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

• Register: EUCTR
• Last refreshed on: 3 December 2012
• Main ID: EUCTR2010-020764-38-DE
• Date of registration: 11/10/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017, US
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 14/12/2010
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020764-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Males or females aged 18-65 years of age (inclusive) are eligible.
2. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4. Body Mass Index (BMI) of approximately 18 to 40 kg/m2; and a total body weight
>50 kg (110 lbs).
5. Subjects with a diagnosis of schizophrenia must meet the following eligibility criteria in order to be considered for participation in the study. All psychiatric diagnoses specified in the inclusion/exclusion criteria are according to the DSM-IV TR criteria. The subjects are to be assessed by a qualified psychiatrist. The Mini International Neuropsychiatric Interview (M.I.N.I.) will be used to confirm diagnosis and exclude comorbid diagnoses:
• Subjects must have a total BPRS score of =45 at the screen visit.
• Subjects must have a score of =4 (moderate) on at least 2 items of the 4 BPRS core psychosis items (ie, #4 conceptual disorganization, #11 hallucinatory behavior, #12 suspiciousness, #15 unusual thought content) at screening and baseline.
• Subjects must have a total score of at least 12 on the combination of the 4 BPRS core psychosis items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) at screening and baseline.
• Subjects must have a Clinical Global Impression of Severity (CGI-S) scale score of
=4 (moderately ill) at the screen and baseline visit.
6. Subjects must have a known change in their level of functioning associated with their current acute exacerbation of schizophrenia (eg, ER admission, change in level of supervision, worsening of symptoms) as noted/documented by the treating psychiatrist, family member or caregiver, or other clinical information source.
7. The current acute exacerbation of schizophrenia must be less than 4 weeks duration prior to the screen date. Narrative information must be recorded in the screening worksheets documenting the acuteness of current episode, history of exacerbations, and levels of response to past treatments.
8. If subjects are hospitalized for acute exacerbation of schizophrenia at the time of screening, the duration of the current hospitalization must be less than 2 weeks prior to the screen date.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study (the list of exclusion criteria is abridged - a full list of exclusion criteria can be found within the protocol):
1. Subjects who have a greater than a 25% decrease in the BPRS core psychosis items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) total score between screening and baseline.
2. Female subjects who are pregnant or breastfeeding: Female subjects of childbearing potential may be included in the study but must be sexually abstinent or must agree to practice established effective contraception from the screening evaluation until 30 days following the last dose of the study drug. Investigators should specifically question female subjects regarding potential unprotected sexual activity in the 14 days prior to screening to assess risk for pregnancy.
3. Subjects with evidence or history of clinically significant hematological, renal, endocrine (excluding adequately controlled hypothyroidism or hyperthyroidism), pulmonary (excluding chronic bronchitis, mild emphysema or chronic obstructive pulmonary disease), gastrointestinal (including conditions that can affect drug absorption, eg, gastrectomy), oncological, dermatologic, immunologic disease, as determined by the investigator. Controlled Type 2 diabetes (glucose <180 mg/100 mL at screening with dietary or oral hypoglycemic treatment) will not be considered a significant medical illness and would not exclude a subject from the study.
4. Subject with evidence or history of significant hepatic disorder, including acute or chronic hepatitis B and acute hepatitis C, with liver function test results higher than the normal limits. Subjects with positive hepatitis C antibody and normal liver functions tests can be included in the study.
5. Subjects who are known to have AIDS or to be HIV positive.
6. Subjects with evidence or history of clinically significant cardiovascular disease, including uncontrolled hypertension (sitting or supine diastolic pressure >95 mm Hg and/or sitting or supine systolic pressure >170 mm Hg with or without treatment), bypass surgery, history of myocardial infarction or ischemic heart disease, uncompensated heart failure or recent acute myocardial infarction. Controlled essential hypertension and non clinically significant sinus bradycardia and sinus tachycardia will not be considered significant medical illnesses and would not exclude a subject from the study.
7. Subjects with a 12-lead ECG with repeated demonstration of QTcF >450 msec at screening or at baseline (Day 1) based on the machine reading.
8. Subjects with a WBC<3500/mm3 and ANC <2000/mm3, or WBC <3000/mm3 and an ANC <1500/mm3 in subjects with a documented history of benign ethnic neutropenia.
9. Subjects with a history of myeloproliferative disorder or clozapine induced agranulocytosis or granulocytopenia.
10. Subjects with screening laboratory test results that deviate from the upper or lower limits of the reference range, except for not clinically significant values, as determined by the investigator. AST or ALT must be =2 X upper limit of reference range, and total bilirubin must be within 1.5 X of the upper limit of reference range at screening.
11. Subjects who have a positive urine drug screen which cannot be explained by prescribed medications.
12. Subjects who are using prohibited medications (as described in Section 5.5 and Appendix 1 of the protocol) and who wil

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Schizophrenia
MedDRA version: 12.1 Level: LLT Classification code 10009134 Term: Chronic schizophrenia

Intervention(s)

Product Name: PF-02545920
Product Code: PF-02545920
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-02545920
Other descriptive name: 2-[[4-[1-Methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy]methyl]quinoline butanedioic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Risperdal®
Pharmaceutical Form: Capsule*
CAS Number: 106266-06-2
Other descriptive name: RISPERIDONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Risperdal®
Pharmaceutical Form: Capsule*
CAS Number: 106266-06-2
Other descriptive name: RISPERIDONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the efficacy of PF-02545920 in the treatment of acute exacerbation of schizophrenia using the:
•Clinical Global Impression of Improvement (CGI-I) and Clinical Global Impression of Severity (CGI-S);
•PANSS Subscales: Positive, Negative, General;
•PANSS derived Marder factor scores1 (positive, negative, disorganized thought, hostility/excitement, anxiety/depression);
•PANSS derived Brief Psychiatric Rating Scale (BPRS) core psychosis items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content);
•Global Assessment of Function (GAF);
•Treatment Satisfaction Questionnaire for Medication (TSQM).
Other secondary objectives:
•Collection of de-identified molecular profiling blood samples to support qualification of exploratory biomarkers and pharmacogenomic endpoints for use in future studies of PF-02545920 and other novel neuroscience therapeutic compounds.

Primary end point(s): Primary efficacy:
• PANSS Total change from baseline.
Primary Safety:
• Dystonia incidence rate.
Pharmacokinetics:
•Sparse PK sampling for population PK analysis.

Main Objective: •To evaluate the efficacy of PF-02545920 in the treatment of acute exacerbation of schizophrenia during a 4-week double-blind treatment period using the Positive and Negative Syndrome Scale (PANSS) to measure change in symptoms from baseline compared to placebo.
•To evaluate the safety and tolerability of two fixed dose regimens of PF-02545920 in the treatment of acute exacerbation of schizophrenia.
•To evaluate the incidence rate of dystonia associated with two doses of PF-02545920 compared to placebo in the treatment of acute schizophrenia.

Secondary ID(s)

A8241012