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This is an open-label, non-randomized, parallel cohorts design, multicenter, single dose phase I study.
The primary objectives are:
To evaluate the pharmacokinetics (plasma and urine) profile of HRS-9231 following single intravenous injection (0.05 mmol/kg body weight) in patients with mild to severe renal impairment and in healthy volunteers with normal renal function used as reference.
To assess dialysability of HRS-923 following a single intravenous injection (0.05 mmol/kg body weight) in patients with end stage renal disease requiring hemodialysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | Healthy volunteer with stable normal renal function defined with an absolute value of eGFR ≥ 90 and < 130 mL/min based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 25% between the 2 measurements. |
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| Cohort B | Experimental | Patient with stable mild renal impairment defined with an absolute value of eGFR ≥ 60 and <90 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 25% between the 2 measurements. |
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| Cohort C | Experimental | Patient with stable moderate renal impairment defined with an absolute value of eGFR between ≥ 30 and <60 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements. |
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| Cohort D | Experimental | Patient with stable severe renal impairment defined with an absolute value of eGFR between ≥ 15 and <30 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements. |
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| Cohort E | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HRS-9231 | Drug | HRS-9231 |
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| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Observed maximum plasma concentration. Blood samples will be collected. | Prior to HRS-9231 administration and Day 5 (for all cohorts) or Day 6 (only for cohort D). |
| AUC0-t | Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration. Blood samples will be collected. | Prior to HRS-9231 administration and Day 5 (for all cohorts) or Day 6 (only for cohort D). |
| AUC0-∞ | Area under the plasma concentration-time curve from time 0 to infinity. Blood samples will be collected. | Prior to HRS-9231 administration and Day 5 (for all cohorts) or Day 6 (only for cohort D). |
| Tmax | Observed time to reach C(max). Blood samples will be collected. | Prior to HRS-9231 administration and Day 5 (for all cohorts) or Day 6 (only for cohort D). |
| Ae | Amount excreted. Urine samples will be collected. | Prior to HRS-9231 administration and Day 5 (for all cohorts) or within 6 days (only for cohort D) after administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment emergent AEs (TEAEs) | From screening visit to 6 months after administration. |
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Inclusion Criteria:
Male or female subjects, ages 18 to 65, inclusive, at the time of informed consent.
Female subjects weigh ≥ 45 kg, male subjects weigh ≥ 50 kg, and BMI between 18.0 and 28.0 kg/m2, inclusive, at screening.
Have an eGFR expressed in mL/min/1.73m2 (MDRD formula estimation) at screening within the range of:
Cohort A - normal renal function: ≥ 90 mL/min and < 130 mL/min; Cohort B - mild renal impairment: 60 < 90 mL/min; Cohort C - moderate renal impairment: 30 < 60 mL/min; Cohort D - severe renal impairment: 15 < 30 mL/min; Cohort E - ESRD subjects requiring HD: < 15 mL/min.
The renal function is required to be stable. The interval between two assessments during the screening period should be at least 72 hours apart (the first renal function assessment result may use historical values with 30 days before screening), and the two assessments should be consistent with the same renal function classification and two values have to show ≤25%. If the two assessments are inconsistent in terms of renal function category, the third assessment has to be conducted at least 72 hours after the second assessment. If the second and third assessments differ, the subject will be ineligible for the study.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shandong First Medical University First Affiliated Hospital (Shandong Qianfoshan Hospital) | Jinan | Shandong | 250014 | China |
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Patient with end-stage renal failure who requires 3 hemodialysis sessions per week and defined with an absolute value of eGFR <15 mL/min.
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