Effects of F17464 in acute exacerbation of schizophrenia.

• Register: EUCTR
• Last refreshed on: 23 May 2016
• Main ID: EUCTR2013-005451-32-LV
• Date of registration: 13/05/2014
• Prospective Registration: Yes
• Primary sponsor: Pierre Fabre Médicament represented by the Institut de Recherche Pierre Fabre (IRPF)
• Public title: Effects of F17464 in acute exacerbation of schizophrenia.
• Scientific title: Effects of F17464 in acute exacerbation of schizophrenia. - FAST (F17464 in Acute Schizophrenia Trial)
• Date of first enrolment: 28/07/2014
• Target sample size: 142
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005451-32
• 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: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Hungary, Latvia, Russian Federation

Contacts

• Name: Christine PETILAIRE-BELLET
• Affiliation: Institut de Recherche Pierre Fabre

• Name: Christine PETILAIRE-BELLET
• Affiliation: Institut de Recherche Pierre Fabre

Key inclusion & exclusion criteria

Inclusion criteria:
Demographic and other characteristics
1.Male or female, 18-64 years of age inclusive;
2.For female patient of child-bearing potential:
•Must have been using an effective method of contraception (defined as surgical or hormonal birth control, or intra-uterine device only), assessed by the investigator, for at least 2 months before the enrolment in the study (Visit 1), and must accept to go on using it during the whole duration of the study and up to 1 month after the study end visit, in order to avoid pregnancy while being exposed to the study treatment. A pregnancy test will be carried out at enrolment visit (Visit 1), at inclusion visit (Visit 2) and at the End Of Treatment visit of concerned patient;
•Agreement of her male partner(s) to use a condom during each sexual intercourse during the study period and to continue until 1 month after the study end visit;
3.For male patient:
•Agreement to use an effective contraceptive method himself and his female partner(s) during each sexual intercourse during the study period and to continue until 3 months after the study end visit.
Diagnostic criteria
Schizophrenia history: Before Visit 1
4.Patient with a current primary diagnosis of schizophrenia undergoing an acute exacerbation with prominent “active phase“ symptoms, as described by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition – Text Revision (DSM IV-TR) using the MINI 6.0 (Mini-International Neuropsychiatric Interview) for schizophrenia and psychotic disorders related to DSM IV-TR;
5.For a minimum of 1 year and maximum 5 years, well-documented diagnosis with the first hospitalization for acute exacerbation of schizophrenia;
6.Since the diagnosis of schizophrenia, the average number of hospitalisations should be no higher than 2 per year (the minimum duration of hospitalization should be more than 4 days);
7.During the year before Visit 1, maximum 3 acute psychotic episodes that required hospitalization or change of antipsychotic medication or other therapeutic intervention;
8.Adequate clinical response to well-conducted treatment courses during previous acute episodes. A well conducted treatment course is defined as an antipsychotic treatment with the usual doses for at least 4 weeks;
Current acute episode:
9.Structured Clinical Interview for the Positive And Negative Syndrome Scale (SCI-PANSS) with a PANSS total score = 70 to < 120 (at Visit 1 and 2);
10.Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms: delusions, hallucinatory behaviour, conceptual disorganization, suspiciousness/persecution;
11.Clinical Global Impression of Severity (CGI-S) score = 4 (moderate or severe).
12.Antipsychotic initiated for this acute episode and/or ongoing chronic antipsychotic treatment, with a maximum of 2 antipsychotics in total needed to be changed (due to inefficacy or safety reasons) ;
13.Hospitalization and/ or treatment for the current psychotic episode for less than 2 weeks prior to Visit 1;
14.No significant improvement of PANSS total score between enrolment (Visit 1) and inclusion (Visit 2) corresponding to a score improvement < 20% on positive symptoms subscale;

Examination
15.Normal physical examination results, vital signs and clinical laboratory test results or other results judged not clinically significant by the investigator;
16.Body mass index (BMI) = 18 and = 35kg/m2 inclusive.

Ethical/legal considerations
17.Patient able to read and understand the information leaf
Exclusion criteria:
Related to the pathology
1.Patients in their first acute episode of psychosis;
2.Current schizophrenic episode with predominant negative symptoms;
3.Patient « known to be refractory » defined as lack of significant improvement (no significant relief of symptoms, and no period of good function) despite adequate courses with at least 3 different antipsychotics medication cycles of an adequate duration (at least 4 weeks) and at adequate dosage during the previous 5 years;
4.Schizoaffective disorder, schizophreniform disorder and other psychotic disorders;
5.Bipolar I and II disorder;
6.Pervasive developmental disorder, mental retardation, delirium, dementia, memory impairment and other cognitive disorders that would compromise a reliable assessment according to the investigator’s opinion;
7.Known or suspected borderline or antisocial personality disorder or other DSM IV axis II disorder of sufficient severity to interfere with participation in this study;
8.History of tardive dyskinesia or chronic extra-pyramidal symptoms (EPS), serotonin syndrome or neuroleptic malignant syndrome;
9.Major depressive disorder which requires a pharmacological treatment;
10.At imminent risk of injuring him/herself or others or causing significant damage to property, as judged by the investigator;
11.Suicidal risk based on the Columbia-Suicide Severity Rating Scale (C-SSRS):
•Any suicidal behavior in the past year,
•Suicidal ideation of type 4 or 5 in the past month.
Related to treatments
12.Structured psychotherapy (e.g. cognitive behavioural therapy) started within 6 weeks before Visit 1;
13.Electroconvulsive therapy within 3 months before Visit 1;
14.Previous lack of response to electroconvulsive therapy;
15.Treatment ongoing with a depot neuroleptic (even if less than 1 cycle in duration before Visit 1);
16.Patient having previous treatment course with clozapine within 4 months prior to Visit 1;
17.Requirement of concomitant treatment with any of the prohibited medications, supplements, herbal products or products listed in “Prohibited concomitant treatments for associated drug -drug interactions”, including any psychotropic drug or any drug with psychotropic activity or with a potentially psychotropic component;
18.History of intolerance or hypersensitivity to other drugs of the same chemical class as F17464 or to rescue medications or any history of severe drug allergy or hypersensitivity;

Related to medical conditions
19.History or presence of any significant or uncontrolled medical finding such as cancer or neurological, cardiac, hepatic, metabolic, renal, haematological, muscular, endocrine, respiratory, gastrointestinal, dermatological, venereal disorders or diseases, or of any other significant medical condition that may impact the safety, the interpretation of the results, that might affect the absorption, distribution, biotransformation or excretion of the investigational product and/or the participation of the patient in the study according to the opinion of the investigator;
20.History of seizure disorder, stroke, significant head injury, severe chronic movement disorder or psychiatric symptoms possibly secondary to any other organic medical condition;
21.Known human immunodeficiency virus (HIV) or hepatitis B or C infection;
22.Liver enzyme tests (AST, ALT) > 2x upper limit of normal or any abnormal level judged as clinically significant by the investigator;
23.ECG out of normal ranges (45 < or = HR < or = 90 bpm, 120 < or = PR < or = 20

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

Health Condition(s) or Problem(s) studied

schizophrenia
MedDRA version: 17.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Intervention(s)

Product Name: F17464
Product Code: F17464
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not applicable
Current Sponsor code: F17464
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the potential efficacy of 40 mg/day of oral F17464 in comparison to placebo over 6 weeks in patients with acute exacerbation of schizophrenia

Primary end point(s): Primary efficacy parameter
PANSS total score.

Timepoint(s) of evaluation of this end point: All visits

Secondary Objective: •To assess safety of the tested product
•To describe pharmacokinetics of F17464 in this patient population
•To assess the genotype-efficacy relationship

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy parameters
CGI-S and CGI-I
PANSS subscores.

Tolerability and Safety
- Adverse Events (observed and / or spontaneously reported)
- Physical examinations, including body weight, BMI and waist circumference
- Standard 12-lead ECG
- Blood pressure and heart rate
- CDSS (Calgary Depression Scale for Schizophrenia
- EPS scales : BARS, AIMS, SAS
- Suicidal risk scale: C-SSRS (Columbia-Suicide Severity Rating Scale)
- Blood and urine laboratory tests
- Fasting glucose
- Hemoglobin A1c
- Haematology
- Biochemistry
- Serum-hCG pregnancy test
- Urinary pregnancy test

Pharmacodynamics : Prolactin (PRL) (blinded for Sponsor and investigator)

Pharmacokinetics : Plasma concentrations of F17464: 11 blood samples will be collected for each patient.

Genotyping : Genotype regard D3 receptors will be determined on blood sample

Timepoint(s) of evaluation of this end point: Secondary efficacy
CGI-I : Visit 3,4,5,6,7,8,9
CGI-S : Visit 1,2,6,9,10.

Tolerability and safety
Depending on examination.

Pharmacodynamics
Visit 2,4,5,6,9,10.

Pharmacokinetics
Visit 4,5,6,7,8,9.

Genotyping
Visit 2.

Secondary ID(s)

2013-005451-32-HU

F17464GE201

Source(s) of Monetary Support

Institut de Recherche Pierre Fabre