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

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ClinicalTrials.gov Identifier: NCT02522104
Recruitment Status : Completed
First Posted : August 13, 2015
Last Update Posted : January 24, 2017
Sponsor:
Information provided by (Responsible Party):
ADDMEDICA SASA

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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Renal Function Disorder Drug: Siklos Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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)
Actual Study Start Date : September 3, 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 28, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests
Drug Information available for: Hydroxyurea

Arm Intervention/treatment
Experimental: Normal-renal function
Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Drug: Siklos
Other Name: hydroxyurea

Experimental: Glomerular hyperfiltration
Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Drug: Siklos
Other Name: hydroxyurea

Experimental: Moderate renal failure
Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2
Drug: Siklos
Other Name: hydroxyurea




Primary Outcome Measures :
  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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02522104


Locations
France
Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
Creteil, France
Sponsors and Collaborators
ADDMEDICA SASA
Investigators
Principal Investigator: BARTOLUCCI Pablo, MD Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor

Responsible Party: ADDMEDICA SASA
ClinicalTrials.gov Identifier: NCT02522104     History of Changes
Other Study ID Numbers: SIK-FR 14-1
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: January 24, 2017
Last Verified: January 2017

Keywords provided by ADDMEDICA SASA:
Pharmacokinetics of Hydroxyurea

Additional relevant MeSH terms:
Anemia, Sickle Cell
Renal Insufficiency
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Kidney Diseases
Urologic Diseases
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors