A study to compare the saftey and efficacy of masitinib to placebo in the treatment of mood disorders in patients with antidepressant-resistant major depression or patients with dysthymic disorder

• Register: EUCTR
• Last refreshed on: 28 May 2018
• Main ID: EUCTR2010-022744-21-ES
• Date of registration: 06/03/2013
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A study to compare the saftey and efficacy of masitinib to placebo in the treatment of mood disorders in patients with antidepressant-resistant major depression or patients with dysthymic disorder
• Scientific title: A 12-week, proof of concept prospective, randomized, double blind, phase 2a study to compare safety and efficacy of masitinib to placebo in the treatment of mood disorders in patients with antidepressant-resistant major depression or patients with dysthymic disorder
• Date of first enrolment: 05/06/2013
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022744-21
• 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

Spain

Contacts

• Name: CEO
• Affiliation: AB Science

• Name: CEO
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with a dysthymic disorder
? According to DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Test Revision) (at least 2 years of depressed mood ?more days than not? and at least 2 of the 6 symptoms items in Criterion B (poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decision, feelings of hopelessness)
? And a baseline score ?12 points on the MADRS scale
? And a baseline score ?17 points on the Hamilton Depression Scale (HAMD-17)
Or patient with a diagnosis of index episode major depression
? According to DSM-IV-TR
? Confirmed by MINI (Mini International Neuropsychiatric Interview)
? With a moderate to severe episode defined as baseline MADRS score ? 26 and baseline CGI-S score ? 4 and a baseline score ?17 points on the Hamilton Depression Scale (HAMD-17)
2. Therapy resistant patient for the Major Depression Group. Patient is considered therapy resistant when consecutive treatment with 2 drugs, used for an appropriate time period (for ? 6 consecutive weeks) at an adequate dose, fail to produce an acceptable effect (investigator?s opinion) or patient presenting with dysthymic disorder who have been unsuccessfully treated with drug based therapy or are considered for drug based therapy
3. Patient with adequate organ function:
- Absolute neutrophils count (ANC) ? 2.0 x 109/L
- Haemoglobin ? 10 g/dL
- Platelets (PTL) ? 100 x 109/L
- AST/ALT ? 2.5x ULN
- Bilirubin ? 1.5x ULN
- Creatinine clearance ? 50 mL/min (Cockcroft and Gault formula)
- Albuminaemia > 1 x LLN
- Urea ? 1.5 x ULN
- Proteinuria < 30 mg/dL on the dipstick; in case of proteinuria ? 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
- Normal TSH concentration. Patient previously diagnosed with hyperthyroidism or hypothyroidism who have been treated with a stable dose of thyroid supplement for at least the past 6 months, have normal TSH concentration, and are euthyroidic are allowed to participate.
4. Male or female patient, aged 18 years and older, with weight > 40 kg or BMI > 18
5. Man or woman of childbearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) who agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.
6. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedure
7. Patient affiliated to a social security system
8. 7. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Patient with psychiatric disorders, including personality disorders, other than major depression or dysthymic disorder
2. Patient with a major surgery within 2 weeks prior to study entry
3. Patient with morbid obesity with BMI > 40
4. Patient with history of suicide attempt within the last 12 months
5. Patient with serious risk for suicide attempt at screening, baseline or during the course of the study as evidenced by a score ? 3 on the Hamilton Depressing Rating Scale suicide item
6. Patient presenting with cardiac disorders defined by at least one of the following conditions:
? Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
? Patient with cardiac failure class III or IV of the NYHA classification
? Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
? Syncope without known aetiology within 3 months
? Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
7. Patient presenting with one of the following conditions:
- Life expectancy < 6 months
- History of primary malignancy < 5 years, except treated basal cell skin cancer or cervical carcinoma in situ
- Patient with any severe and/or uncontrolled medical condition
- Patient with a known diagnosis of human immunodeficiency virus (HIV) infection, of hepatitis C virus infection, of hepatitis B virus infection and of active tuberculosis
8. Patient with chronic diarrhoea, oedema, dermatologic diseases (eczema, psoriasis ?) or history of cutaneous allergy
9. Patient with history of poor compliance or history of drug/alcohol abuse, or current drug/alcohol abuse that might interfere with the ability to comply with the study protocol or give informed consent
10. Patient who have begun a course of psychotherapy within 3 months prior to study entry, or who plan to complete an ongoing psychotherapy prior to the end of the study
11. Patient treated with any psychotropic medication (antipsychotics, antidepressants, mood stabilizers, and stimulants) except if treatment was stopped 4 weeks minimum prior to baseline (6 weeks for fluoxetine). Similarly, patient who has received an investigational drug except if treatment was stopped 4 weeks minimum prior to baseline
12. Patient treated with anxiolytics or hypnotics, except if treatment was stopped more than 4 weeks prior to baseline or if treatment has been taken at a stable dose for 2 months minimum for anxiolytics and 1 month minimum for hypnotic
13. Absence of depressive episode immediately before or during the dysthymic disorder


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

Health Condition(s) or Problem(s) studied

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

mood disorders associated to major depression or dysthymic disorder
MedDRA version: 16.0 Level: PT Classification code 10013982 Term: Dysthymic disorder System Organ Class: 10037175 - Psychiatric disorders
MedDRA version: 16.0 Level: PT Classification code 10012374 Term: Depressed mood System Organ Class: 10037175 - Psychiatric disorders

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Response rate, defined as the proportion of patients with response.
Response is defined as:
- 50% improvement in 17-item Hamilton Depression Scale (HAMD-17)
- and a maximum value of 14 (corresponding to mild depression) on the HAMD-17
- And Clinical Global Impression-Improvement scale (CGI-I) rating of 1 (?very much improved) or 2 (?much improved?)

Secondary Objective: ? Proportion of responders at w4, w8.
? HAMD-17 score every week until w4 and then every 2W until w12
? Proportion of resmission at w4, w8 and w12.
Remission is defined as:
- 50% improvement in 17-item Hamilton Depression Scale (HAMD-17)
- And a maximum value of 7 (corresponding to no depression) on the HAMD-17
- And Clinical Global Impression-Improvement scale (CGI-I) rating of 1 (?very much improved) or 2 (?much improved?)
? Montgomery-Asberg Depression Rating Scale (MADRS) score at w4, w8, w12
? Clinical Global Impression-Improvement scale (CGI-I) score every 1W until w4 and then every 2W until w12
? Clinical Global Impression-Severity scale (CGI-S) score every 1W until w4 and then every 2W until w12
? Leeds Evaluation Sleeping Questionnaire (LESQ) score at w4, w8, w12
? Beck Depression Inventory (BDI) score at w4, w8, w12
? Columbia-Suicide Severity Rating Scale (C-SSRS) score every 1W until w4 and then every 2W until w12

Main Objective: The objective is to compare the safety and efficacy of masitinib 4.5 mg/kg/day to placebo in the treatment of two different patterns of mood disorders: antidepressant resistant major depression and dysthymic disorder.
Efficacy is evaluated using the proportion of responders at week 12.
Response is defined as:
- 50% improvement in 17-item Hamilton Depression Scale (HAMD-17)
- And a maximum value of 17 (corresponding to mild depression) on the HAMD-17
- And Clinical Global Impression-Improvement scale (CGI-I) rating of 1 (?very much improved) or 2 (?much improved?)

Safety is assessed through monitoring of adverse events

Timepoint(s) of evaluation of this end point: week 12

Secondary Outcome(s)

Secondary end point(s): ? Proportion of resmission.
Absolute and relative change from baseline to timepoint for the following variables:
- 17-item Hamilton Depression Rating Scale (HAMD-17) score: HAMD-17 is a 17-items test measuring the severity of depression. The score from each item contribute to a total score. HAMD-17 score increases with depression severity.
- Montgomery-Asberg Depression Rating Scale (MADRS) score: MADRS is a 10-items scale measuring the depression severity. Each item (symptom) is graded on a scale from 0 to 6 and all the items contribute to a total score. MADRS score increases with depression severity.
- Clinical Global Impression-Improvement scale (CGI-I) score: the CGI-I is a 7 point scale to assess how much the patient's illness has improved or worsened compared to a baseline state (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse).
- Clinical Global Impression-Severity scale (CGI-S) score: the CGI-S is a 7-point scale rating the patient's illness based on the clinical experience (1= normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill).
- Leeds Evaluation Sleeping Questionnaire (LESQ): the LESQ is a standardized self-reporting instrument comprising ten items.
- Beck Depression Inventory (BDI) total score: the BDI is a 21-item self-administered questionnaire intended to assess the existence and severity of symptoms of depression. Each item (symptom) is scored from 0 to 3 and all the items contribute to a total score. BDI score increases with depression severity.
- Columbia - Suicide Severity Rating Scale (C-SSRS) score: C-SSRS is a 16-items scale measuring the suicide severity.

Timepoint(s) of evaluation of this end point: week 12

Secondary ID(s)

AB08003

Source(s) of Monetary Support

AB Science