ClinicalTrials.gg
Sign In
CompletedNCT02522104Updated Oct 12, 2021Results posted

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

A Phase 4 interventional study of Siklos in Sickle Cell Disease and Renal Function Disorder, sponsored by Theravia. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-12.

Sponsored by Theravia (part of Norgine) · Phase 4, Interventional, and Other

Phase
Phase 4
Study type
Interventional
Enrollment
40
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Sickle Cell Disease
  • Renal Function Disorder

Browse trials for

Keywords

  • Pharmacokinetics of Hydroxyurea
03

In context

Anemia, Sickle Cell

1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.

This study's enrollment of 40 is close to the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

Theravia is the lead sponsor of 8 studies on the registry; 1 is open to participants now.

First submitted before Theravia became part of Norgine.

Browse Theravia studies →All Norgine studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Age ≥ 18 years.
  • Male or female.
  • Sickle cell disease (SS or S-β0thal) confirmed by 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 (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

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 ( \< 30 ml/min).
  • Patients who show toxic signs of bone marrow suppression.
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

05

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • 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

  • 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

  • Experimental
    Moderate renal failure

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

    Drug: Siklos

Interventions

  • DrugSiklos

    Also known as: hydroxyurea

06

What researchers measure

Primary outcomes

  1. 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

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

  2. 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

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

  3. 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

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

  4. 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

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

  5. 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

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

  6. 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

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

  7. 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

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

  8. 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

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

  9. 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

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

07

Results

Posted Aug 27, 2021

Participant flow

Participant flow — Overall Study
MilestoneNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Started131512
Completed10125
Not completed337

Outcome measures

PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Micromolar
Measure of Plasmatic Data: Maximum Concentration (Cmax)
MicromolarNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Maximum Concentration (Cmax)271.8 ± 164.4316.8 ± 73.9260.2 ± 88.1
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Micromolar
Measure of Plasmatic Data: Minimum Concentration (Cmin)
MicromolarNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Minimum Concentration (Cmin)3.80 ± 2.384.2 ± 2.27.1 ± 4.4
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Hour
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
HourNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)0.9 ± 0.71.0 ± 0.91.0 ± 1.1
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Hour x Micromolar
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
Hour x MicromolarNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)1144.0 ± 364.11384.3 ± 266.51580.6 ± 540.6
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Hour
Measure of Plasmatic Data: Elimination Half-life (T½)
HourNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Elimination Half-life (T½)4.30 ± 0.574.75 ± 0.924.98 ± 0.90
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Liter/Hour
Measure of Plasmatic Data: Total Clearance (Cl Tot)
Liter/HourNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Total Clearance (Cl Tot)10.1 ± 4.110.3 ± 1.96.4 ± 2.1
PrimaryMeasure 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

Time frame:
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Reported as:
Mean · Liter
Measure of Plasmatic Data: Distribution Volume
LiterNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Plasmatic Data: Distribution Volume61.2 ± 20.370.3 ± 16.244.2 ± 11.4
PrimaryMeasure 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

Time frame:
From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Reported as:
Mean · Percentage urinary excretion
Measure of Urinary Data: Hydroxyurea Urinary Fractions
Percentage urinary excretionNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Urinary Data: Hydroxyurea Urinary Fractions35.8 ± 10.244.3 ± 9.620.2 ± 7.3
PrimaryMeasure 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

Time frame:
From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Reported as:
Mean · Liter/Hour
Measure of Urinary Data: Renal Clearance (Cl Renal).
Liter/HourNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Measure of Urinary Data: Renal Clearance (Cl Renal).3.9 ± 1.64.7 ± 1.31.3 ± 0.7

Adverse events

Collected over From the signature of the informed consent form by the patient until 7 days after the end of the follow-up for the study. Duration of participation for each patients : 9 to 40 days depending on the concomitant treatments.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Normal-renal Function0/10 (0%)1/10 (10%)2/10 (20%)
Glomerular Hyperfiltration0/12 (0%)0/12 (0%)0/12 (0%)
Moderate Renal Failure0/5 (0%)1/5 (20%)0/5 (0%)
Most frequent serious events
Most frequent serious events
EventNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
Vaso-occlusive crisisVascular disorders0/100/121/5
Aplastic anemiaBlood and lymphatic system disorders1/100/120/5
HypotensionCardiac disorders1/100/120/5
Most frequent other events
Most frequent other events
EventNormal-renal FunctionGlomerular HyperfiltrationModerate Renal Failure
OverdoseInjury, poisoning and procedural complications1/100/120/5
FeverGeneral disorders1/100/120/5

Baseline characteristics

Age, Continuous
Age, Continuous(years)Normal-renal FunctionGlomerular HyperfiltrationModerate Renal FailureTotal
Mean31.2 ± 4.827.8 ± 7.650.0 ± 7.533.1 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)Normal-renal FunctionGlomerular HyperfiltrationModerate Renal FailureTotal
Female511218
Male5139
08

Study locations

1 site
  • Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor
    Creteil, France
09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Sep 2015 to primary completion in Nov 2016, 14 months.

Results were first posted in Aug 2021, 4 years 9 months after primary completion.

Of 20 phase 4 interventional studies under Anemia, Sickle Cell, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 41. This study's 14 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 4, 2015
First posted
Aug 13, 2015
StartActual
Sep 3, 2015
Primary completionActual
Nov 2016
CompletionActual
Nov 28, 2016
Results first posted
Aug 27, 2021
Last update
Oct 12, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Oct 12, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02522104
Lead sponsor
Theravia
Responsible party
Sponsor
First posted
Aug 13, 2015
Start date
Sep 3, 2015
Primary completion
Nov 2016
Completion
Nov 28, 2016
Results posted
Aug 27, 2021
Last update
Oct 12, 2021

Study contacts

BARTOLUCCI Pablo, MD
principal investigator · Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Hydroxyurea

Other studies in this condition

Anemia, Sickle Cell →

Other studies from this sponsor

Theravia →

Start the discussion