Siklos is indicated for the prevention of recurrent painful vaso-occlusive crises including acute chest syndrome in adults, adolescents and children older than 2 years suffering from symptomatic sickle cell syndrome. MedDRA version: 17.1 Level: LLT Classification code 10040643 Term: Sickle cell crisis System Organ Class: 100000004851
Conditions
Interventions
Trade Name: SIKLOS
Product Name: Siklos
Pharmaceutical Form: Film-coated tablet
Sponsors
Addmedica S.A.S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Age = 18 years. b. Masculin or feminin sex. c. Drepanocytose (SS or S-ß0thal) confirmed by hemoglobine electrophorese and genotype of desosxyribonucleic acid (DNA). d. adhere to national insurance program. e. Have given their free consent after having been informed of the goals, proceedings, and potential risks . these criteria will be applied to all 3 groups. The group the subjects will belong to will be defined by the glomerular filtration rate (GFR) estimated using Chronic Kidney Disease EPIdemiology (CKD EPI) cformular without etnic criteria. Underhydroxyurea (Siklos®) treatment .with stable psology for at least 1 week± 2 jours before inclusion and taken every morning at 9h ± 15 minutes. 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 42 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a. Consent refusal b. Non observant patient. c. Having suffered from a vaso-occlusive crisis during the month before inclusion. d. having undergone tranfusional exchange withiin the 3 months prio to inclusion. e. Patients participating to anothe study or in exclusion period from a previous study. f. Patients under diuretics. g. Patients suffering from an intercurrent illness, particularly inflammatory, non resolved since at least 1 month. h. Patiente pregnat or breast-feeding. i. Patients with no or restraint freedom. j. Patients unable to understand the goal of the study therefore not able to give their consent. k. if suffering from severe hepatic failure. l. in case of severe hepatic failure (creatinine clairance < 30 mL/min). m.Patients presenting toxic signs of myelosuppression.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of the different pharmacokynetics parameters of hydroxyurea in sickle-cell patients with a renal condition (glomerular hyperfiltration and moderate renal) to those presenting a normal renal function.;Secondary Objective: a. Development of a pharmacokinetic model to measure the variability of pharmacokinetic parameters in the study population. b. Definition of the relevant covariates: demographic, biologic, therapeutic (treatment with angiotensin-converting-enzyme inhibitors) explaining the pharmacokinetic variability of hydroxyurea for each study group. c. Definition of a model including the individual pharmacokinetic parameters allowing to adapt the posology of hydroxyurea according to the renal function.;Primary end point(s): comparison of the below pharmacokynetics parametres amongst the 3 studied groups (3 different renal conditions) with a P value <0.05 : •Plasmatic data: Cmax, Cmin, Tmax, AUCO-24, T1/2, CI tot and distribution volumen. •Urine data: hydroxyurea urine fractions, renal CI.;Timepoint(s) of evaluation of this end point: Biological blood tests: %HbF, hemogram, reticulocytaire formulae, urea, creatinine, ALAT, ASAT, LDH, total bilirubine, akaline reserve at T-1h Hydroxyurea level at T0h Hydroxyurea pharmacokynetic: T0, 0.75h, 1.5h, 3h, 4h, 6h, 7.5h, T24 urine sampling Hydroxyurea pharmacokynetic and diurese: T0-4h, 4-7.5h + T24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a.Pharmacokynetic Model selection criteria: likelihood test and Objective Function minimisation (OF) between the reduced and final model: if ?OF = 3.84 complete model superior to reduced model (P<0.05). b. Covariables selection criteria: likelihood test and Objective Function minimisation (OF) between the reduced and final model: if ?OF = 3.84 complete model superior to reduced model (P<0.05). c. Model validation criteria using Bland and Altman test by evaluatinf the agreement between calculated parametres using the model and the observed ones: data cloud distribution between superior limit agreement [biais+ (standard deviation*1.96)] and inferior limit agreement [biais- (standard deviation*1.96)] d. Pharmacokynetic parametres variations of hydroxyurea in patients treated by Ramipril during 2 periods: period 1: under ramipril period 2: after 30 days wash-out of any ARA II including ramipril;Timepoint(s) of evaluation of this end point: T24h | — |
Countries
France
Contacts
Public ContactMedical director
Addmedica S.A.S
Outcome results
None listed