An Efficacy and Safety Study of Paliperidone Extended-Release (ER) Tablets in Participants With Schizophrenia (PERTAIN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT00566631
First received: November 29, 2007
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to evaluate the tolerability, safety and treatment response of flexible doses of paliperidone extended-release (ER; designed to slowly release a drug in the body over an extended period of time) tablets in participants with acute schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tolerability, Safety and Treatment Response of Flexible Doses of Paliperidone ER in Acutely Exacerbated Subjects With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • Number of Participants With Treatment Response Based on Total PANSS Scale Score [ Time Frame: Day 42 or early discontinuation ] [ Designated as safety issue: No ]
    Response was defined as decrease of at least 30 percent in total Positive and Negative Syndrome Scale (PANSS) score from Baseline to endpoint of core phase (which is, Day 42 or early discontinuation). The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, & 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 sum of all 30 PANSS items & ranges from 30 to 210. Higher scores indicate worsening.


Secondary Outcome Measures:
  • Change From Baseline in Total Positive and Negative Symptom Scale (PANSS) Score at Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ 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. Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Day 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale to assess 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 and disorganized thoughts subscale, consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement (H/E) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity. Final evaluation is the last post-baseline visit with data.

  • Percentage of Participants With Treatment Response Greater Than (>) 20 Percent, 40 Percent and 50 Percent in Total Positive and Negative Syndrome Scale (PANSS) Score [ Time Frame: Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ 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. Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Clinical Global Impression -Severity (CGI-S) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ 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 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 scores indicate worsening. Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Personal and Social Performance Scale (PSP) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: No ]
    The PSP assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal & social relationships, self-care & 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 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 than or equal to 30, functioning so poorly as to require intensive supervision. Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Quality of Sleep Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: No ]
    The sleep evaluation scale is a self-administered scale that rates quality of sleep. Participants indicate on an 11-point scale that how well they have slept within the previous 7 days, score ranged from 0 (very badly) to 10 (very well). Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Day Time Drowsiness Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: No ]
    The day time drowsiness evaluation scale is a self-administered scale that rates day time drowsiness. Participants indicate on an 11-point scale that how often they have felt drowsy within the previous 7 days, score ranged from 0 (not at all) to 10 (all the time). Final evaluation is the last post-baseline visit with data.

  • Number of Participants Satisfied With the Study Treatment [ Time Frame: Day 42 or early discontinuation ] [ Designated as safety issue: No ]
    Treatment satisfaction with paliperidone ER was assessed by the Investigator and participant on a 5-point scale: 1 (very good), 2 (good), 3 (reasonable), 4 (moderate) and 5 (poor), at the end of the core treatment phase (which is, Day 42 or early discontinuation) by conducting an interview.


Other Outcome Measures:
  • Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: Yes ]
    The AIMS is a 12-item scale to provide a numeric measure to the observed abnormal movements in different parts of the body. Information is collected after a brief neurological examination and is scored on a 5-point scale (0=none and 4=severe). Final evaluation is the last post-baseline visit with data.

  • Change From Baseline in Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: Yes ]
    The SAS is a 10-item scale used to measure the symptoms of parkinsonism (slow movements) or parkinsonian side-effects related to the use of antipsychotic medications. The SAS rates 10 items (including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, Glabella tap, tremor and salivation), score ranging from 0 (normal) to 4 (extreme). The SAS global score is the average score (total sum of items score divided by the number of items) and ranges between 0 and 4, where the higher score indicates more severe condition of Extrapyramidal Symptoms. Final evaluation is the last post- baseline visit with data.

  • Change From Baseline in Global Rating Sub-scale Score Based on Barnes Akathisia Rating Scale (BARS) at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation) [ Time Frame: Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation) ] [ Designated as safety issue: Yes ]
    The BARS included an objective rating (from 0=normal to 3=constantly engaged), two subjective ratings of symptoms of akathisia, namely awareness of restlessness (ranging from 0=absence of inner restlessness to 3=awareness of intense compulsion to move) and reported distress related to restlessness (ranging from 0=no distress to 3=severe), and a global clinical rating of akathisia, ranging from 0 (absent) to 5 (severe). Global rating sub-scale score (that is, global clinical rating of akathisia) was assessed which was scored separately and is the most relevant measure of severity of akathisia. Higher scores indicates worsening akathisia. Final evaluation is the last post-baseline visit with data.


Enrollment: 294
Study Start Date: July 2007
Study Completion Date: May 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paliperidone Extended Release (ER) Drug: Paliperidone
Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion will be given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.
Other Name: Invega

Detailed Description:

This is an open-label (all people know the identity of the intervention), single-arm (getting one dose of medicine), multi-center (conducted in more than 1 center) study to evaluate tolerability, safety and efficacy of flexible daily doses of paliperidone ER in participants with acute schizophrenia. All participants will be given paliperidone ER once daily at a dose of 3, 6, 9, or 12 milligram (mg) tablets orally depending on Investigator's discretion, based on participant's clinical response and tolerability towards paliperidone ER. The duration of the core phase of the treatment will be 6 weeks and the participants who will complete this phase, respond well and would like to continue, will be eligible to be enrolled in an extension phase, which is no longer than 12 months. Efficacy will primarily be evaluated by treatment response evaluated through total Positive and Negative Syndrome Scale (PANSS) score. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia
  • Must be experiencing an acute schizophrenic episode with a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 70 at Baseline
  • Must be admitted to hospital for treatment of the acute schizophrenic episode and must agree for voluntary hospitalization for at least the first 7 days of the study
  • Female participants must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and female participants of child-bearing potential must have a negative urine pregnancy test at Screening
  • Participants or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

  • Pregnant or breast-feeding female participants
  • First antipsychotic treatment ever
  • Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment and on clozapine or a long-acting injectable antipsychotic during the last 3 months
  • Known hypersensitivity to paliperidone extended-release (ER) or risperidone
  • Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome including recent or present clinically relevant laboratory abnormalities (as deemed by the Investigator) and participants with current or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria
  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: NCT00566631

Locations
Croatia
Zagreb, Croatia
France
Dieppe N/A, France
La Charite Sur Loire, France
Metz Cedex 01, France
Germany
Augsburg, Germany
Bonn, Germany
Mainz, Germany
Mannheim, Germany
München, Germany
Rostock, Germany
Wasserburg, Germany
Israel
Be-Er Ya-Acov, Israel
Beer Sheva, Israel
Hod-Hasharon, Israel
Pardesia, Israel
Ramat Gan, Israel
Lithuania
Klaipeda, Lithuania
Siauliai, Lithuania
Vilnius, Lithuania
Poland
Gda Sk Poland, Poland
Lublin, Poland
Lubliniec, Poland
Skape, Poland
Swiecie, Poland
Torun N/A, Poland
Zabki, Poland
Łódź, Poland
Romania
Bucharest, Romania
Cluj-Napoca, Romania
Craiova, Romania
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV, Belgium Clinical Trial Janssen-Cilag International NV
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00566631     History of Changes
Other Study ID Numbers: CR013162, R076477SCH3018
Study First Received: November 29, 2007
Results First Received: April 3, 2013
Last Updated: June 27, 2013
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment
Croatia: Ministry of Health and Social Care

Keywords provided by Janssen-Cilag International NV:
Schizophrenia
Paliperidone Extended Release (ER)
Invega

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

ClinicalTrials.gov processed this record on August 21, 2014