Paliperidone Extended Release in Schizophrenia Participants With Duration of Illness Less Than 10 Years

Efficacy and Tolerability of Flexible Doses of Paliperidone ER in Symptomatic Subjects With Schizophrenia With Duration of Illness < 10 Years

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01362439

Enrollment

133

Registered

2011-05-30

Start date

2009-01-31

Completion date

2010-03-31

Last updated

2013-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Keywords

Schizophrenia, Paliperidone

Brief summary

The purpose of this study is to evaluate the effectiveness and safety of paliperidone extended release (ER) in symptomatic participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) who were receiving treatment with any oral (having to do with the mouth) antipsychotic medication and who needed to be switched to paliperidone ER from the current oral antipsychotic therapy due to insufficient efficacy or due to side effects.

Detailed description

This is an open-label (all people know the identity of the intervention), multi-centric (conducted in more than one center) and non-comparative study of paliperidone ER in participants with schizophrenia who have a previous history of bad adherence to the antipsychotic treatment because of insufficient efficacy and side-effects. All the eligible participants will receive a dose of paliperidone ER in range of 3 to 12 milligram (mg) orally (taken by mouth; to be swallowed) once daily for 13 weeks. Efficacy and safety will primarily be evaluated by Positive and Negative Syndromes Scale (PANSS) and Extrapyramidal Symptom Rating Scale (ESRS), respectively. Participants' safety will be monitored throughout the study.

Interventions

DRUGPaliperidone ER

Participants will be administered paliperidone extended release (ER) tablets orally (taken by mouth; to be swallowed) once daily in the dose range of 3 to 12 milligram (mg) for 13 weeks. Dose will be increased or decreased as per Investigator's discretion.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Inclusion criteria

* Participants meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) * Positive and Negative Syndrome Scale (PANSS) total score at Baseline of greater than equal to 70 and less than equal to 100 * Participants who need to be switched from the current oral antipsychotic therapy because of lack of efficacy or side effects * Participants followed as outpatients * Female participants must be postmenopausal for at least 1 year, surgically sterile or, if sexually active, be practicing an effective method of birth control and female participants of childbearing potential must also have a negative urine pregnancy test at Baseline

Exclusion criteria

* Acute psychotic relapse that requires hospitalization and first antipsychotic treatment ever * Participants who had received clozapine during the previous 3 months * History or current symptoms of tardive dyskinesia (twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body) and neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness) * Pregnant or breast-feeding female * Participated in an investigational drug trial in the previous 30 days

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 13	Baseline and Week 13	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) 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 and ranges from 30 to 210, higher scores indicate worsening.

Secondary

Measure	Time frame	Description
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score at Week 13	Baseline and Week 13	The PANSS Negative Subscale assesses seven negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).
Change in Positive and Negative Syndrome Scale (PANSS) General Psychopathology Subscale Score at Week 13	Baseline and Week 13	The PANSS General Psychopathology Subscale Score assesses 16 general psychopathology symptoms. The symptoms are rated on a 7-point scale, with a range of 16 (absent) to 112 (extreme psychopathology).
Percentage of Participants With Greater Than or Equal to 30 Percent Treatment Response in Total Positive and Negative Syndrome Scale (PANSS) Score	Baseline and Week 13	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) 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 and ranges from 30 to 210, higher scores indicate worsening.
Change From Baseline in Subjective Well-being Under Neuroleptic (SWN 20) Scale at Week 13	Baseline and Week 13	The SWN 20 scale is a 20 item scale that was originally designed to explore the subjective experience of psychotic participants. The SWN scale contains five sub-scales consisting of four items each: mental functioning (MF), self control (SC), emotional regulation (ER), and social integration (SI), physical functioning (PF). The total score ranges from a minimum of 20 (poor subjective experience) to a maximum of 120 (excellent subjective experience). SWN scores appear to correlate with measure of objective psychopathology, quality of life and other self-ratings of mood.
Change From Baseline in Drug Attitude Inventory (DAI 30) Scale at Week 13	Baseline and Week 13	The DAI is a 30-item self-rating inventory that focuses on subjective effects of neuroleptic medications in participants with schizophrenia. There are 15 items that are scored as true and 15 scored as false if the person is fully compliant (positive subjective response). Positive answers score as +1, negative answers score as - 1. Questionnaire allows identifying participants at high risk of low compliance. The total score may vary from -30 to +30 with a high total final score is a positive subjective response (compliant) and a low total score is a negative subjective response (non-compliant).
Change in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score at Week 13	Baseline and Week 13	The PANSS Positive Subscale assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).
Change From Baseline in Personal and Social Performance Scale (PSP) at Week 13	Baseline and Week 13	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).
Quality of Sleep Score	Baseline and Week 13	This self-administered scale rates quality of sleep and daytime drowsiness. Participants indicate on an 11-point scale how well they have slept in the previous 7 days, from 0 (very badly) to 10 (very well); and how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 10 (all the time). On the sleep evaluation scale, score 0 corresponds to very badly and score 10 to very well.
Daytime Drowsiness Evaluation Scale	Baseline and Week 13	This self-administered scale rates quality of sleep and daytime drowsiness. Participants will indicate on an 11-point scale how well they have slept in the previous 7 days, from 0 (very badly) to 10 (very well); and how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 10 (all the time).On the daytime drowsiness scale, score 0 corresponds to not at all and score 10 to all the time.
Extrapyramidal Symptoms Scale (ESRS) Subscale Scores and Total Scores	Baseline and Week 13	Extra pyramidal symptoms attributed to antipsychotic assessed by ESRS scale. Included 4 subscales; Parkinsonism (Park),dystonia(Dyst),dyskinesia(Dysk),akathisia(Akat),12 items on 4-point scale; (0=absent-3=severe); Park (8 items); Dyst (2 items); Dysk (7 items) all 3 rated on 7-point scale (0=none/normal-6=worst). Additionally, subtotals were calculated; hyperkinesia (item 5, 6 of Park); hypokinesia (item 1-4, 7 of Park); bucco-linguo-masticatory (item 1-3 of Dysk), choreoathetoid movement (item 5, 6 of Dysk). Total score: sum of Park, Dyst & Dysk subscale, ranged from 0 (normal)-102 (severe).
Clinical Global Impression-Severity Scale (CGI-S)	Baseline and Week 13	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. Higher scores indicate worsening.

Participant flow

Participants by arm

Arm	Count
Paliperidone ER Participants were administered paliperidone extended release (ER) tablets orally (taken by mouth; to be swallowed) once daily in the dose range of 3 to 12 milligram (mg) for 13 weeks. Dose was increased or decreased as per Investigator's discretion.	132
Total	132

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Lack of Efficacy	3
Overall Study	Lost to Follow-up	2
Overall Study	Participant who withdrew consent	8
Overall Study	Study medication non-compliant	1

Baseline characteristics

Characteristic	Paliperidone ER
Age Continuous	35.3 years STANDARD_DEVIATION 6.76
Sex: Female, Male Female	41 Participants
Sex: Female, Male Male	91 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	21 / 132
serious Total, serious adverse events	1 / 132

Outcome results

Primary

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 13

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) 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 and ranges from 30 to 210, higher scores indicate worsening.