Tolerability, Safety and Efficacy of Flexibly Dosed Paliperidone ER in Patients With Schizophrenia

An Open-label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly Dosed Paliperidone ER in Subjects With Schizophrenia

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01724359

Acronym

PERFLEX

Enrollment

Registered

2012-11-09

Start date

2008-02-29

Completion date

2009-11-30

Last updated

2013-03-15

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

Conditions

Schizophrenia

Keywords

Schizophrenia, Paliperidone extended-release (ER), Antipsychotic agents

Brief summary

The purpose of this study is to evaluate efficacy, safety and tolerability of flexible, once-daily doses of paliperidone extended-release (ER) in patients with schizophrenia from Argentina and Colombia that previously failed treatment with other antipsychotic agents.

Detailed description

This is a single arm (one group of patients), open-label (all people know the identity of the intervention) multicenter 6-month study. Throughout the study flexible dosing of paliperidone ER in a range of 3 to 12 mg/day may be used. Flexible dosing will allow investigators to adjust the dosage of each patient based on the individual needs. Patients will receive 3, 6, 9 or 12 mg of paliperidone ER once daily for 6 months. The tablets will be taken orally. Adjustment of the dosage will be done at the investigator's discretion, based on the individual patient's clinical response and tolerability to the study drug.

Interventions

DRUGPaliperidone ER

The recommended Paliperidone extended-release (ER) dose will be 6 mg/day. Some patients may benefit from higher or lower doses, in the range of 3 to 12 mg/day. Paliperidone ER will be administered orally once daily. Adjustment of the dosage will be done at the investigator's discretion.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patient meets the criteria for schizophrenia * Patient is previously non-acute and has been given an adequate dose of an appropriate oral antipsychotic for an adequate period of time prior to enrollment, but previous treatment is considered unsuccessful due to one or more of the following reasons: lack of efficacy, lack of tolerability or safety, lack of compliance and/or other reasons to switch to another antipsychotic medication * Patient is healthy on the basis of a physical examination and vital signs at screening * Women must be postmenopausal for at least 1 year, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study

Exclusion criteria

* Patients on clozapine, any conventional depot neuroleptic or risperidone long-acting injections during the last 3 months * Patients with serious unstable medical condition, including known clinically relevant laboratory abnormalities * Patients with history or current symptoms of tardive dyskinesia and neuroleptic malignant syndrome * Patients judged to be at high risk for adverse events, violence, or self-harm * Patients with known hypersensitivity to paliperidone ER or to risperidone * Patients with a current use or known history (over the past 6 months) of substance dependence

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score	Baseline, Week 26	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia. 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 Total Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score	Baseline, Week 26	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 From Baseline in Total Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score	Baseline, Week 26	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).
Clinical Global Impression-Severity (CGIS)	Baseline, Week 26	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. Higher scores indicate worsening.
Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score	Baseline, Week 26	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).
Health Status as Measured by Self-rated Health Status Survey SF-36	Baseline, Week 26	The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts.
Sleep Evaluation Scale	Baseline, Week 26	This self-administered scale rates the quality of sleep. Patients 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).
Daytime Drowsiness Evaluation Scale	Baseline, Week 26	This self-administered scale rates the daytime drowsiness. Patients will indicate on an 11-point scale how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 10 (all the time).
Personal and Social Performance (PSP) Scale	Baseline, Week 26	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.

Countries

Argentina, Colombia

Participant flow

Pre-assignment details

Patients who received paliperidone extended-release (ER) at least once and provide at least 1 post baseline efficacy measurement will be included in the intent-to-treat (ITT) analysis set for efficacy. Patients who received paliperidone ER at least once and provide any post-baseline information will be included in the ITT analysis set for safety.

Participants by arm

Arm	Count
Paliperidone Extended-release (ER) The recommended Paliperidone ER dose is 6 mg/day. Some patients may benefit from higher or lower doses, in the range of 3 to 12 mg/day. Paliperidone ER will be administered orally once daily.	95
Total	95

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	10
Overall Study	Death	1
Overall Study	Other	20

Baseline characteristics

Characteristic	Paliperidone Extended-release (ER)
Age Continuous	35.86 years STANDARD_DEVIATION 12.28
Region of Enrollment Argentina	37 participants
Region of Enrollment Colombia	58 participants
Sex: Female, Male Female	41 Participants
Sex: Female, Male Male	54 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	39 / 95
serious Total, serious adverse events	7 / 95

Outcome results

Primary

Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia. 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.

Time frame: Baseline, Week 26