A Study to Evaluate the Efficacy of Paliperidone Palmitate in the Prevention of Relapse of the Symptoms of Schizoaffective Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:
NCT01193153
First received: August 30, 2010
Last updated: December 22, 2014
Last verified: December 2014
  Purpose

This study will evaluate the efficacy of paliperidone palmitate compared with placebo in the delay of relapse of the symptoms of schizoaffective disorder. This study will also assess the safety and tolerability of paliperidone palmitate in patients with schizoaffective disorder.


Condition Intervention Phase
Schizoaffective Disorder
Drug: Placebo
Drug: paliperidone palmitate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parellel-Group Study of Paliperidone Palmitate Evaluating Time to Relapse in Subjects With Schizoaffective Disorder

Resource links provided by NLM:


Further study details as provided by Janssen Scientific Affairs, LLC:

Primary Outcome Measures:
  • Double-blind: Percentage of Participants Who Experienced Relapse [ Time Frame: Day 1 up to Month 15 of double blind relapse prevention period ] [ Designated as safety issue: No ]
    Relapse was defined as first occurrence of any 1 of following:psychiatric hospitalization due to worsening symptoms; any intervention employed to avert imminent hospitalization due to worsening symptoms or need for additional antipsychotic,antidepressants/mood stabilizing medication; deliberate self-injury,suicidal/homicidal ideation that is clinically significant as determined by investigator,or violent behavior resulting in clinically significant injury to another person or property damage; worsening of any 1 or more of 8 selected positive and negative syndrome scale(PANSS) items to a score of greater than or equal to (>= 6) after randomization(if the score for the corresponding item was less than or equal to [<=] 4 at randomization); worsening of certain other measures in specific ways at 2 consecutive visits. Relapse by subgroup of participants on monotherapy,adjunctive therapy to antidepressants/mood stabilizers,participants with psychotic symptoms/mood symptoms was examined.


Secondary Outcome Measures:
  • Double-blind: Change From Baseline in Personal and Social Performance (PSP) Total Score at Week 64 (Total Mixed Model Repeated Measures [MMRM] Analysis of Covariance [ANCOVA]) [ Time Frame: Baseline and Week 64 of double blind relapse prevention period ] [ Designated as safety issue: No ]
    The PSP scale was designed to assess the degree of dysfunction a participant exhibits during a month prior to any visit within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior, each 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. A score lying between 71 and 100 indicated a good functioning; one between 31 and 70 indicated varying degrees of difficulty, and a score of <=30 indicated functioning so poor that participant required intensive supervision.

  • Open-label: Change From Baseline in Personal and Social Performance (PSP) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 13/LOCF) in Open-label (OL) Lead-in period, Endpoint (Week 25/LOCF) in open-label stabilization period ] [ Designated as safety issue: No ]
    The PSP scale was designed to assess the degree of dysfunction a participant exhibits during a month prior to any visit within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior, each 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. A score lying between 71 and 100 indicated a good functioning; one between 31 and 70 indicated varying degrees of difficulty, and a score of <=30 indicated functioning so poor that participant required intensive supervision.

  • Double-blind: Change From Baseline in Personal and Social Performance (PSP) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in double-blind period ] [ Designated as safety issue: No ]
    The PSP scale was designed to assess the degree of dysfunction a participant exhibits during a month prior to any visit within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior, each 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. A score lying between 71 and 100 indicated a good functioning; one between 31 and 70 indicated varying degrees of difficulty, and a score of <=30 indicated functioning so poor that participant required intensive supervision.

  • Double-blind: Number of Participants With Personal and Social Performance (PSP) Categorical Scores [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in DB period ] [ Designated as safety issue: No ]
    The PSP scale was designed to assess the degree of dysfunction a participant exhibits during a month prior to any visit within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior, each 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. Number of participants in each specific category; good functioning (PSP total score >70), variable functioning (PSP total score between 31 and 70), and poor functioning (PSP total score <=30) were assessed.

  • Open-label: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 13/LOCF) in OL Lead-in period, Endpoint (Week 25/LOCF) in open-label stabilization period ] [ Designated as safety issue: No ]
    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.

  • Double-blind: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in double-blind period ] [ Designated as safety issue: No ]
    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.

  • Open-label: Change From Baseline in Hamilton Rating Scale for Depression (HAM-D-21) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 13/LOCF) in OL Lead-in period, Endpoint (Week 25/LOCF) in open-label stabilization period ] [ Designated as safety issue: No ]
    The HAM-D-21 is a 21-item, clinician-rated scale to evaluate depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on a 5-point (0 to 4) scale. The 5-point scale items use a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A rating of 4 is usually reserved for extreme symptoms. The responses for all 21 items are summed to yield the HAM-D-21 total score that ranges from 0-63.

  • Double-blind: Change From Baseline in Hamilton Rating Scale for Depression (HAM-D-21) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in double-blind period ] [ Designated as safety issue: No ]
    The HAM-D-21 is a 21-item, clinician-rated scale to evaluate depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on a 5-point (0 to 4) scale. The 5-point scale items use a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A rating of 4 is usually reserved for extreme symptoms. The responses for all 21 items are summed to yield the HAM-D-21 total score that ranges from 0-63.

  • Open-label: Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 13/LOCF) in OL Lead-in period, Endpoint (Week 25/LOCF) in open-label stabilization period ] [ Designated as safety issue: No ]
    The YMRS was designed to measure the severity of manic symptoms, to gauge the effect of treatment on mania severity, and to detect a return of manic symptoms (for example relapse or recurrence). YMRS is a checklist of 11 items that are ranked on a scale of 0 to 4 or 0 to 8. Seven of the items (elevated mood, increased motor activity, sexual interest, sleep, language-thought disorder, appearance, and insight) are ranked 0 to 4 and have descriptors associated with each severity level (that is, 0, 1, 2, 3, 4). Four of the items (irritability, speech, content, and disruptive-aggressive behavior) are scored 0 to 8 and have descriptors for every other increment (that is, 0, 2, 4, 6, 8). The item score is based on participant's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. Responses are summed to yield YMRS total score ranging from 0 to 60.

  • Double-blind: Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in double-blind period ] [ Designated as safety issue: No ]
    The YMRS was designed to measure the severity of manic symptoms, to gauge the effect of treatment on mania severity, and to detect a return of manic symptoms (for example relapse or recurrence). YMRS is a checklist of 11 items that are ranked on a scale of 0 to 4 or 0 to 8. Seven of the items (elevated mood, increased motor activity, sexual interest, sleep, language-thought disorder, appearance, and insight) are ranked 0 to 4 and have descriptors associated with each severity level (that is, 0, 1, 2, 3, 4). Four of the items (irritability, speech, content, and disruptive-aggressive behavior) are scored 0 to 8 and have descriptors for every other increment (that is, 0, 2, 4, 6, 8). The item score is based on participant's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. Responses are summed to yield YMRS total score ranging from 0 to 60.

  • Open-label: Change From Baseline in Clinical Global Impression - Severity Schizoaffective Scale (CGI-S-SCA) Overall Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 13/LOCF) in OL Lead-in period, Endpoint (Week 25/LOCF) in open-label stabilization period ] [ Designated as safety issue: No ]
    The CGI-S-SCA is a syndrome-specific 7-point scale (from 1 indicating not ill to 7 indicating very severely ill) that includes an overall severity score as well as scores for the positive, negative, manic, and depressive domains of the illness. The CGI-S-SCA was used to assess the level of overall impairment, as well as that related to each domain, at the time of the visit and for the week prior to the visit".

  • Double-blind: Change From Baseline in Clinical Global Impression - Severity Schizoaffective Scale (CGI-S-SCA) Overall Score at Endpoint [ Time Frame: Baseline and Endpoint (Week 64/LOCF) in double-blind period ] [ Designated as safety issue: No ]
    The CGI-S-SCA is a syndrome-specific 7-point scale (from 1 indicating not ill to 7 indicating very severely ill) that includes an overall severity score as well as scores for the positive, negative, manic, and depressive domains of the illness. The CGI-S-SCA was used to assess the level of overall impairment, as well as that related to each domain, at the time of the visit and for the week prior to the visit".


Enrollment: 667
Study Start Date: September 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
paliperidone palmitate 78 117 156 234 mg (50 75 100 or 150 mg eq.) monthly by i.m. injection for 15 months
Drug: paliperidone palmitate
78, 117, 156, 234 mg (50, 75, 100, or 150 mg eq.) monthly by i.m. injection for 15 months
Placebo Comparator: 002
Placebo monthly by i.m. injection for 15 months
Drug: Placebo
monthly by i.m. injection for 15 months

Detailed Description:

Schizoaffective disorder is a chronic illness and generally requires life-long treatment. To date however, no medication has been evaluated in the maintenance treatment of schizoaffective disorder. This is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of paliperidone palmitate, as monotherapy or as an adjunct to mood stabilizers or antidepressants, relative to placebo in delaying the time to relapse in patients with schizoaffective disorder. This study explores the use of paliperidone palmitate either as monotherapy or as an adjunct to mood stabilizers or antidepressants (MS/AD) because both treatment approaches are commonly used in the clinical management of schizoaffective disorder. Patients with acute symptoms of schizoaffective disorder will be enrolled. The study will consist of 4 periods: an up to 7 days screening/tolerability period, a 13-week open-label flexible dose lead-in period, a 12-week open-label fixed dose stabilization period, and a 15 months double-blind relapse prevention period. Patients without previous exposure to paliperidone ER (Invega), paliperidone palmitate (Invega Sustenna), risperidone, or RISPERDAL CONSTA will be given 4 to 6 days of paliperidone ER 6mg/day for tolerability testing. Patients can continue their current antipsychotic regimen through Day -1 (the day before the start of the study period). During the open-label periods, all patients will be treated with paliperidone palmitate. An initial loading dose of 234 mg (150 mg eq.) of paliperidone palmitate will be given by deltoid injection followed by 156 mg (100 mg eq.) deltoid injection on Day 8. Starting on Day 36, injections may be administered in either the deltoid muscle or the gluteal muscle. Doses at Days 36, 64 and 92 may be increased or decreased within the range of 78 mg (50 mg eq.) and 234 mg (150 mg. eq.) as clinically indicated. Dose will be fixed (at Day 92 dose) during the 12-week stabilization period. Patients who meet pre-determined stabilization criteria will be eligible to enter the double-blind relapse prevention period and will be randomly assigned to either receive paliperidone palmitate (at the Day 92 dose) or placebo treatment. Patients will have intramuscular (i.m.) study drug injection and efficay and saftety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated during the study using a relapse assessment, the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression of Severity for Schizoaffective Disorder (CGI-S-SCA), the Personal and Social Performance Scale (PSP), the Young Mania Rating Scale (YMRS), and the Hamilton Rating Scale for Depression (HAM-D). Safety will be assessed throughout the study by monitoring of adverse events, clinical laboratory tests, electrocardiograms (ECGs), vital sign measurements (temperature, pulse, and blood pressure), weight, and the monitoring of extrapyramidal symptoms using the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A). Suicidality will be assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). A 10 milliliter pharmacogenomic blood sample (sample for DNA research) will be collected from patients who give separate written informed consent for this part of the study. Participation in pharmacogenomic research is optional. Blood samples will be taken from patients being treated with lithium or valproate for the measurement of blood lithium or valproate levels. Approximately 52 mL (31 mL for patients who are not receiving lithium or valproate) of whole blood will be collected during the study. All patients will receive paliperidone palmitate 78, 117, 156, 234 mg (50, 75, 100, or 150 mg eq.) monthly by i.m. injection for the the first 25 weeks of the study (open-label periods). During the 15-month double-blind relapse prevention period, one half of the patients will be randomized to paliperidone palmitate treatment (50, 75, 100, or 150 mg eq. monthly i.m. injection) and the other half of the patients will be randomized to monthly placebo injection.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of schizoaffective disorder
  • Experiencing an acute exacerbation of psychotic symptoms
  • A score of >=4 on at least 3 of the following 7 PANSS items: Delusions (P1), Hallucinatory behavior (P3), Excitement (P4), Hostility (P7), Tension (G4), Uncooperativeness (G8), and Poor Impulse Control (G14)
  • A score of >=16 on YMRS and/or a score of >=16 on the HAM-D-21
  • Healthy based on physical examinations, electrocardiogram (ECG), laboratory tests, medical history, and vital signs measurements

Exclusion Criteria:

  • A primary active mental illness diagnosis other than schizoaffective disorder
  • Have attempted suicide within 12 months or are at imminent risk of suicide or violent behavior
  • Subjects with first episode of psychosis
  • Received electroconvulsive therapy in the past 3 months
  • History of hypersensitivity to or intolerance of paliperidone, risperidone, or 20% Intralipid (placebo)
  • Received long-acting antipsychotic medication within 2 injection cycles
  • Received therapy with clozapine within 3 months
  • A history of neuroleptic malignant syndrome
  • Previous history of lack of response to antipsychotic medication
  • Subjects receiving therapy with antidepressants or mood stabilizers that has been initiated and/or changed in dose <30 days prior to screening
  • Receiving therapy with carbamazepine
  • Receiving therapy with monoamine oxidase inhibitors
  • Pregnant, breast-feeding, or planning to become pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01193153

  Show 84 Study Locations
Sponsors and Collaborators
Janssen Scientific Affairs, LLC
Investigators
Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC
  More Information

No publications provided by Janssen Scientific Affairs, LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier: NCT01193153     History of Changes
Other Study ID Numbers: CR016618, R092670SCA3004
Study First Received: August 30, 2010
Results First Received: December 22, 2014
Last Updated: December 22, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
India: Ministry of Health
Malaysia: Ministry of Health
Philippines: Bureau of Food and Drugs
Romania: National Medicines Agency
South Africa: Medicines Control Council
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Janssen Scientific Affairs, LLC:
schizoaffective disorder
paliperidone palmitate
INVEGA SUSTENNA
schizoaffective disorder relapse prevention

Additional relevant MeSH terms:
Disease
Psychotic Disorders
Mental Disorders
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
9-hydroxy-risperidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on June 30, 2015