A Study of Flexibly Dosed Paliperidone Extended Release Tablets in Participants With Schizophrenia

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01541371

Enrollment

405

Registered

2012-02-29

Start date

2008-07-31

Completion date

2009-09-30

Last updated

2013-08-07

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 tablets

Brief summary

The purpose of this study is to evaluate the effectiveness of paliperidone extended-release (ER; designed to slowly release a drug in the body over an extended period of time) tablets in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions \[a false belief held in the face of strong differing evidence, especially as a symptom of psychiatric disorder\] and hallucinations \[imagining things\], and withdrawal into the self) who were not satisfied with other prior antipsychotics (agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect; olanzapine, quetiapine and risperidone) they had been taking. The safety and tolerability of paliperidone ER tablets will also be assessed.

Detailed description

This is an open label (all people know the identity of the intervention), prospective (study following participants forward in time), non-randomized (the study drug is not assigned by chance, participants may choose which group they want to be in, or they may be assigned to the groups by the researchers), single-arm (getting one dose of medicine) and multi-center (when more than one hospital or medical school team work on a medical research study) study designed to determine the efficacy, tolerability and safety of flexible dosage of paliperidone ER tablets in treatment of participants with schizophrenia not satisfied with other prior antipsychotics. The duration of the study will be 12 weeks. All participants will be given paliperidone ER 3 milligram (mg) or 6 mg or 9 mg or 12 mg oral (by mouth) tablets depending on Investigator's discretion once daily for 12 weeks; initial dose for paliperidone ER will be 6 mg/day. The primary objective will be to evaluate the efficacy of treatment with paliperidone ER using Positive and Negative Symptom Scale (PANSS) total scores. Participants safety and tolerability will be monitored throughout the study.

Interventions

DRUGPaliperidone ER

Paliperidone Extended Release (ER) 3 milligram (mg) or 6 mg or 9 mg or 12 mg oral (by mouth) tablets depending on Investigator's discretion once daily for 12 weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Participants meeting Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis criteria of schizophrenia * Participant receiving full course of treatment (6-8 weeks) at correct dose (dose range recommended by the instruction) of Risperdal, Zyprexa or Seroquel before enrollment, was poorly controlled and had to change medication because of unsatisfying efficacy, tolerability or safety issues, or other reason * Participant in the non-acute phase during screening received treatment with any of above three antipsychotics within 4 weeks before enrollment and state of illness was relatively stable * 7\. Female participants 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. Effective methods of birth control include prescription hormonal contraceptives, contraceptive injections, intrauterine devices, double barrier method, contraceptive patch and male partner sterilization. Female participants must also have a negative urine pregnancy test at screening * Participant willing to and who could complete questionnaire by himself

Exclusion criteria

* Participant receiving treatment with clozapine or risperidone microspheres for injection (Hengde) within 3 months before screening * Participant having history of seizure except febrile convulsion (seizures that occur during a febrile episode \[fever\]) * Participant having refractory schizophrenia (previous treatment with unsatisfied efficacy of 2 or more than 2 kinds of antipsychotics with different chemical structure after adequate dose and duration) * Participant receiving electric shock treatment within 1 month before screening * Participant having serious, unstable physical diseases

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12	Baseline and Week 12	PANSS is a medical scale that assesses various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions \[a false belief held in the face of strong differing evidence, especially as a symptom of psychiatric disorder\] and hallucinations \[imagining things\], and withdrawal into the self). The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).

Secondary

Measure	Time frame	Description
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 12	Baseline and Week 12	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). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher change score indicates greater severity.
Percentage of Participants With Response to Positive and Negative Syndrome Scale (PANSS) Total Score	Week 12	PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill). Percentage of participants with at least 20 percent improvement of PANSS total score was measured.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12	Baseline and Week 12	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 change scores indicate worsening.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores at Week 12	Baseline and Week 12	PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill). Positive syndrome subscale ranges from 7 to 49, higher change scores indicate worsening. Negative syndrome subscale ranges from 7 to 49, higher change scores indicate worsening. General Psychopathology subscale ranges from 16 to112, higher change scores indicate worsening.
Number of Participants With Satisfaction With the Study Treatment	Baseline and Week 12	Participants assessed their satisfaction with paliperidone ER on a 5-point scale: 1 (very good), 2 (good), 3 (moderate), 4 (poor) and 5 (very poor).
Change From Baseline in Sleep and Daytime Drowsiness Evaluation Score at Week 12	Baseline and Week 12	The self-administered sleep VAS scale (0-100 milimeter \[mm\]) rates quality of sleep (QoS) and daytime drowsiness (DD). Participants indicate mark on the scale to represent how well they have slept in the previous 7 days, score ranges from 0 mm (very badly) to 100 mm (very well); and how often they have felt drowsy within the previous 7 days, from 0 mm (not at all) to 100 mm (all the time).
Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 12	Baseline and Week 12	PSP assesses the degree of a participant'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 (1, absent to 6, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Participants 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.

Participant flow

Recruitment details

Participants were recruited from 19 study centers between 30 July 2008 and 23 September 2009.

Pre-assignment details

405 participants were enrolled, out of which 403 participants were recruited in Safety Analysis Set (randomized and took at least 1 dose of study drug) and 394 subjects were included in full analysis set (had at least 1 efficacy evaluation).

Participants by arm

Arm	Count
Paliperidone Extended Release (ER) Paliperidone ER 3 milligram (mg) or 6 mg or 9 mg or 12 mg oral tablets depending on Investigator's discretion once daily for 12 weeks.	394
Total	394

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	15
Overall Study	Lack of Efficacy	12
Overall Study	Lost to Follow-up	21
Overall Study	Other	6
Overall Study	Protocol Violation	6
Overall Study	Study medication non-compliance	3
Overall Study	Withdrawal by Subject	14

Baseline characteristics

Characteristic	Paliperidone Extended Release (ER)
Age Continuous	30.88 Years STANDARD_DEVIATION 10.39
Sex: Female, Male Female	199 Participants
Sex: Female, Male Male	195 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	227 / 403
serious Total, serious adverse events	1 / 403

Outcome results

Primary

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12

PANSS is a medical scale that assesses various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions \[a false belief held in the face of strong differing evidence, especially as a symptom of psychiatric disorder\] and hallucinations \[imagining things\], and withdrawal into the self). The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).