An Inpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Treatment Of Acute Exacerbation Of Schizophrenia

Study Overview
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Brief Summary
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This study aims to evaluate whether PF-02545920 is safe and effective in the treatment of acute exacerbation of schizophrenia during a 4-week inpatient treatment period. The study will use the Positive and Negative Syndrome Scale (PANSS) to measure change in symptoms for PF-02545920 compared to risperidone and placebo treatment.

Official Title
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A Phase 2, Multicenter, Double-blind, Randomized, Parallel Group, 4-week Inpatient Study To Evaluate The Safety And Efficacy Of Two Fixed Doses Of Pf-02545920 Compared To Placebo In The Treatment Of Acute Exacerbation Of Schizophrenia Using Risperidone As An Active Control

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: PF-02545920
* Drug: PF-02545920
* Drug: Placebo
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia with acute exacerbation of illness The current acute exacerbation of schizophrenia must be less than 4 weeks duration prior to the initial evaluation. Exclusion Criteria: Subjects with evidence or history of clinically significant uncontrolled medical illness Subjects with a current diagnosis of schizoaffective disorder, major depression, bipolar disorder, or obsessive compulsive disorder. Subjects who meet Diagnostic and Statistical Manual-IV (DSM-IV)defined diagnostic criteria for psychoactive substance dependence (excluding nicotine dependence) within 12 months of screening or DSM-IV defined substance abuse within 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-02545920 5 mg<br> | Drug: PF-02545920<br>* 5 mg tablet every 12 hours for 28 days<br>|
| Experimental: PF-02545920 15 mg<br> | Drug: PF-02545920<br>* 15 mg tablet every 12 hours for 28 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One tablet/capsule every 12 hours for 28 days<br>|
| Active Comparator: Risperidone 3 mg<br> | Drug: Risperidone<br>* 3 mg capsule every 12 hours for 28 days<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. | Baseline, Week 4 | 
| Proportion of Participants With Dystonia Adverse Events | Participants were assessed for presence of symptoms for any one of the following: dystonia, oromandibular dystonia, and oculogyric crisis. | Baseline up to end of study (7 to 10 days after administration of last dose of study medication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive, Negative, and General Subscales Score at Week 4 | PANSS - positive, negative, and general subscales assesses positive, negative and general psychopathological symptoms associated with schizophrenia respectively. Seven (7) items each make up the positive scale (for example; delusions, conceptual disorganization, and hallucinatory behavior) and negative scale (for example; blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal) and 16 items make up the general scale (for example; somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, pre-occupation). Each item is rated on a 7-point Likert scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total scores range for positive as well as negative subscale is 7 to 49 and for general subscale is 16 to 112; higher subscale score indicates greater severity. | Baseline, Week 4 | 
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 4 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state. Clinician responded to a question Considering your total clinical experience with this particular population, how mentally ill is your patient at this time? on the following scores: 1 (normal - not ill at all), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most severely ill participants). Higher score = more affected. | Baseline, Week 4 | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Marder Factors Score at Week 4 | 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). PANSS Marder positive symptoms subscale consists of 8 items with total score equal to sum of 8 items ranging from 8-56; Marder negative symptoms subscale and Marder disorganized thoughts (Dis. Thought) subscale, each consists of 7 items with total score equal to sum of 7 items each, ranging from 7-49, Marder uncontrolled hostility/excitement (Uncon. Hos/Exc) subscale and Marder anxiety/depression (Anx/Dep) subscale, each consists of 4 items with total score equal to sum of 4 items each ranging from 4-28. Higher subscale score indicates greater severity. | Baseline, Week 4 | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Derived Brief Psychiatric Rating Scale (BPRS) Core Score at Week 4 | PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. PANSS derived BPRS is an 18-item clinician rated scale which assesses symptoms such as hostility, suspiciousness, hallucinations, grandiosity, and a number of other psychiatric symptoms. Items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. BPRS core score consists of 4 items (Conceptual disorganization, Hallucinatory behavior, Suspiciousness/persecution, Unusual thought content) with total score equal to sum of the 4 items, ranging from 4 to 28, with higher score indicating greater severity. | Baseline, Week 4 | 
| Clinical Global Impression - Improvement (CGI-I) Score | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Clinician responded to a question: Compared to your subject's condition at the beginning of treatment, how much has your subject changed? Compared to Baseline (Day 1), improvement was defined as score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. | Week 4 | 
| Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 4 | GAF is a 100-point, clinician rated single item scale that rates the severity of illness-related impairment in psychological, social and occupational functioning of participants on a hypothetical continuum of mental illness to mental health. The scale values range from 1 to 100 with lower score indicating greater severity of illness and is divided into 10 equal intervals (descriptors): from 1-10 (persistent danger of hurting self - serious suicidal acting with clear expectations of death) to 91-100 (superior functioning - no symptoms). Each descriptor has a nine-point range to allow for some variability of severity within the descriptor. | Baseline, Week 4 | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) Score | TSQM assesses the participant's level of satisfaction with study medication. It consists of a 14-item questionnaire which comprises of 3 specific scales (effectiveness, side effects, convenience) and 1 global satisfaction scale. Effectiveness, convenience and global satisfaction scale are rated on a 7-point scale (0= Extremely Dissatisfied, 1= Very Dissatisfied, 2= Dissatisfied, 3= Somewhat Satisfied, 4= Satisfied, 5= Very Satisfied, 6= Extremely Satisfied) and side effects are rated on a 5-point scale (0= Extremely Dissatisfied, 1=Very Dissatisfied, 2= Somewhat Dissatisfied, 3= Slightly Dissatisfied, 4= Not at all Dissatisfied). Scale scores are transformed into scores ranging from 0 to 100, with a higher score indicating more satisfaction. | Week 4 | 
| Change From Baseline in Body Weight at Week 4 |  | Baseline, Week 4 | 
| Change From Baseline in Abdominal Girth at Week 4 |  | Baseline, Week 4 | 
| Number of Participants With Clinically Significant Findings in Vital Signs and Electrocardiogram (ECG) | Clinically significant findings based on investigator's discretion were assessed in vital sign parameters (including pulse rate, blood pressure and body temperature) and ECG parameters (including respiratory rate, heart rate, PR interval, QRS interval, QT interval, QT corrected using Bazett's correction [QTcB] interval, and QT corrected using Fridericia's correction [QTcF]). | Baseline up to end of study (7 to 10 days after administration of last dose of study medication) | 
| Number of Participants With Clinically Significant Changes in Physical Examinations | Clinically significant findings in physical examinations based on investigator's discretion were assessed. Screening was the 7 day time (from Day -8 to Day -2) before dosing on Day 1. Number of participants with clinically significant changes in physical examinations compared to screening was assessed. | Screening, Week 4 | 
| Number of Participants With Laboratory Test Abnormalities | Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count: less than(<) 0.8*lower limit of normal (LLN); mean corpuscular volume; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration: <0.9*LLN,>1.1*upper limit of normal (ULN); platelets: <0.5*LLN,>1.75*ULN, white blood cell count: <0.6*LLN, >1.5*ULN; lymphocytes, total neutrophils: <0.8*LLN, >1.2*ULN; eosinophils, basophils, monocytes: >1.2*ULN; coagulation: activated partial thromboplastin time, prothrombin, prothrombin international ratio: >1.1*ULN; liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN; renal function:blood urea nitrogen,creatinine: >1.3*ULN; uric acid: >1.2*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: <0.9*LLN,>1.1*ULN; urinalysis: pH<4.5, >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: <0.6*LLN,>1.5*ULN) | Screening up to end of study (7 to 10 days after administration of last dose of study medication) | 
| Number of Participants With Abnormal White Blood Cell (WBC) Count and Absolute Neutrophil Count (ANC) | Pre-defined criteria was established for WBC Count (less than 0.6 times the lower limit of normal) and absolute neutrophil count (less than 0.8 times the lower limit of normal) to define the values that would be identified as abnormal. | Day 1 up to Week 4 | 
| Number of Participants With Clinically Significant Laboratory Test Abnormalities for Fasting Insulin, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol, Triglycerides, Hemoglobin Type A1c (HbA1c) and Prolactin | Clinically significant findings based on investigator's discretion were assessed in laboratory parameters (including fasting insulin, high-density lipoprotein [HDL], low-density lipoprotein [LDL], Cholesterol, Triglycerides, glycosylated hemoglobin type A1c [HbA1c] and Prolactin). | Day 1 up to Week 4 | 
| Change From Baseline in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Parameter Scores at Week 4 | ESRS-A is a clinician rated scale consisting of 24 items to assess severity of extra-pyramidal symptoms for following parameters: parkinsonism (10 items), dystonia (6 items), dyskinesia (6 items) and akathisia (2 items). Each item is scored on a 6-point Likert scale (0=absent, 1=minimal, 2=mild, 3=moderate, 4=severe, 5=extreme). Total score for a parameter is average of individual item scores included under the parameter, ranging from 0 to 5, with higher score = more affected. | Baseline, Week 4 | 
| Change From Baseline in Movement Disorder Burden Score for Dystonia (MDBS-D) at Week 4 | MDBS-D score reflects the numbers and durations of movement disorder adverse events for dystonia, the severity of the events, required treatment, and the total number of days the participant received study treatment. MDBS-D score = (S * D * C)/TTD; where S= Movement Disorder Severity Score for Dystonia (possible values: 1 [mild]; 2 [moderate]; 3 [severe]), D=adverse event duration (in days), C=concomitant medication factor (C=1.5 if an anti-cholinergic or beta blocker is used for the treatment of a movement disorder; C=1 if no concomitant medication is used), TTD=total treatment days for the participant. Value for MDBS score may range from zero to infinity. A higher MDBS-D score indicates a greater movement disorder adverse event liability compared to baseline. | Baseline, Week 4 | 
| Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) | Data relevant to the assessment of suicidality is mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) event codes. C-SSRS assesses whether participant experiences following: suicide attempt (Event code 2) (Response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (Event code 3) (Yes on aborted attempt, interrupted attempt, preparatory acts or behavior), suicidal ideation (Event code 4) (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) (Yes on Has participant engaged in non-suicidal self-injurious behavior). Number of participants with Yes response for above mentioned categories are assessed. Baseline is defined as the Week 0 measurement. | Baseline, Week 1, 2, 3, 4, Follow-up (FU) (7 to 10 days after administration of last dose of study medication) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, acute exacerbation, inpatient