Evaluation of Effectiveness and Safety of Flexible-dose Paliperidone Extended Release in Patients With Schizoaffective Disorder.

This study has been completed.
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00412373
First received: December 15, 2006
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to measure the effectiveness and assess the safety of different dosages (from 3 mg/day to 12 mg/day) of the antipsychotic paliperidone extended-release (ER) in patients who are experiencing an acute episode of schizoaffective disorder.


Condition Intervention Phase
Schizoaffective Disorder
Psychotic Disorder
Drug: Placebo
Drug: Paliperidone ER
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: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel- Group Study to Evaluate the Efficacy and Safety of Flexible-dose Paliperidone ER in the Treatment of Patients With Schizoaffective Disorder.

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale (range 30-210) 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. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: The primary efficacy endpoint was the change from baseline to week 6 or the last post-randomization assessment during double-blind treatment in the PANSS total score. ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale (range 30-210) 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. Higher scores indicate worsening.


Secondary Outcome Measures:
  • Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Positive Syndrome Scale (range 7-49): Sum of scores for items 1-7 in positive subscale: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Negative Syndrome Scale (range 7-49): Sum of scores for items 1-7 in negative subscale: blunted effect, emotional withdrawal, poor rapport, passive apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    General Psychopathology (range 16-112): Sum of scores for somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Positive PANSS Factor Score (range 8-56): Sum of scores for items 1, 3, 5, and 6 in positive subscale: delusions, hallucinatory behavior, grandiosity, suspiciousness; item 7 in negative subscale: stereotyped thinking; and items 1, 9, and 12 in general psychopathology subscale: somatic concern, unusual thought content, lack of judgment, and insight. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Negative PANSS Factor Score (range 7-49): Sum of scores for items 1, 2, 3, 4, and 6 in negative subscale: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity; and items 7 and 16 in general psychopathology subscale: motor retardation, and active social avoidance. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Disorganized Thoughts PANSS Factor Score (range 7-49): Sum of scores for item 2 in positive subscale:Conceptual disorganization; item 5 in negative subscale:difficulty in abstract thinking; and items 5, 10, 11, 13, and 15 in general psychopathology subscale: mannerisms/posturing, disorientation, poor attention, disturbance of volition, and preoccupation. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Uncontrolled Hostility/Excitement PANSS Factor Score (range 4-28): Sum of scores for items 4 and 7 in positive subscale: excitement, hostility; and items 8 and 14 in general psychopathology subscale: uncooperativeness, and poor impulse control. Higher scores indicate worsening.

  • Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Anxiety/Depression PANSS Factor Score (range 4-28): Sum of scores for items 2, 3, 4, and 6 in general psychopathology subscale: Anxiety, Guilt feelings, Tension, Depression. Higher scores indicate worsening.

  • Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 subject. 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 subjects". Higher scores indicate worsening.

  • Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    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 subject. 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 subjects". Higher scores indicate worsening.

  • Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder [ Time Frame: Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    The CGI-C rating scale is a 7 point global assessment that measures the clinician's impression of the change occurring in the illness over a course of treatment, relative to baseline. A rating of 4 is equivalent to "No change". Ratings of <4 are equivalent to "improvement" and ratings of > 4 are equivalent to "worsening". Higher scores indicate worsening.

  • Participants With Response [ Time Frame: Week 6 LOCF End Point ] [ Designated as safety issue: No ]
    Response is defined as a 30% or more reduction from baseline PANSS total score and CGI-C score of <= 2 (CGI-C-SCA: Clinical Global Impression of Change for Schizoaffective Disorder).


Other Outcome Measures:
  • Baseline Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on either a 5-point (0 to 4) or a 3-point (0 to 2) scale. The 5-point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. The responses are summed to yield the HAM-D-21 score that ranges from 0-63.

  • Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    Clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on either a 5-point (0 to 4) or a 3-point (0 to 2) scale. The 5-point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. The responses are summed to yield the HAM-D-21 score that ranges from 0-63.

  • Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    11-item scale (elevated mood, increased motor activity, sexual interest, sleep, irritability, speech [rate/amount], language-thought disorder, content, disruptive-aggressive behaviors, appearance, and insight) based on subject's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. The responses are summed to yield the YMRS total score, which ranges from 0 to 60.

  • Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. [ Time Frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment ] [ Designated as safety issue: No ]
    11-item scale (elevated mood, increased motor activity, sexual interest, sleep, irritability, speech [rate/amount], language-thought disorder, content, disruptive-aggressive behaviors, appearance, and insight) based on subject's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. The responses are summed to yield the YMRS total score, which ranges from 0 to 60.


Enrollment: 307
Study Start Date: December 2006
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Paliperidone ER (3-12mg/day in 3 mg/day increments for 6 weeks)
Drug: Paliperidone ER
(3-12mg/day in 3 mg/day increments for 6 weeks)
Experimental: 003
Paliperidone ER (3-12mg/day in 3 mg/day increments for 6 weeks)
Drug: Paliperidone ER
(3-12mg/day in 3 mg/day increments for 6 weeks)
Placebo Comparator: 002
Placebo for 6 weeks
Drug: Placebo
for 6 weeks

Detailed Description:

Schizophrenia and schizoaffective disorder are closely related in terms of symptoms, coexisting conditions, and genetic risk. In previous studies in patients with schizophrenia, treatment with paliperidone extended-release (ER) improved psychotic symptoms, as well as mood symptoms evaluated by anxiety/depression and hostility/excitement Positive and Negative Symptoms of Schizophrenia (PANSS) factor scores. Therefore, paliperidone ER may also be effective in treating symptoms of schizoaffective disorder. Paliperidone's limited potential for drug-drug interaction is particularly important in this patient population, in which multiple drug therapy is relatively common. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo-controlled, parallel-group study is designed to examine the effectiveness and safety of paliperidone ER in adult patients with schizoaffective disorder who are experiencing an acute episode of this disorder. Patients in the study will be randomly assigned to 1 of 2 groups to receive 6 weeks of oral treatment with flexible dosages of paliperidone ER (3-12 mg/day) or with placebo. The primary efficacy outcome will be the change from baseline to Week 6, or the last post-randomization assessment during double-blind treatment (endpoint), in the PANSS total score. Safety will be assessed by monitoring adverse events, clinical laboratory testing, pregnancy testing, vital signs measurements, physical examination, administration of a 12-lead ECG, movement disorders side effect scales, and the InterSePT Scale for Suicidal Thinking. Patients may also choose to participate in a pharmacogenomic (DNA) analysis. The primary study hypothesis is that flexible-dose paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder. Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or paliperidone ER 6 mg/day. After day 4, dosages may be adjusted, at defined intervals, to a dosage between 3 mg/day and 12 mg/day, inclusive.

  Eligibility

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

Inclusion Criteria:

  • Diagnostic and Statistical Manual - Fourth Edition (DSM-IV) diagnosis of schizoaffective disorder
  • A total Positive and Negative Symptoms of Schizophrenia (PANSS) score of >= 60
  • A score of >= 16 on Young Mania Rating Scale (YMRS) or a score of >= 16 on the Hamilton Depression Rating Scale (HAM-D 21)

Exclusion Criteria:

  • A primary active mental illness diagnosis other than schizoaffective disorder
  • Patients with first episode psychosis
  • Active substance dependence within previous 6 months
  • Treatment with clozapine within 6 months of randomization
  • A history of treatment resistance, defined by failure to respond to 2 adequate trials of antipsychotic medication
  • Pregnancy, 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: NCT00412373

  Show 44 Study Locations
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Janssen, LP
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00412373     History of Changes
Other Study ID Numbers: CR013099, R076477SCA3002
Study First Received: December 15, 2006
Results First Received: July 1, 2009
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizoaffective Disorder
antipsychotic
paliperidone
placebo

Additional relevant MeSH terms:
Disease
Mental Disorders
Psychotic 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 October 30, 2014