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

Primary Purpose

Sickle Cell Disease, Renal Function Disorder

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Siklos
Sponsored by
ADDMEDICA SASA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Sickle Cell Disease focused on measuring Pharmacokinetics of Hydroxyurea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Normal-renal function

Glomerular hyperfiltration

Moderate renal failure

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Measure of Plasmatic Data: Maximum Concentration (Cmax)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Minimum Concentration (Cmin)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Elimination Half-life (T½)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Total Clearance (Cl Tot)
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Distribution Volume
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Urinary Data: Hydroxyurea Urinary Fractions
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Urinary Data: Renal Clearance (Cl Renal).
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure

Secondary Outcome Measures

Full Information

First Posted
August 4, 2015
Last Updated
September 20, 2021
Sponsor
ADDMEDICA SASA
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1. Study Identification

Unique Protocol Identification Number
NCT02522104
Brief Title
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

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
September 3, 2015 (Actual)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 28, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ADDMEDICA SASA

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Renal Function Disorder
Keywords
Pharmacokinetics of Hydroxyurea

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal-renal function
Arm Type
Experimental
Arm Description
Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Arm Title
Glomerular hyperfiltration
Arm Type
Experimental
Arm Description
Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Arm Title
Moderate renal failure
Arm Type
Experimental
Arm Description
Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2
Intervention Type
Drug
Intervention Name(s)
Siklos
Other Intervention Name(s)
hydroxyurea
Primary Outcome Measure Information:
Title
Measure of Plasmatic Data: Maximum Concentration (Cmax)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Minimum Concentration (Cmin)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Elimination Half-life (T½)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Total Clearance (Cl Tot)
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Plasmatic Data: Distribution Volume
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Title
Measure of Urinary Data: Hydroxyurea Urinary Fractions
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Title
Measure of Urinary Data: Renal Clearance (Cl Renal).
Description
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Time Frame
From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BARTOLUCCI Pablo, MD
Organizational Affiliation
Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
City
Creteil
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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