OG001376

Title

Denominators

Categories

Title	Measurements
	OG000-18.6± 15.45 OG001-17.9± 14.24

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: Difference between groups (RISPERDAL CONSTA minus paliperidone palmitate) for the mean change from baseline to endpoint in PANSS total score (LOCF) was less than or equal to -5 (prespecified non-inferiority margin). Sample size: SD of 20 for the change in PANSS total score, a true difference between treatment groups of 0.1 in favor of RISPERDAL CONSTA, 2-sided significance level of 5%, and 80% power. A sample size reestimation was performed when 60% of the data was available.	ANCOVA	ANCOVA model with factors treatment, country and baseline score. Weighted approach used to account for interim analysis for sample size re-estimation.		No p-value to report.	Mean Difference (Final Values)	0.4	Standard Error of the Mean	1.02	2-Sided	95	-1.62	2.38

Secondary

The Change From Baseline for the CGI-S Score

The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the patient's condition at a given time. A qualified rater administered the CGI-S.

The intent-to-treat (ITT) analysis set of patients included those randomized to treatment after IEC/IRB approval of protocol Amendment INT-4 who received at least 1 injection of double-blind study drug and had at least 1 efficacy measurement during the double-blind treatment period.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)]

ID	Title	Description
OG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
OG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).

Units	Counts
Participants

Secondary

The Change From Baseline in the PSP Score

The PSP scale is used to assess the degree of dysfunction a patient exhibits over a 7-day period within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numeric score. A score between 71 and 100 indicates a mild degree of difficulty; a score between 31 and 70 indicates a moderate degree of dysfunction, and a patient with a score of 30 or less has functioning so poor he or she requires intensive supervision.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)

ID	Title	Description
OG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
OG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Volvulus of small bowel	Gastrointestinal disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Death	General disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Malaria	Infections and infestations	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Urinary tract infection	Infections and infestations	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Syncope	Nervous system disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Agitation	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0002 affected606 at risk EG0012 affected608 at risk
Alcohol abuse	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Anxiety	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0002 affected606 at risk EG0010 affected608 at risk
Completed suicide	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Delirium	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Delusion	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Depressive symptom	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Hallucination	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Hallucination, auditory	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Hallucination, visual	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Paranoia	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0003 affected606 at risk EG0011 affected608 at risk
Psychotic disorder	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG00013 affected606 at risk EG0017 affected608 at risk
Schizophrenia	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG00015 affected606 at risk EG00113 affected608 at risk
Schizophrenia, paranoid type	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Suicidal ideation	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0003 affected606 at risk EG0010 affected608 at risk
Suicide attempt	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk
Tension	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG0001 affected606 at risk EG0010 affected608 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MEDDRA 12.0	Non-systematic Assessment	EG0000 affected606 at risk EG0011 affected608 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Birmingham	Alabama		United States

ID	Term
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D007555	Isoxazoles
D001393	Azoles

ID	Title	Description
BG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
BG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	R092670	Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).			41	606	147	606
EG001	RISPERDAL CONSTA	Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).			29	608	108	608

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site pain	General disorders	MEDDRA 12.0	Non-systematic Assessment	EG00031 affected606 at risk EG0015 affected608 at risk
Headache	Nervous system disorders	MEDDRA 12.0	Non-systematic Assessment	EG00043 affected606 at risk EG00144 affected608 at risk
Somnolence	Nervous system disorders	MEDDRA 12.0	Non-systematic Assessment	EG00034 affected606 at risk EG00124 affected608 at risk
Insomnia	Psychiatric disorders	MEDDRA 12.0	Non-systematic Assessment	EG00057 affected606 at risk EG00141 affected608 at risk

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders