Trial Outcomes & Findings for An Efficacy, Safety And Tolerability Study of Flexibly Dosed Paliperidone Extended-Release (ER) in Participants With Schizophrenia (NCT NCT00757705)

Last Updated: 2014-02-06

Results Overview

The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides 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 item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

299 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2014-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	Paliperidone Extended Release (ER) Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Overall Study STARTED	299
Overall Study COMPLETED	178
Overall Study NOT COMPLETED	121

Reasons for withdrawal

Reasons for withdrawal
Measure	Paliperidone Extended Release (ER) Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Overall Study Adverse Event	19
Overall Study Lost to Follow-up	16
Overall Study Withdrawal by Subject	25
Overall Study Insufficient Response	26
Overall Study Ineligible to continue	8
Overall Study Non-compliant	9
Overall Study Other	18

Baseline Characteristics

An Efficacy, Safety And Tolerability Study of Flexibly Dosed Paliperidone Extended-Release (ER) in Participants With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paliperidone Extended Release (ER) n=299 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Age, Continuous	40.1 years STANDARD_DEVIATION 11.85 • n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants
Sex: Female, Male Male	137 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using last observation carried forward (LOCF). Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=297 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 Baseline (n=297)	72.4 Units on a scale Standard Deviation 21.1
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 Change at Week 24 (n=281)	-6.9 Units on a scale Standard Deviation 17.3

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.

The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Marder PANSS subscales include positive symptoms subscale consisting of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consisting of 7 items with total score range of 7-49; and uncontrolled hostility/excitement (UH/E) subscale and anxiety/depression subscale, each consisting of 4 items with total score range of 4-28. Higher score indicates greater severity.

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=297 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Negative symptoms: Baseline (n=297)	17.0 Units on a scale Standard Deviation 7.0
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Negative symptoms:Change at Week 24 (n=281)	-1.7 Units on a scale Standard Deviation 4.4
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Positive symptoms:Change at Week 24 (n=281)	-2.2 Units on a scale Standard Deviation 5.6
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Disorganized thoughts: Baseline (n=297)	16.7 Units on a scale Standard Deviation 6.6
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Disorganized thoughts: Change at Week 24 (n=281)	-1.4 Units on a scale Standard Deviation 4.4
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 UH/E: Baseline (n=297)	7.5 Units on a scale Standard Deviation 3.3
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 UH/E: Change at Week 24 (n=281)	-0.5 Units on a scale Standard Deviation 3.9
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Anxiety/depression: Baseline (n=297)	9.7 Units on a scale Standard Deviation 3.8
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Anxiety/depression:Change at Week 24(n=281)	-1.1 Units on a scale Standard Deviation 3.5
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 Positive symptoms: Baseline (n=297)	21.6 Units on a scale Standard Deviation 7.2

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Here 'N' (Number of Participants Analyzed) signifies participants evaluable for this measure.

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=281 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Percentage of Participants With at Least 20 Percent Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score	31.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty).

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=297 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24 Baseline (n=297)	54.5 Units on a scale Standard Deviation 13.8
Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24 Change at Week 24 (n=269)	3.4 Units on a scale Standard Deviation 12.7

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population: all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here 'N' (Number of Participants Analyzed) signifies number of participants who were evaluable for this measure. 'n' signifies those participants who were evaluable at specified time point.

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.

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=273 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24 Baseline (n=273)	48.9 Units on a scale Standard Deviation 14.7
Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24 Change at Week 24 (n=246)	5.8 Units on a scale Standard Deviation 15.2

SECONDARY outcome

Timeframe: Baseline, Week 24

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 participant. 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 participants".

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=297 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24 Baseline (n=297)	4.3 Units on a scale Standard Deviation 1.1
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24 Change at Week 24 (n=279)	-0.5 Units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Week 24

The SF-36 is a health status survey with 36 questions measuring 8 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are subsequently aggregated into 2 summary scales, Physical Component Summary (PCS) and Mental Component Summary (MCS). Each item is scored into on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=295 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 PCS: Baseline (n=293)	61.3 Units on a scale Standard Deviation 19.8
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 PCS: Change at Week 24 (n=225)	0.6 Units on a scale Standard Deviation 16.1
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 MCS: Baseline (n=295)	53.1 Units on a scale Standard Deviation 21.5
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 MCS: Change at Week 24 (n=228)	2.0 Units on a scale Standard Deviation 18.4

SECONDARY outcome

Timeframe: Week 24

Participants assessed their satisfaction with paliperidone ER on a 5-point scale (very good, good, moderate, poor or very poor).

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=237 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Number of Participants With Satisfaction With the Study Treatment Very good	11 Participants
Number of Participants With Satisfaction With the Study Treatment Good	83 Participants
Number of Participants With Satisfaction With the Study Treatment Moderate	83 Participants
Number of Participants With Satisfaction With the Study Treatment Poor	49 Participants
Number of Participants With Satisfaction With the Study Treatment Very poor	11 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.

The Sleep Quality and Daytime Drowsiness evaluation scale is a self-administered scale that rates quality of sleep and daytime drowsiness. Participants indicated on a 5 point scale how well they have slept in the previous 7 days, score ranging from 1 (very badly) to 5 (very well) and how often they have felt drowsy within the previous 7 days, score ranging from 1 (not at all) to 5 (all the time).

Outcome measures

Outcome measures
Measure	Paliperidone Extended Release (ER) n=297 Participants Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 Quality of sleep: Baseline (n=297)	3.2 Units on a scale Standard Deviation 1.0
Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 Quality of sleep:Change at Week 24 (n=278)	0.1 Units on a scale Standard Deviation 1.1
Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 Daytime drowsiness: Baseline (n=297)	2.6 Units on a scale Standard Deviation 1.0
Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 Daytime drowsiness:Change at Week 24 (n=278)	-0.3 Units on a scale Standard Deviation 1.2

Adverse Events

Paliperidone Extended Release (ER)

Serious events: 11 serious events

Other events: 180 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Paliperidone Extended Release (ER) n=299 participants at risk Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Infections and infestations Cellulitis	0.33% 1/299 • Baseline up to Week 24
Injury, poisoning and procedural complications Fall	0.33% 1/299 • Baseline up to Week 24
Investigations Blood Electrolytes Abnormal	0.33% 1/299 • Baseline up to Week 24
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic Neoplasm Malignant	0.33% 1/299 • Baseline up to Week 24
Nervous system disorders Haemorrhage Intracranial	0.33% 1/299 • Baseline up to Week 24
Pregnancy, puerperium and perinatal conditions Pregnancy	0.33% 1/299 • Baseline up to Week 24
Psychiatric disorders Delirium	0.33% 1/299 • Baseline up to Week 24
Psychiatric disorders Hallucination, Auditory	0.33% 1/299 • Baseline up to Week 24
Psychiatric disorders Insomnia	0.33% 1/299 • Baseline up to Week 24
Psychiatric disorders Psychotic Disorder	0.33% 1/299 • Baseline up to Week 24
Psychiatric disorders Schizophrenia	0.33% 1/299 • Baseline up to Week 24

Other adverse events

Other adverse events
Measure	Paliperidone Extended Release (ER) n=299 participants at risk Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug.
Cardiac disorders Palpitations	2.0% 6/299 • Baseline up to Week 24
Gastrointestinal disorders Constipation	9.7% 29/299 • Baseline up to Week 24
Immune system disorders Hypersensitivity	2.0% 6/299 • Baseline up to Week 24
Infections and infestations Cellulitis	2.0% 6/299 • Baseline up to Week 24
Infections and infestations Upper Respiratory Tract Infection	10.0% 30/299 • Baseline up to Week 24
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 6/299 • Baseline up to Week 24
Musculoskeletal and connective tissue disorders Muscle Rigidity	3.7% 11/299 • Baseline up to Week 24
Nervous system disorders Akathisia	6.0% 18/299 • Baseline up to Week 24
Nervous system disorders Bradykinesia	2.0% 6/299 • Baseline up to Week 24
Nervous system disorders Dizziness	3.3% 10/299 • Baseline up to Week 24
Nervous system disorders Extrapyramidal Disorder	13.7% 41/299 • Baseline up to Week 24
Nervous system disorders Headache	4.7% 14/299 • Baseline up to Week 24
Nervous system disorders Parkinsonism	2.7% 8/299 • Baseline up to Week 24
Nervous system disorders Sedation	3.3% 10/299 • Baseline up to Week 24
Nervous system disorders Somnolence	2.0% 6/299 • Baseline up to Week 24
Nervous system disorders Tremor	5.0% 15/299 • Baseline up to Week 24
Psychiatric disorders Agitation	2.3% 7/299 • Baseline up to Week 24
Psychiatric disorders Anxiety	11.7% 35/299 • Baseline up to Week 24
Psychiatric disorders Depression	9.0% 27/299 • Baseline up to Week 24
Psychiatric disorders Hallucination, Auditory	3.3% 10/299 • Baseline up to Week 24
Psychiatric disorders Insomnia	20.7% 62/299 • Baseline up to Week 24
Psychiatric disorders Panic Disorder	2.3% 7/299 • Baseline up to Week 24
Psychiatric disorders Sleep Disorder	2.7% 8/299 • Baseline up to Week 24
Respiratory, thoracic and mediastinal disorders Cough	2.0% 6/299 • Baseline up to Week 24
Skin and subcutaneous tissue disorders Dermatitis	2.7% 8/299 • Baseline up to Week 24
Skin and subcutaneous tissue disorders Dermatitis Contact	2.0% 6/299 • Baseline up to Week 24
Skin and subcutaneous tissue disorders Pruritus	2.7% 8/299 • Baseline up to Week 24

Additional Information

Medical Director

Janssen Research & Development

Phone: 886 2 23762155

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60