A dose-finding study of efficacy and safety of F13640 in patients with moderate to severe painful peripheral diabetic polyneuropathy - BEST- Diabetes study (Befiradol Dose-Finding Study in diabetic patients)

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2009-012123-28-DE
• Date of registration: 29/07/2009
• Prospective Registration: Yes
• Primary sponsor: Institut de Recherche Pierre Fabre
• Public title: A dose-finding study of efficacy and safety of F13640 in patients with moderate to severe painful peripheral diabetic polyneuropathy - BEST- Diabetes study (Befiradol Dose-Finding Study in diabetic patients)
• Scientific title: A dose-finding study of efficacy and safety of F13640 in patients with moderate to severe painful peripheral diabetic polyneuropathy - BEST- Diabetes study (Befiradol Dose-Finding Study in diabetic patients)
• Date of first enrolment: 09/12/2009
• Target sample size: 550
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012123-28
• 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

Countries of recruitment

Bulgaria, Czech Republic, France, Germany, Hungary, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
- Outpatient, man or woman, 18 to 65 years old
- Woman of child-bearing potential must have been using an effective method of contraception (defined as chirurgical or hormonal birth control, or intra-uterine device only), assessed by the investigator, for at least 2 months before the selection in the study, and must accept to go on using it during the whole duration of the study and up to 1 month after the last dose of the study treatment, in order to avoid pregnancy while being exposed to the study treatment. A pregnancy test will be carried out at selection visit, at randomisation visit and at the last study visit of the
patient.
- Moderate to severe painful peripheral diabetic polyneuropathy with the 4 following characteristics: Diagnosis based on clinical examination, and appropriate assessment of patient’s signs and symptoms (clinical portion of Michigan Neuropathy Screening Instrument score = 3)
Following diabetes mellitus type 1 or 2, diagnosed for at least 3 years with stable glycaemic assessment for at least 3 months
Haemoglobin A1c (HbA1c) level <10 % at selection
Pain persisting for more than 3 months
- Average 24-hour recall pain intensity score > 40 and < 90 on a 0-100 Visual Analogue Scale (VAS) at selection visit
- Average 24-hour recall pain intensity score in the PED > 40 on a 0-100 unit VAS, over the week preceding randomisation visit (at least 4 assessable days)

-Affiliated to a social security system, or is a beneficiary, if applicable in the national regulation
-Patient having signed his/her written informed consent
-Patient able and willing to use the PED device daily for the duration of the study; able to hear and respond to the PED audible prompts, able to read and understand the text in local language on the PED
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:
- Any clinically significant hepatic, renal, gastro-intestinal, endocrinal (excluding diabetes mellitus), cardiovascular, neurological, psychiatric or haematological or current disease unrelated to the cause of pain, which may interfere with pain evaluation, patient safety and the course of the study in the investigator’s opinion
- Current major depressive disorder requiring a pharmacological treatment
- Severe nephropathy (creatinine clearance < 50 ml/min, MDRD formula)
- Presence of significant nociceptive, inflammatory or central neuropathic pain
- Presence of vascular chronic pain, with particular regard for severe diabetic arteriopathy of the lower limbs characterised by the presence of ulceration and/or necrosis
- Phantom pain
- Complex Regional Pain Syndrome
- Physical techniques, surgery and psychological support that can modulate the perception of pain (except if maintained stable during the trial when unavoidable
- AST/SGOT and ALT/SGPT greater than 2 time the upper normal values
- Blood creatinine value > 150 µmol/L
- Albuminuria/creatininuria ratio > 300 mg/g
- SBP < 120 mm Hg (at selection and randomisation, in supine position, and after a 10 min-rest)
- ECG: QTc > 450 ms
- History of alcohol or narcotic drug dependence in the 2 years preceding the selection or alcohol or narcotic abuse in the 6 months preceding the selection
- Known hyper-reactivity or hyper-sensitivity to 5-HT agonists
- Intake of any prohibited treatments which cannot be stopped
- For patient having been treated by prohibited treatments, no respect of a wash-out period of at least 5 T1/2 of the treatment prior to randomisation
- Woman pregnant or in the post-partum period (at least 6 months) or is a nursing mother
- Woman sterile or in post-menopause state (12 month-amenorrhoea) impossible to document
- Is a family member or work associate (secretary, nurse, technician,…) of the Investigator
- Mentally unable to understand the nature, objectives and possible consequences of the trial; or refusing to subject himself / herself to its constraints
- Has participated in another clinical trial within the last 3 month(s), has received treatment with known remanant effects or undergone investigation liable to interfere with the present clinical trial
- Has forfeited his / her freedom by administrative or legal award or is under guardianship


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

Health Condition(s) or Problem(s) studied

Diabetic peripheral neuropathy
MedDRA version: 9.1 Level: LLT Classification code 10012683 Term:

Intervention(s)

Product Name: Befiradol
Product Code: F13640
Pharmaceutical Form: Tablet
INN or Proposed INN: Befiradol
CAS Number: 208110-64-9
Current Sponsor code: F13640
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Befiradol
Product Code: F13640
Pharmaceutical Form: Tablet
INN or Proposed INN: Befiradol
CAS Number: 208110-64-9
Current Sponsor code: F13640
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The first study objective is to define the dose-response relationship of F13640 compared to a placebo with respect to analgesic efficacy and safety in patients with moderate to severe painful peripheral diabetic polyneuropathy.

Primary end point(s): Response to treatment defined as a decrease of at least 30% on the weekly average 24-hour recall pain intensity score on a 0-100 Visual Analogue Scale (VAS), between the baseline (the last week before the first study drug intake, scheduled on D1) and the last week before the end of fixed dose period (D56 or End of Fixed Dose visit –EFD-). Patients who discontinued prematurely fixed dose for insufficient response and/or worsening will be classified as non-responders. For patients having taken rescue medication and for patients who take non-allowed concomitant treatment during the last week before the end of fixed dose period, Validation Committee will decide whether he (she) is a responder or not.

Secondary Objective: The second objectives are the evaluation of potential rebound effect, addiction effect and remanent dose effect after study treatment discontinuation.

Secondary ID(s)

2009-012123-28-FR

F13640 CP 201