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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02522104
Recruitment Status : Completed
First Posted : August 13, 2015
Results First Posted : August 27, 2021
Last Update Posted : October 12, 2021
Sponsor:
Information provided by (Responsible Party):
ADDMEDICA SASA

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Sickle Cell Disease
Renal Function Disorder
Intervention Drug: Siklos
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Period Title: Overall Study
Started 13 15 12
Completed 10 12 5
Not Completed 3 3 7
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure Total
Hide Arm/Group Description Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men. Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2 Total of all reporting groups
Overall Number of Baseline Participants 10 12 5 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 12 participants 5 participants 27 participants
31.2  (4.8) 27.8  (7.6) 50.0  (7.5) 33.1  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 12 participants 5 participants 27 participants
Female 5 11 2 18
Male 5 1 3 9
1.Primary Outcome
Title Measure of Plasmatic Data: Maximum Concentration (Cmax)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Micromolar
271.8  (164.4) 316.8  (73.9) 260.2  (88.1)
2.Primary Outcome
Title Measure of Plasmatic Data: Minimum Concentration (Cmin)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Micromolar
3.80  (2.38) 4.2  (2.2) 7.1  (4.4)
3.Primary Outcome
Title Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Hour
0.9  (0.7) 1.0  (0.9) 1.0  (1.1)
4.Primary Outcome
Title Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Hour x Micromolar
1144.0  (364.1) 1384.3  (266.5) 1580.6  (540.6)
5.Primary Outcome
Title Measure of Plasmatic Data: Elimination Half-life (T½)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Hour
4.30  (0.57) 4.75  (0.92) 4.98  (0.90)
6.Primary Outcome
Title Measure of Plasmatic Data: Total Clearance (Cl Tot)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with Glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with Moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Liter/Hour
10.1  (4.1) 10.3  (1.9) 6.4  (2.1)
7.Primary Outcome
Title Measure of Plasmatic Data: Distribution Volume
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with Normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with Glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with Moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Liter
61.2  (20.3) 70.3  (16.2) 44.2  (11.4)
8.Primary Outcome
Title Measure of Urinary Data: Hydroxyurea Urinary Fractions
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with Normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with Glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with Moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Percentage urinary excretion
35.8  (10.2) 44.3  (9.6) 20.2  (7.3)
9.Primary Outcome
Title Measure of Urinary Data: Renal Clearance (Cl Renal).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description:
Patients with Normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
Patients with Glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
Patients with Moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
Overall Number of Participants Analyzed 10 12 5
Mean (Standard Deviation)
Unit of Measure: Liter/Hour
3.9  (1.6) 4.7  (1.3) 1.3  (0.7)
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Hide Arm/Group Description Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men. Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
All-Cause Mortality
Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/12 (0.00%)   0/5 (0.00%) 
Hide Serious Adverse Events
Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/10 (10.00%)   0/12 (0.00%)   1/5 (20.00%) 
Blood and lymphatic system disorders       
Aplastic anemia *  1/10 (10.00%)  0/12 (0.00%)  0/5 (0.00%) 
Cardiac disorders       
Hypotension *  1/10 (10.00%)  0/12 (0.00%)  0/5 (0.00%) 
Vascular disorders       
Vaso-occlusive crisis *  0/10 (0.00%)  0/12 (0.00%)  1/5 (20.00%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Normal-renal Function Glomerular Hyperfiltration Moderate Renal Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/10 (20.00%)   0/12 (0.00%)   0/5 (0.00%) 
General disorders       
Fever *  1/10 (10.00%)  0/12 (0.00%)  0/5 (0.00%) 
Injury, poisoning and procedural complications       
Overdose *  1/10 (10.00%)  0/12 (0.00%)  0/5 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical director
Organization: Addmedica
Phone: +33 1 72 69 01 86
EMail: corinne.duguet@addmedica.com
Layout table for additonal information
Responsible Party: ADDMEDICA SASA
ClinicalTrials.gov Identifier: NCT02522104    
Other Study ID Numbers: SIK-FR 14-1
First Submitted: August 4, 2015
First Posted: August 13, 2015
Results First Submitted: August 3, 2021
Results First Posted: August 27, 2021
Last Update Posted: October 12, 2021