Clinical trial NCT02522104: Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
Official title: Evaluation of the Impact of Renal Function on the Pharmacokinetics of Hydroxyurea (SIKLOS ®) in Normal-renal Function, Hyperfiltrating and Renal Failure Sickle Cell Disease Patients (DARH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sickle Cell Disease
Renal Function Disorder
Keywords: Pharmacokinetics of Hydroxyurea
Lead sponsor: Theravia
Sponsor class: INDUSTRY
First posted: 2015-08-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The use of hydroxyurea in sickle cell disease patients with glomerular hyperfiltration and renal failure requires a specific monitoring and dose adjustment in order to remain within the therapeutic interval while limiting the risk of toxicity or therapeutic failure. For this reason the investigators propose to compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Male or female.
* Sickle cell disease (SS or S-β0thal) confirmed by haemoglobin electrophoresis and genotyping by deoxyribonucleic acid (DNA) analysis.
* Affiliation to a social security system.
* Having freely consented in writing after being informed of the objective, programme and potential risks incurred.

These criteria will apply to the 3 groups of sickle cell disease patients according to the renal function stage defined by the glomerular filtration rate (GFR) estimated by the formula of the Chronic Kidney Disease EPIdemiology (CKD EPI) collaboration without ethnic criterion during the last 6 months before inclusion:

* Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men.
* Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2.
* Glomerular renal hyperfiltration: GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.

  * Treated with hydroxyurea (Siklos®) with a stable dosage for at least one week ± 2 days before inclusion in the study and dose administered in the morning at 9:00 ± 15 minutes.

Exclusion Criteria:

* Refusal to consent.
* Patients that do not comply.
* Occurrence of vaso-occlusive crisis in the month prior to the inclusion in the study.
* Patients having had an exchange transfusion in the 15 days before inclusion in the study.
* Patients participating in another clinical trial or in the exclusion period of a previous clinical trial.
* Patients treated with a diuretic.
* Dialysis patient.
* Patients with an intercurrent disorder, especially inflammatory, that has not recovered for at least one month.
* Pregnant or breast-feeding women.
* Patients deprived of liberty or under legal protection.
* Patients who cannot understand the objective and the course of the study, incapable of giving their consent.
* In the event of severe hepatic failure.
* In the event of severe renal failure (creatinine clearance \< 30 ml/min).
* Patients who show toxic signs of bone marrow suppression.

Primary outcomes:
measure: Measure of Plasmatic Data: Maximum Concentration (Cmax)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Minimum Concentration (Cmin)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Elimination Half-life (T½)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Total Clearance (Cl Tot)
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Plasmatic Data: Distribution Volume
timeFrame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
measure: Measure of Urinary Data: Hydroxyurea Urinary Fractions
timeFrame: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
measure: Measure of Urinary Data: Renal Clearance (Cl Renal).
timeFrame: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Creteil
country: France
facility: Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
Study officials:
affiliation: Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
name: BARTOLUCCI Pablo, MD
role: PRINCIPAL_INVESTIGATOR
References: