Proliferating Infantile Hemangioma MedDRA version: 12.1 Level: LLT Classification code 10018814 Term: Haemangioma
Conditions
Interventions
Product Name: V0400SB07
Product Code: V0400SB07
Pharmaceutical Form: Oral solution
INN or Proposed INN: PROPRANOLOL HYDROCHLORIDE
CAS Nu
Sponsors
PIERRE FABRE DERMATOLOGIE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible if he/she meets all of the following criteria: • Written informed consent(s) for study participation is obtained according to national regulations from the patient’s parent(s) or guardian(s) prior to performing any study procedures, • The patient is 35 to 150 days old, inclusive, at inclusion, • Proliferating IH (target hemangioma) requiring systemic therapy is present: function-threatening IH, IH in certain anatomic locations that often leave permanent scars or deformity, large facial IH, smaller IH in exposed areas, severe ulcerated IH, pedunculated IH, • Affiliated with, or beneficiary of the social security. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no 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
Exclusion criteria: A patient will be ineligible if he/she meets any of the following criteria: • The patient has a medically unstable health status that may interfere with his/her ability to complete the study, • The patient presents with one or more of the following medical conditions: Congenital hemangioma; Kasabach-Merritt syndrome; bronchial asthma; bronchospasm; hypoglycaemia (< 40 mg/dl or at risk); untreated phaeochromocytoma; hypotension (< 50/30); second or third degree heart block; cardiogenic shock; metabolic acidosis; bradycardia (< 80 bpm); severe peripheral arterial circulatory disturbances; Raynaud’s phenomenon; sick sinus syndrome; uncontrolled heart failure or Prinzmetal’s angina; documented PHACES syndrome with central nervous system involvement, • The patient (and/or the mother if she is breastfeeding the patient) has received at least one of the following prohibited medications within 15 days of randomisation: o Anaesthetic agents (the exclusion period is shortened to 48 hours, if anaesthesia has been performed for diagnosis investigation (e.g. MRI…) o Cardiovascular treatments: anti-arrhythmics, calcium channel blockers, ACE inhibitors, inotropic agents, vasodilators (hydralazine hydrochloride…), clonidine… o Hypoglycaemic agents or drugs able to induce hypoglycaemia o Anti-ulcer drugs (cimetidine…) o Metoclopramide o Prostaglandin synthetase inhibitors o Sympathomimetic agents and parenteral adrenaline o Benzodiazepines o Neuroleptic drugs (chlorpromazine, sultopride hydrochloride…) o Other drugs: triptans, ergotamine, theophylline, warfarin, thyroxine, floctafenine, • The patient (and/or the mother if she is breastfeeding the patient) has received any treatment which could lead to induction or inhibition of hepatic microsomal enzymes within 2 months of randomisation, • The patient has previously been administered at least one of the following prohibited medications: systemic (oral, intra-venous or intra-muscular), intra-lesional or topical corticosteroids, imiquimod, vincristine, alfa-interferon, Propranolol or other beta-blockers, • The patient has previously been treated for IH, including any surgical and/or medical procedures (e.g. laser therapy), • The patient’s mother has been breastfeeding the patient while she was also being treated with beta-blockers (including Propranolol ) or, she has been breastfeeding the patient within 15 days of randomisation while she was also being treated with systemic (oral, intra-venous or intra-muscular) corticosteroids, vincristine or alfa-interferon, • The patient is known to have a hypersensitivity to Propranolol or to any component of the investigational product and/or any other beta-blockers, • The patient has previously experienced an anaphylactic reaction, • The patient has a life-threatening IH, • Diagnosis of the soft tissue tumour as IH is not clinically certain, particularly in the case of sub-dermal lesions, • The patient was born prematurely and has not yet reached his/her term equivalent age (e.g. an infant born 2 months prematurely cannot be included before the age of 2 months), • LVEF (left ventricular
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to characterise the pharmacokinetics of Propranolol at steady-state in infants during a treatment for proliferating infantile hemangiomas requiring systemic therapy.; Secondary Objective: • To assess efficacy of Propranolol on the evolution of the target IH over 12 weeks. • To document the safety profile of Propranolol in the treatment of IH ; Primary end point(s): Primary criterion: Pharmacokinetics The pharmacokinetic assessment will primarily evaluate at steady-state, the rate and extent of absorption, as well as the total plasma clearance of Propranolol in infants. According to their stratification group, pharmacokinetic sampling will be performed at 1 month or 3 months after the beginning of treatment. During the titration period, 2 micro-blood samples for Propranolol plasma level determination will be obtained at D7 and D14, respectively through puncture of a peripheral vein in the forearm after an appropriate local anaesthetic application. At steady-state, micro-blood samples for Propranolol plasma level determination will be drawn via a catheter after an appropriate local anaesthetic application. Six (6) micro-blood samples will be collected over a 9 hour-period: T0 (just before morning dosing, 12 hours after the previous evening administration) and 1h, 2h, 4h, 6h and 9h after the morning administration. Blood samples will be centrifuged; plasma will be separated and frozen at – 20°C until assay. Bioanalysis: Propranolol plasma concentrations will be quantified using a validated LC/MS-MS method The following pharmacokinetic parameters will be assessed for propranolol using a non-compartmental approach: Cmax, Tmax, AUCt and Cl/F. | — |
Countries
France
Outcome results
None listed