Trial Outcomes & Findings for Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH) (NCT NCT02522104)
NCT ID: NCT02522104
Last Updated: 2021-10-12
Results Overview
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
40 participants
Primary outcome timeframe
0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Results posted on
2021-10-12
Participant Flow
Participant milestones
| Measure |
Normal-renal Function
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men
|
Moderate Renal Failure
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Overall Study
STARTED
|
13
|
15
|
12
|
|
Overall Study
COMPLETED
|
10
|
12
|
5
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
Baseline characteristics by cohort
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
31.2 years
STANDARD_DEVIATION 4.8 • n=99 Participants
|
27.8 years
STANDARD_DEVIATION 7.6 • n=107 Participants
|
50.0 years
STANDARD_DEVIATION 7.5 • n=206 Participants
|
33.1 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Maximum Concentration (Cmax)
|
271.8 Micromolar
Standard Deviation 164.4
|
316.8 Micromolar
Standard Deviation 73.9
|
260.2 Micromolar
Standard Deviation 88.1
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Minimum Concentration (Cmin)
|
3.80 Micromolar
Standard Deviation 2.38
|
4.2 Micromolar
Standard Deviation 2.2
|
7.1 Micromolar
Standard Deviation 4.4
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
|
0.9 Hour
Standard Deviation 0.7
|
1.0 Hour
Standard Deviation 0.9
|
1.0 Hour
Standard Deviation 1.1
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
|
1144.0 Hour x Micromolar
Standard Deviation 364.1
|
1384.3 Hour x Micromolar
Standard Deviation 266.5
|
1580.6 Hour x Micromolar
Standard Deviation 540.6
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Elimination Half-life (T½)
|
4.30 Hour
Standard Deviation 0.57
|
4.75 Hour
Standard Deviation 0.92
|
4.98 Hour
Standard Deviation 0.90
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Total Clearance (Cl Tot)
|
10.1 Liter/Hour
Standard Deviation 4.1
|
10.3 Liter/Hour
Standard Deviation 1.9
|
6.4 Liter/Hour
Standard Deviation 2.1
|
PRIMARY outcome
Timeframe: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Plasmatic Data: Distribution Volume
|
61.2 Liter
Standard Deviation 20.3
|
70.3 Liter
Standard Deviation 16.2
|
44.2 Liter
Standard Deviation 11.4
|
PRIMARY outcome
Timeframe: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Urinary Data: Hydroxyurea Urinary Fractions
|
35.8 Percentage urinary excretion
Standard Deviation 10.2
|
44.3 Percentage urinary excretion
Standard Deviation 9.6
|
20.2 Percentage urinary excretion
Standard Deviation 7.3
|
PRIMARY outcome
Timeframe: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hoursCompare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Outcome measures
| Measure |
Normal-renal Function
n=10 Participants
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 Participants
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 Participants
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Measure of Urinary Data: Renal Clearance (Cl Renal).
|
3.9 Liter/Hour
Standard Deviation 1.6
|
4.7 Liter/Hour
Standard Deviation 1.3
|
1.3 Liter/Hour
Standard Deviation 0.7
|
Adverse Events
Normal-renal Function
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Glomerular Hyperfiltration
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Moderate Renal Failure
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Normal-renal Function
n=10 participants at risk
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 participants at risk
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 participants at risk
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Aplastic anemia
|
10.0%
1/10 • 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.
|
0.00%
0/12 • 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.
|
0.00%
0/5 • 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.
|
|
Cardiac disorders
Hypotension
|
10.0%
1/10 • 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.
|
0.00%
0/12 • 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.
|
0.00%
0/5 • 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.
|
|
Vascular disorders
Vaso-occlusive crisis
|
0.00%
0/10 • 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.
|
0.00%
0/12 • 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.
|
20.0%
1/5 • 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
| Measure |
Normal-renal Function
n=10 participants at risk
Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
|
Glomerular Hyperfiltration
n=12 participants at risk
Patients with glomerular renal hyperfiltration defined by GFR \> 130 mL/min/1.73m2 in women and GFR \> 140 mL/min/1.73m2 in men.
|
Moderate Renal Failure
n=5 participants at risk
Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Overdose
|
10.0%
1/10 • 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.
|
0.00%
0/12 • 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.
|
0.00%
0/5 • 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.
|
|
General disorders
Fever
|
10.0%
1/10 • 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.
|
0.00%
0/12 • 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.
|
0.00%
0/5 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place