Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)

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Status and phase: Completed; Phase 4

Conditions: Sickle Cell Disease; Renal Function Disorder

Treatments: Drug: Siklos

Study type: Interventional

Funder types: Industry

Identifiers

NCT02522104

SIK-FR 14-1

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 3 patient groups

Normal-renal function

Experimental group

Description:

Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men

Treatment:

Drug: Siklos

Glomerular hyperfiltration

Experimental group

Description:

Glomerular renal hyperfiltration: GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.

Treatment:

Drug: Siklos

Moderate renal failure

Experimental group

Description:

Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2

Treatment:

Drug: Siklos