NCT02522104

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Sep 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 4, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

August 13, 2015

Completed
21 days until next milestone

Study Start

First participant enrolled

September 3, 2015

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
27 days until next milestone

Study Completion

Last participant's last visit for all outcomes

November 28, 2016

Completed
4.7 years until next milestone

Results Posted

Study results publicly available

August 27, 2021

Completed
Last Updated

October 12, 2021

Status Verified

August 1, 2021

Enrollment Period

1.2 years

First QC Date

August 4, 2015

Results QC Date

August 3, 2021

Last Update Submit

September 20, 2021

Conditions

Sickle Cell DiseaseRenal Function Disorder

Keywords

Pharmacokinetics of Hydroxyurea

Outcome Measures

Primary Outcomes (9)

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours

  • 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

    From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours

  • 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

    From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours

Study Arms (3)

Normal-renal function

EXPERIMENTAL

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

Drug: Siklos

Glomerular hyperfiltration

EXPERIMENTAL

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

Drug: Siklos

Moderate renal failure

EXPERIMENTAL

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

Drug: Siklos

Interventions

SiklosDRUG
Also known as: hydroxyurea
Glomerular hyperfiltrationModerate renal failureNormal-renal function

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • Refusal to consent.
  • Patients that do not comply.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Créteil, France

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic Chemicals

Results Point of Contact

Title
Medical director
Organization
Addmedica
corinne.duguet@addmedica.com
+33 1 72 69 01 86

Study Officials

  • BARTOLUCCI Pablo, MD

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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2015

First Posted

August 13, 2015

Study Start

September 3, 2015

Primary Completion

November 1, 2016

Study Completion

November 28, 2016

Last Updated

October 12, 2021

Results First Posted

August 27, 2021

Record last verified: 2021-08

Locations

FR(1)