Sickle Cell DiseasePhase 4NCT02522104

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

A Phase 4 study testing Siklos in people with Sickle Cell Disease and Renal Function Disorder, run by Theravia at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sickle Cell Disease, Renal Function Disorder
What is being tested?: Siklos
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteFrance
Study dates: 3 Sep 2015to 28 Nov 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

France1 site

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

Other trials in France

About this study

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)

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.

Conditions: Sickle Cell Disease, Renal Function Disorder
Being tested: Siklos
Keywords: Pharmacokinetics of Hydroxyurea
Medical subject headings: Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SiklosDrug
Also called hydroxyurea

Study groups in NCT02522104
Study group	Role	What they receive
Normal-renal function	Experimental	Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men Receives: 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. Receives: Drug: Siklos
Moderate renal failure	Experimental	Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2 Receives: Drug: Siklos

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Sep 201528 Nov 2016

First posted13 Aug 2015 (estimated)
Study start3 Sep 2015
Primary completionNov 2016
Study completion28 Nov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02522104
Sponsor's protocol ID: SIK-FR 14-1
Status last verified: Aug 2021
First submitted: 4 Aug 2015
Last updated: 12 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
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Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
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RecruitingPhase 4
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All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02522104
Acronym / sponsor ID: SIK-FR 14-1
Conditions: Sickle Cell Disease, Renal Function Disorder
Keywords: Pharmacokinetics of Hydroxyurea
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: TheraviaIndustry (pharma, biotech, devices)
Study start: 3 Sep 2015 (actual)
Primary completion: Nov 2016 (actual)
Study completion: 28 Nov 2016 (actual)
First posted: 13 Aug 2015 (estimated)
Results: Posted 27 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Normal-renal function	Experimental	Drug: SiklosNormal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Glomerular hyperfiltration	Experimental	Drug: SiklosGlomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Moderate renal failure	Experimental	Drug: SiklosModerate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SiklosAlso: hydroxyurea	Drug	Glomerular hyperfiltration, Moderate renal failure, Normal-renal function

Primary outcome

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
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
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
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
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
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
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
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
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

Results and safety

Results posted to the registry on 27 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal-renal Function	13	10
Glomerular Hyperfiltration	15	12
Moderate Renal Failure	12	5

Primary outcome: 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. Mean (Standard Deviation). Unit: Micromolar

Measure	Normal-renal Function n = 10	Glomerular Hyperfiltration n = 12	Moderate Renal Failure n = 5
Value	271.8 (164.4)	316.8 (73.9)	260.2 (88.1)

Primary outcome: 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. Mean (Standard Deviation). Unit: Micromolar

Measure	Normal-renal Function n = 10	Glomerular Hyperfiltration n = 12	Moderate Renal Failure n = 5
Value	3.80 (2.38)	4.2 (2.2)	7.1 (4.4)

Primary outcome: 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. Mean (Standard Deviation). Unit: Hour

Measure	Normal-renal Function n = 10	Glomerular Hyperfiltration n = 12	Moderate Renal Failure n = 5
Value	0.9 (0.7)	1.0 (0.9)	1.0 (1.1)

Primary outcome: 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. Mean (Standard Deviation). Unit: Hour x Micromolar

Measure	Normal-renal Function n = 10	Glomerular Hyperfiltration n = 12	Moderate Renal Failure n = 5
Value	1144.0 (364.1)	1384.3 (266.5)	1580.6 (540.6)

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal-renal Function	1 of 10 (10%)	2 of 10 (20%)	0 of 10
Glomerular Hyperfiltration	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Moderate Renal Failure	1 of 5 (20%)	0 of 5 (0%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Sickle Cell Disease

Active, not recruitingPhase 1/2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

BARTOLUCCI Pablo, MD principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Siklos in people with Sickle Cell Disease and Renal Function Disorder, run by Theravia at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02522104.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.