An Open Label Multicentre Study to Determine the Dose Distribution of Paliperidone ER in Patients With Schizophrenia

• Sponsor: Janssen-Cilag Pty Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00473434
• Collaborator: (none)
• Enrollment: 64
• Arm: 1
• Duration (Months): 28

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the dose distribution, effectiveness and safety in patients with schizophrenia who are switched from an oral atypical antipsychotic to Paliperidone ER. In this study patients and physicians know the name and the dose of the study drug. Newly diagnosed patients will also be included in the study. In general, the recommended Paliperidone ER dose will be 6 mg once daily, however some patients may require a higher or lower initial dose in the recommended range of 3 to 12 mg once daily. The dose can be adjusted any point during the study, to a maximum dose of 12mg/day. Flexible dosing was chosen to best mimic actual clinical practice.The safety assessments to be conducted throughout this study including the regular monitoring and recording of all Adverse Events and Serious Adverse Events.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Paliperidone	Phase 3

Detailed Description

This trial is a non-randomised (both patient and physician know the study drug), single arm, open label multicentre study which is aimed to evaluate the dose distribution, efficacy and safety in patients with schizophrenia who are switched from an oral atypical antipsychotic to Paliperidone ER. Newly diagnosed patients will also be included in the study. In general, the recommended Paliperidone ER dose will be 6 mg once daily, however some patients may require a higher or lower initial dose in the recommended range of 3 to 12 mg once daily. The dose can be adjusted any point during the study, to a maximum dose of 12mg/day. Flexible dosing was chosen to best mimic actual clinical practice.The study duration will be split into two phases. Phase A will be 12 weeks and Phase B which will be an optional follow up phase will be 40 weeks. Assessment of efficacy and safety will be performed in Phase A at baseline, 2, 4, 6, 9 and 12 weeks and in Phase B at 20, 28, 36, 44 and 52 weeks. At the first visit, a full psychiatric history, demographic data and physical examination will be undertaken. Throughout the study, the following procedures, documentations and evaluations will be performed: descriptions of concomitant medications; hospitalisations for psychiatric reasons; clinical deterioration; Clinical Global Impression - Severity (CGI-S) and Global Assessment of Functioning (GAF) assessments; Community Treatment Order (CTO) status; weight; adherence and adverse event reporting. Physical examinations will be performed periodically. Paliperidone ER OROS will be supplied in 3 mg, 6 mg, and 9 mg tablets for oral administration. In general, the recommended Paliperidone ER dose will be 6 mg once daily, however some patients may require a higher or lower initial dose in the recommended range of 3 to 12 mg once daily. The dose can be adjusted any point during the study, to a maximum dose of 12mg/day. The study duration will be split into two phases. Phase A will be 12 weeks and Phase B which will be an optional follow up phase

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Multicentre Study to Determine the Dose Distribution of Paliperidone ER in Patients With Schizophrenia
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Paliperidone3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Drug: Paliperidone; 3mg or 6mg or 9mg or 12mg once daily for 52 weeks

Outcome Measures

Primary Outcome Measures

1. The Mean Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 1 to Day 84 [Day 1 to Day 84]

2. The Median Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 1 to Day 84 [Day 1 to Day 84]

3. The Mean Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 57 to Day 84 [Day 57 to Day 84]

4. The Median Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 57 to Day 84 [Day 57 to Day 84]

5. The Mean Overall Average Daily-prescribed Dose of Paliperidone Extended Release (ER) From Week 0 to Week 12 [Week 0 to Week 12]

6. The Median Overall Average Daily-prescribed Dose of Paliperidone Extended Release (ER) From Week 0 to Week 12 [Week 0 to Week 12]

Secondary Outcome Measures

1. The Clinical Global Impression of Severity (CGI-S) Throughout the Study [52 weeks]

   The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill patients".

2. The Global Assessment of Functioning (GAF) Throughout the Study [52 Weeks]

   The GAF is a 100-point tool rating overall psychological, social and occupational functioning of adults. The higher score range (91-100) refers to a superior functioning in a wide range of activities, and absence of symptoms. The lower score range (1-10) refers to persistent danger of severely hurting self or others; or persistent inability to maintain minimum personal hygiene; or serious suicidal act with clear expectation of death.

3. The Percentage of Participants Presenting Clinical Deterioration Throughout the Study [52 Weeks]

   This Outcome Measure is intended to document only the hospitalizations associated with clinical deterioration, ie, when the patient needs to be hospitalized due to exacerbation of psychotic symptoms.

4. The Number of Hospitalizations Throughout the Study [52 Weeks]

   This outcome measure is intended to document all hospitalizations that occurred throughout the study.

5. The Length of Hospitalizations Throughout the Study [52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must satisfy the following criteria to be eligible for this study: patients with diagnoses of schizophrenia according to the DSM-IV criteria including newly diagnosed patients

• Out-patients or in-patients with expected discharge within 8 weeks

• Patients or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from participating in the study: patients who are resistant to antipsychotic treatment

• Patients who have been on clozapine or long-acting injectable antipsychotic medication during the last 3 months

• Patients with CGl-S scores > 6 or who who have been hospitalized for longer than 8 continuous weeks during the past 6 months

• Pregnant or breast-feeding females

• Patients with a history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Janssen-Cilag Pty Ltd

Investigators

• Study Director: Janssen-Cilag Pty Ltd Clinical Trial, Janssen-Cilag Pty Ltd

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• An open label multicentre study to determine the dose distribution of Paliperidone ER OROS® in patients with schizophrenia

Publications

None provided.

• Responsible Party: Janssen-Cilag Pty Ltd
• ClinicalTrials.gov Identifier: NCT00473434
• Other Study ID Numbers: CR013213; R076477SCH3021
• First Posted: May 15, 2007
• Last Update Posted: Dec 5, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by Janssen-Cilag Pty Ltd: Schizophrenia; Drug Therapy; Treatment Outcome
• Additional relevant MeSH terms: Schizophrenia; Paliperidone Palmitate

Study Results

Participant Flow

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Period Title: Overall Study
STARTED	64
COMPLETED	32
NOT COMPLETED	32

Baseline Characteristics

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Overall Participants	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.0 (10.4)
Sex: Female, Male (Count of Participants)
Female	36 56.3%
Male	28 43.8%

Outcome Measures

1. Primary Outcome

Title	The Mean Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 1 to Day 84
Time Frame	Day 1 to Day 84

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63
Mean (Standard Deviation) [mg]	6.9 (2.3)

2. Primary Outcome

Title	The Median Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 1 to Day 84
Time Frame	Day 1 to Day 84

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63
Median (95% Confidence Interval) [mg]	6

3. Primary Outcome

Title	The Mean Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 57 to Day 84
Time Frame	Day 57 to Day 84

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population, excluding participants no longer participating in the study at Day 57

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	53
Mean (Standard Deviation) [mg]	7.5 (2.4)

4. Primary Outcome

Title	The Median Modal Prescribed Daily Dose of Paliperidone Extended Release (ER) From Day 57 to Day 84
Time Frame	Day 57 to Day 84

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population, excluding participants no longer participating in the study at Day 57

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	53
Median (95% Confidence Interval) [mg]	6

5. Primary Outcome

Title	The Mean Overall Average Daily-prescribed Dose of Paliperidone Extended Release (ER) From Week 0 to Week 12
Time Frame	Week 0 to Week 12

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63
Mean (Standard Deviation) [mg]	6.8 (1.8)

6. Primary Outcome

Title	The Median Overall Average Daily-prescribed Dose of Paliperidone Extended Release (ER) From Week 0 to Week 12
Time Frame	Week 0 to Week 12

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63
Median (95% Confidence Interval) [mg]	6

7. Secondary Outcome

Title	The Clinical Global Impression of Severity (CGI-S) Throughout the Study
Description	The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill patients".
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All participants with evaluable data at each measurement time point

Arm/Group Title	Baseline	Week 2	Week 4	Week 6	Week 9	Week 12	Week 20	Week 28	Week 36	Week 44	Week 52
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63	38	36	34	28	31	27	14	14	17	16
Mean (Standard Deviation) [scores on a scale]	3.7 (1.2)	3.3 (1.1)	3.2 (1.0)	3.1 (1.1)	2.8 (1.0)	2.8 (1.0)	2.9 (1.1)	2.7 (1.1)	2.7 (0.8)	2.9 (1.2)	2.7 (0.8)

8. Secondary Outcome

Title	The Global Assessment of Functioning (GAF) Throughout the Study
Description	The GAF is a 100-point tool rating overall psychological, social and occupational functioning of adults. The higher score range (91-100) refers to a superior functioning in a wide range of activities, and absence of symptoms. The lower score range (1-10) refers to persistent danger of severely hurting self or others; or persistent inability to maintain minimum personal hygiene; or serious suicidal act with clear expectation of death.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

All participants with evaluable data at each measurement time point

Arm/Group Title	Baseline	Week 2	Week 4	Week 6	Week 9	Week 12	Week 20	Week 28	Week 36	Week 44	Week 52
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63	38	36	34	28	31	27	14	14	17	16
Mean (Standard Deviation) [scores on a scale]	54.6 (14.7)	58.9 (15.0)	63.9 (15.3)	63.9 (15.6)	66.3 (13.8)	65.4 (14.6)	65.1 (14.7)	71.1 (13.3)	71.6 (14.9)	69.0 (17.2)	63.3 (15.7)

9. Secondary Outcome

Title	The Percentage of Participants Presenting Clinical Deterioration Throughout the Study
Description	This Outcome Measure is intended to document only the hospitalizations associated with clinical deterioration, ie, when the patient needs to be hospitalized due to exacerbation of psychotic symptoms.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

All participants with evaluable data at each measurement time point

Arm/Group Title	Baseline	Week 2	Week 4	Week 6	Week 9	Week 12	Week 20	Week 28	Week 36	Week 44	Week 52
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63	38	36	34	28	31	27	14	14	17	16
Hospitalized	0 (14.7) 0%	5.3 (15.0) NaN	13.5 (15.3) NaN	5.9 (15.6) NaN	7.1 (13.8) NaN	3.2 (14.6) NaN	3.7 (14.7) NaN	0 (13.3) NaN	0 (14.9) NaN	0 (17.2) NaN	12.5 (15.7) NaN
Care Increase	0 0%	0 NaN	5.4 NaN	2.9 NaN	3.6 NaN	3.2 NaN	7.4 NaN	0 NaN	0 NaN	5.9 NaN	12.5 NaN
Suicidal	4.8 7.5%	5.3 NaN	8.1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Violent	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Self Injury	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	3.2 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

10. Secondary Outcome

Title	The Number of Hospitalizations Throughout the Study
Description	This outcome measure is intended to document all hospitalizations that occurred throughout the study.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

All participants with evaluable data at each measurement time point

Arm/Group Title	Baseline	Week 2	Week 4	Week 6	Week 9	Week 12	Week 20	Week 28	Week 36	Week 44	Week 52
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	63	38	36	34	28	31	27	14	14	17	16
Number [events]	15 (14.7)	2 (15.0)	6 (15.3)	2 (15.6)	3 (13.8)	1 (14.6)	1 (14.7)	0 (13.3)	0 (14.9)	1 (17.2)	2 (15.7)

11. Secondary Outcome

Title	The Length of Hospitalizations Throughout the Study
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were hospitalized and had evaluable data at each measurement time point

Arm/Group Title	Baseline	Week 2	Week 4	Week 6	Week 9	Week 12	Week 20	Week 44	Week 52
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
Measure Participants	15	1	3	2	2	1	1	1	2
Mean (Standard Deviation) [days]	12.4 (11.5)	66 (0)	7.3 (6.0)	28.0 (5.7)	179.0 (220.6)	34 (0)	19 (0)	4 (0)	20.5 (10.6)

Adverse Events

Arm/Group Title	Paliperidone Extended Release (ER)
Arm/Group Description	Paliperidone ER 3mg or 6mg or 9mg or 12mg once daily for 52 weeks
All Cause Mortality
	Paliperidone Extended Release (ER)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Paliperidone Extended Release (ER)
	Affected / at Risk (%)	# Events
Total	27/64 (42.2%)
Gastrointestinal disorders
Abdominal pain	1/64 (1.6%)
General disorders
Lethargy	1/64 (1.6%)
Infections and infestations
Encephalitis viral	1/64 (1.6%)
Injury, poisoning and procedural complications
Intentional overdose	1/64 (1.6%)
Overdose	1/64 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma	1/64 (1.6%)
Nervous system disorders
Dystonia	1/64 (1.6%)
Extrapyramidal disorder	1/64 (1.6%)
Psychiatric disorders
Depression	2/64 (3.1%)
Hallucination, auditory	1/64 (1.6%)
Mental disorders	2/64 (3.1%)
Paranoia	2/64 (3.1%)
Psychotic disorder	1/64 (1.6%)
Schizoaffective disorder	2/64 (3.1%)
Schizophrenia	3/64 (4.7%)
Schizophrenia exacerbated	1/64 (1.6%)
Suicidal ideation	5/64 (7.8%)
Other (Not Including Serious) Adverse Events
	Paliperidone Extended Release (ER)
	Affected / at Risk (%)	# Events
Total	51/64 (79.7%)
Cardiac disorders
Dizziness	4/64 (6.3%)
Gastrointestinal disorders
Nausea	6/64 (9.4%)
Nervous system disorders
Headache	7/64 (10.9%)
Sedation	4/64 (6.3%)
Tremor	6/64 (9.4%)
Vision blurred	4/64 (6.3%)
Psychiatric disorders
Akathisia	6/64 (9.4%)
Insomnia	10/64 (15.6%)
Skin and subcutaneous tissue disorders
Rash	4/64 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.