Safety, Efficacy and Tolerability Study of Paliperidone Extended-Release (ER) in Participants 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 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01662648

Enrollment

1117

Registered

2012-08-10

Start date

2007-06-30

Completion date

2009-04-30

Last updated

2014-05-05

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

Conditions

Schizophrenia

Keywords

Schizophrenia, Paliperidone, Paliperidone extended-release (ER)

Brief summary

The purpose of this study is to explore the efficacy of flexibly dosed paliperidone extended-release (ER) in 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 previously unsuccessfully treated with other oral antipsychotics.

Detailed description

This is a single arm (one group of participants), multi-center, 6-month study to explore the tolerability, safety and efficacy of flexibly dosed paliperidone ER in participants with schizophrenia previously unsuccessfully treated with an oral antipsychotic medication. Antipsychotic medications are drugs that are helpful in the treatment of psychosis and have a capacity to ameliorate thought disorders. Unsuccessfully treated means that, despite the participant was treated with an adequate dose of an appropriate oral antipsychotic for an adequate period of time, previous treatment is considered unsuccessful due to lack of efficacy, lack of tolerability or safety, lack of compliance and/or other reasons. Throughout the study the investigators will adjust the dosage of each participant based on the individual needs. In general, the recommended paliperidone ER dose will be 6 milligram once daily. Participants can be either in- or outpatients and they may take their study drug with or without food. Participants who will complete this 6-month study and would like to continue will be eligible to be enrolled in an extension phase until paliperidone ER is available.

Interventions

DRUGPaliperidone ER

Paliperidone extended-release (ER) tablet in dose range of 3 to 12 milligram (mg) per day will be given orally for 6 months as per Investigator's discretion.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participant diagnosed with schizophrenia * Participant's previous treatment of schizophrenia is considered unsuccessful * Participant is healthy on the basis of a physical examination and vital signs * Women must be postmenopausal, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study * Be willing and able to fill out self-administered questionnaires

Exclusion criteria

* Have used clozapine or Risperdal CONSTA during the last month, or have received any other conventional drug used to treat psychosis during the last 3 months * 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 * Pregnant or breast-feeding female * History or current symptoms of tardive dyskinesia (involuntary movements of the facial muscles and tongue)

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 26	Baseline and Week 26	The PANSS is a 30-item scale 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 and ranges from 30 to 210. Higher scores indicate worsening. Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.

Secondary

Measure	Time frame	Description
Percentage of Participants With Greater Than or Equal to 20 Percent (%) Improvement in PANSS Total Score at Week 26	Week 26	The PANSS is a 30-item scale 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 and ranges from 30 to 210. Higher scores indicate worsening. Percentage of participants with greater than or equal to 20 % improvement in PANSS total score is reported here. Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in PANSS Total Positive Subscale Score at Week 26	Baseline and Week 26	The Positive Subscale of PANSS (Positive and Negative Syndrome Scale) assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess of or distortion of normal functions. The symptoms are rated on a 7-point scale, ranging from 7 (absent) to 49 (extreme psychopathology). Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in PANSS Total Negative Subscale Score at Week 26	Baseline and Week 26	The Negative Subscale of PANSS (Positive and Negative Syndrome Scale) 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, ranging from 7 (absent) to 49 (extreme psychopathology). Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 26	Baseline and Week 26	The CGI 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 indicates to normal, not at all ill and a rating of 7 indicates among the most extremely ill participants. Higher scores indicate worsening. Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in Personal and Social Performance (PSP) Scale at Week 26	Baseline and Week 26	The PSP scale assesses the degree of 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. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less or equal to 30, functioning so poorly as to require intensive supervision. Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in Sleep Quality at Week 26	Baseline and Week 26	Sleep quality was assessed by an 11-point visual analog scale that rates how well participants sleep. Participants indicated on the scale (from 0 to 100 millimeter) how well they have slept in the previous 7 days (from 0: very badly to 100: very well). Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Change From Baseline in Daytime Drowsiness at Week 26	Baseline and Week 26	Daytime Drowsiness was assessed by an 11-point visual analog scale that rates how well participants sleep. Participants indicated on the scale (from 0 to 100 millimeter) how often they have felt drowsy within the previous 7 days (from 0: not at all to 100:all the time). Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.
Number of Participants Within Each Category of Patient Satisfaction Score	Baseline and Week 26	Participants were interviewed at baseline and at the end of the trial (Week 26) to assess their satisfaction with the current treatment on a 5-point scale (very good, good, reasonable, moderate or poor). Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.

Participant flow

Participants by arm

Arm	Count
Paliperidone ER: Lack of Efficacy Paliperidone extended-release (ER) tablet in dose range of 3 to 12 milligram (mg) per day was given orally for 6 months as per Investigator's discretion to participants who transitioned to Paliperidone ER from other oral antipsychotics for the main reason of lack of efficacy.	520
Paliperidone ER: Lack of Tolerability, Compliance or Other Paliperidone extended-release (ER) tablet in dose range of 3 to 12 milligram (mg) per day was given orally for 6 months as per Investigator's discretion to participants who transitioned to Paliperidone ER from other oral antipsychotics for the main reason of lack of tolerability, compliance or other reasons.	597
Total	1,117

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	40	37
Overall Study	Adverse event and lack of efficacy (LOE)	3	0
Overall Study	Death	1	3
Overall Study	Lack of Efficacy	17	16
Overall Study	LOE and other reason unspecified	1	0
Overall Study	LOE and Participant non-compliant	0	1
Overall Study	Lost to Follow-up	24	36
Overall Study	Other	8	11
Overall Study	Participant ineligible to continue trial	1	1
Overall Study	Participant non-compliant	16	20
Overall Study	Withdrawal by Subject	36	53

Baseline characteristics

Characteristic	Paliperidone ER: Lack of Efficacy	Total	Paliperidone ER: Lack of Tolerability, Compliance or Other
Age, Customized >= 35 to < 45 years	152 Participants	304 Participants	152 Participants
Age, Customized >= 45 to < 55 years	83 Participants	170 Participants	87 Participants
Age, Customized >= 55 to < 65 years	33 Participants	67 Participants	34 Participants
Age, Customized >= 65 to < 75 years	6 Participants	13 Participants	7 Participants
Age, Customized Greater than 75 years	1 Participants	2 Participants	1 Participants
Age, Customized Greater than or equal to (>=) 25 to < 35 years	153 Participants	344 Participants	191 Participants
Age, Customized Less than (<) 25 years	92 Participants 11.63	217 Participants	125 Participants 11.9
Sex: Female, Male Female	192 Participants	460 Participants	268 Participants
Sex: Female, Male Male	328 Participants	657 Participants	329 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	208 / 512	239 / 587
serious Total, serious adverse events	35 / 512	29 / 587

Outcome results

Primary

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 26

The PANSS is a 30-item scale 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 and ranges from 30 to 210. Higher scores indicate worsening. Data for two groups is presented here, based on the reason to switch: lack of efficacy and lack of tolerability, compliance or other who switched from other previous antipsychotic drugs to paliperidone.