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NCT Number: NCT02522104

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

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Renal Function Disorder

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor

Créteil, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Siklos

Drug

Other names: hydroxyurea

Primary outcomes

  1. Measure of Plasmatic Data: Maximum Concentration (Cmax)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  2. Measure of Plasmatic Data: Minimum Concentration (Cmin)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  3. Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  4. Measure of Plasmatic Data: Area Under the Curve (AUC0-24)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  5. Measure of Plasmatic Data: Elimination Half-life (T½)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  6. Measure of Plasmatic Data: Total Clearance (Cl Tot)

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  7. Measure of Plasmatic Data: Distribution Volume

    Time frame: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  8. Measure of Urinary Data: Hydroxyurea Urinary Fractions

    Time frame: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

  9. Measure of Urinary Data: Renal Clearance (Cl Renal).

    Time frame: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours

    Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

Sponsors and collaborators

Lead sponsor

Theravia

Industry

Registry information

Official study 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)

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Aug 13, 2015
Registry last updated
Oct 12, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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