A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia

• Sponsor: Janssen Pharmaceutica (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01606228
• Collaborator: (none)
• Enrollment: 188
• Arm: 1
• Duration (Months): 12

Study Details

Study Description

Brief Summary

The purpose of this study is to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among patients with schizophrenia.

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

Detailed Description

This is a single arm (the same intervention is given to all patients), multicenter study that aimed to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among Filipino patients with schizophrenia who have not taken any antipsychotics in the past, and among newly diagnosed schizophrenia patients who have not taken any antipsychotics for at least one month prior to screening. Antipsychotics are drugs that are helpful in the treatment of psychosis and have a capacity to ameliorate thought disorders. Flexible dosing allows the investigators to adjust the dosage of each patient based on the individual needs.

Study Design

• Study Type: Interventional
• Actual Enrollment: 188 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly-Dosed Paliperidone ER Among Treatment-Naïve and Newly Diagnosed Patients With Schizophrenia
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paliperidone ER	Drug: Paliperidone ER; Type= range, unit= mg/day, number= 3 to 12, form= tablet, route= oral use. Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.

Outcome Measures

Primary Outcome Measures

1. The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90) [Baseline, Day 90]

   The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

Secondary Outcome Measures

1. Positive and Negative Syndrome Scale (PANSS) Scores at Baseline [Baseline]

   The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

2. Positive and Negative Syndrome Scale (PANSS) Scores at Day 90 [Day 90]

   The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

3. Clinical Global Impression-Severity (CGIS) Scores at Baseline [Baseline]

   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. The rating varies from "Normal (not at all ill)" to "Extreme (among the most extremely ill patients)".

4. Clinical Global Impression-Severity (CGIS) Scores at Day 90 [Day 90]

   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. The rating varies from "Normal (not at all ill)" to "Extreme (among the most extremely ill patients)".

5. Personal and Social Performance (PSP) Scores at Baseline [Baseline]

   This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision.

6. Personal and Social Performance (PSP) Scores at Day 90 [Day 90]

   This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision.

7. Patient Satisfaction With Paliperidone Treatment [90 days]

   Patients will be interviewed to assess their satisfaction with the current treatment on a 5-point scale (very good, good, reasonable, moderate or poor).

8. Quality of Sleep at Baseline [Baseline]

   The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well).

9. Quality of Sleep at Day 90 [Day 90]

   The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well).

10. Daytime Drowsiness at Baseline [Baseline]

    The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time).

11. Daytime Drowsiness at Day 90 [Day 90]

    The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients diagnosed with schizophrenia

• Patient with Positive and Negative Syndrome Scale (PANSS) score of 80 to 120 at screening

• Patients who have not taken any antipsychotics in the past, and those were newly diagnosed with schizophrenia who have not taken any antipsychotics for at least one month prior to screening

• Patient healthy on the basis of a physical examination, laboratory examination, and vital signs

• Women must have a negative pregnancy test, and agree to practice an effective method of birth control before entry and throughout the study

Exclusion Criteria:

• Serious unstable medical condition, including known clinically relevant laboratory abnormalities

• Judged to be at high risk for adverse events, violence or self-harm

• Inability to swallow the study medication whole with the aid of water (patients may not chew, divide, dissolve, or crush the study medication)

• Biochemistry results that are out of the laboratory's normal reference range and are deemed to be clinically significant by the investigator

• Patients with a current use or known history (over the past 6 months) of substance dependence

• Positive urine drug examination

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Janssen Pharmaceutica

Investigators

• Study Director: Janssen Pharmaceutica Clinical Trial, Janssen Pharmaceutica

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01606228
• Other Study ID Numbers: CR014452; R076477SCH3033; PAL-PHL-MA3
• First Posted: May 25, 2012
• Last Update Posted: Oct 22, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by , ,: Schizophrenia; Paliperidone ER; Treatment naive patients; Newly diagnosed patients
• Additional relevant MeSH terms: Schizophrenia; Paliperidone Palmitate

Study Results

Participant Flow

Pre-assignment Detail	There were 188 patients enrolled in the study which were included in the safety analysis set. The main analysis set included only 176 subjects due to 12 protocol violations. Of these 176 patients, only 73 were included in the per-protocol analysis set. For the Clinical Global Impression-Severity scores, data was collected for only 60 patients.

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Period Title: Overall Study
STARTED	188
COMPLETED	159
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Overall Participants	176
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.71 (9.743)
Sex: Female, Male (Count of Participants)
Female	70 39.8%
Male	106 60.2%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90)
Description	The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Number [percentage of patients]	97.73

2. Secondary Outcome

Title	Positive and Negative Syndrome Scale (PANSS) Scores at Baseline
Description	The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	108.25 (23.897)

3. Secondary Outcome

Title	Positive and Negative Syndrome Scale (PANSS) Scores at Day 90
Description	The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	48.74 (18.371)

4. Secondary Outcome

Title	Clinical Global Impression-Severity (CGIS) Scores at Baseline
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. The rating varies from "Normal (not at all ill)" to "Extreme (among the most extremely ill patients)".
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population; participants for whom CGIS data was collected.

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	60
Normal	0 0%
Borderline	0 0%
Mild	0 0%
Moderate	11 6.3%
Marked	33 18.8%
Severe	14 8%
Extreme	2 1.1%

5. Secondary Outcome

Title	Clinical Global Impression-Severity (CGIS) Scores at Day 90
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. The rating varies from "Normal (not at all ill)" to "Extreme (among the most extremely ill patients)".
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	60
Normal	0 0%
Borderline	31 17.6%
Mild	20 11.4%
Moderate	8 4.5%
Marked	1 0.6%
Severe	0 0%
Extreme	0 0%

6. Secondary Outcome

Title	Personal and Social Performance (PSP) Scores at Baseline
Description	This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	37.23 (12.675)

7. Secondary Outcome

Title	Personal and Social Performance (PSP) Scores at Day 90
Description	This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	75.66 (10.451)

8. Secondary Outcome

Title	Patient Satisfaction With Paliperidone Treatment
Description	Patients will be interviewed to assess their satisfaction with the current treatment on a 5-point scale (very good, good, reasonable, moderate or poor).
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Very good	33 18.8%
Good	34 19.3%
Moderate	4 2.3%
Poor	1 0.6%
Very poor	1 0.6%

9. Secondary Outcome

Title	Quality of Sleep at Baseline
Description	The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	33.99 (30.091)

10. Secondary Outcome

Title	Quality of Sleep at Day 90
Description	The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well).
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	86.56 (18.684)

11. Secondary Outcome

Title	Daytime Drowsiness at Baseline
Description	The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	21.49 (22.511)

12. Secondary Outcome

Title	Daytime Drowsiness at Day 90
Description	The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time).
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	11.23 (19.061)

Adverse Events

Arm/Group Title	Paliperidone Extended-release (ER)
Arm/Group Description	Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.
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	4/188 (2.1%)
Cardiac disorders
Arrhythmia	1/188 (0.5%)
Ventricular Extrasystoles	1/188 (0.5%)
Nervous system disorders
Akathisia	1/188 (0.5%)
Psychiatric disorders
Schizophrenia paranoid type	1/188 (0.5%)
Schizophrenia	2/188 (1.1%)
Other (Not Including Serious) Adverse Events
	Paliperidone Extended-release (ER)
	Affected / at Risk (%)	# Events
Total	43/188 (22.9%)
Eye disorders
Upward gazing	1/188 (0.5%)
Gastrointestinal disorders
Sialorrhea	3/188 (1.6%)
Constipation	1/188 (0.5%)
Acute Gastroenteritis	1/188 (0.5%)
General disorders
Pyrexia	3/188 (1.6%)
Breast pain	2/188 (1.1%)
Swelling of arm	1/188 (0.5%)
Sore throat	1/188 (0.5%)
Infections and infestations
Otitis media	2/188 (1.1%)
Urinary Tract Infection	2/188 (1.1%)
Fungal infection	2/188 (1.1%)
Upper Respiratory Tract Infection	2/188 (1.1%)
Pharyngitis	1/188 (0.5%)
Scabies	1/188 (0.5%)
Pulmonary Tuberculosis	1/188 (0.5%)
Metabolism and nutrition disorders
Anemia	9/188 (4.8%)
Poor appetite	3/188 (1.6%)
Diabetes	1/188 (0.5%)
Hypokalemia	1/188 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/188 (0.5%)
Sprain	1/188 (0.5%)
Nervous system disorders
Extra-Pyramidal Symptoms	3/188 (1.6%)
Akathisia	3/188 (1.6%)
Restlessness	2/188 (1.1%)
Dizziness/Vertigo	1/188 (0.5%)
Headache	1/188 (0.5%)
Tremors	1/188 (0.5%)
Dystonia	1/188 (0.5%)
Psychiatric disorders
Insomnia	25/188 (13.3%)
Acute psychotic symptoms	3/188 (1.6%)
Disturbed behavior	3/188 (1.6%)
Manic-like behavior	1/188 (0.5%)
Delusions	1/188 (0.5%)
Renal and urinary disorders
Renal Insufficiency	1/188 (0.5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/188 (1.1%)
Colds/nasal congestion	1/188 (0.5%)
Skin and subcutaneous tissue disorders
Pruritus	1/188 (0.5%)
Skin allergy	1/188 (0.5%)
Eczematous lesion	1/188 (0.5%)
Social circumstances
Verbal assault	2/188 (1.1%)
Vascular disorders
Hypertension	3/188 (1.6%)
Orthostatic hypotension	1/188 (0.5%)
External Hemorrhoid	1/188 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.