Renal Impairment
Conditions
Brief summary
An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912 in Subjects with Renal Impairment and Matched Control Subjects with Normal Renal Function
Detailed description
A single-dose, open-label, Phase 1 study (HM-GLP2-102) was conducted to evaluate the impact of renal impairment (RI) on the pharmacokinetics (PK) of HM15912. This study aimed to assess the safety and PK profile of HM15912 at a minimum effective dose of 0.5 mg/kg, which was determined based on findings from a previous clinical study (HM-GLP2-101). The study was initially designed to be conducted in two parts. Part 1: An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with severe RI and subjects with normal renal function as a control group. Part 2 (if applicable): An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with moderate and mild RI.
Interventions
DRUGHM15912
Singe subcutaneous administration of HM15912 0.5 mg/kg
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
All Subjects * Subjects voluntarily agreed to participate in this study and sign an institutional review board (IRB)-approved informed consent form prior to performing any of the S1 procedures. * Males and females ≥ 18 and ≤ 80 years of age at S1. * Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m\^2. Subjects with Normal Renal Function * No clinically relevant abnormalities identified by detailed medical history, full physical examination, including blood pressure (BP) and heart rate (HR) measurements, 12-lead ECG, and clinical laboratory tests. * Normal renal function (eGFR ≥ 90 mL/min/1.73m\^2) at screening based on the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. * Demographically comparable to the group of subjects with impaired renal function. Subjects with Impaired Renal Function * Met the following eGFR criteria during the screening period based on the CKD-EPI equation: 1. Severe renal impairment: eGFR \< 30 mL/min/1.73m\^2, but not requiring hemodialysis. 2. Moderate renal impairment: 30 mL/min/1.73m\^2 ≤ eGFR \< 60 mL/min/1.73m\^2 3. Mild renal impairment: 60 mL/min/1.73m\^2 ≤ eGFR \< 90 mL/min/1.73m\^2
Exclusion criteria
All Subjects: * Renal transplant recipients or subjects requiring hemodialysis and peritoneal dialysis. * Subject with a history or presence of any psychiatric disorder that, in the opinion of the Investigator, might have confounded the results of the study or posed additional risk in administering the IP to the subject. * Had participated in an interventional clinical trial (investigational or marketed product) within 1 month of screening or 5 half-lives of the drug under investigation (whichever came first), or planned to participate in another clinical trial. * Subject with a history of any SAEs, hypersensitivity reactions, or intolerance to IP components. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912 | Day 1 to 29 (Total duration: 29 days) | PK samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method. |
| Maximum Serum Concentration (Cmax) of HM15912 | Day 1 to 29 (Total duration: 29 days) | Pharmacokinetic (PK) samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Day 1 up to Day 29 | The number and percentages of subjects with TEAEs were to be summarized by cohort. A TEAE was defined as any AE that began, or worsened in severity, on or after the date of the first IP administration until the last follow-up visit. |
Countries
United States
Participant flow
Pre-assignment details
A single-dose, open-label, phase 1 study, which was to characterize the effect of RI on the PK of HM15912, was planned to be conducted in 2 parts. A total of 16 subjects, 8 subjects with severe RI (Cohort 2) and 8 subjects with normal renal function (Cohort 1), were enrolled for Part 1. Part 2 of the study, which was optional to evaluate the effect of moderate and mild renal impairment on the PK of HM15912 following a single SC dose, was not conducted based on the results from Part 1.
Participants by arm
| Arm | Count |
|---|---|
| Severe Renal Impairment Subjects with eGFR \< 30 mL/min/1.73m\^2, but not requiring hemodialysis, received 0.5 mg/kg SC dose of HM15912 on Day 1. | 8 |
| Normal Renal Function Subjects with eGFR≥ 90 mL/min/1.73m\^2 received 0.5 mg/kg SC dose of HM15912 on Day 1. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Severe Renal Impairment | Normal Renal Function | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 12 Participants |
| Age, Continuous | 63.3 years STANDARD_DEVIATION 8.35 | 59.6 years STANDARD_DEVIATION 3.25 | 61.4 years STANDARD_DEVIATION 6.4 |
| Estimated glomerular filtration rate | 17.145 mL/min/1.73m^2 STANDARD_DEVIATION 7.5206 | 97.864 mL/min/1.73m^2 STANDARD_DEVIATION 4.2156 | 57.504 mL/min/1.73m^2 STANDARD_DEVIATION 42.097 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912
PK samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.
Time frame: Day 1 to 29 (Total duration: 29 days)
Population: PK Population: All subjects who had at least one evaluable HM15912 serum concentration after receiving any amount of HM15912 without IPDs or events.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912 | 1117469.3 h*ng/mL | Standard Deviation 347572.67 |
| Normal Renal Function | Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912 | 890343.8 h*ng/mL | Standard Deviation 235565.36 |
90% CI: [0.93, 1.68]
Primary
Maximum Serum Concentration (Cmax) of HM15912
Pharmacokinetic (PK) samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.
Time frame: Day 1 to 29 (Total duration: 29 days)
Population: PK population: All subjects who had at least one evaluable HM15912 serum concentration after receiving any amount of HM15912 without IPDs or events.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | Maximum Serum Concentration (Cmax) of HM15912 | 2811.25 ng/mL | Standard Deviation 1498.985 |
| Normal Renal Function | Maximum Serum Concentration (Cmax) of HM15912 | 3000.00 ng/mL | Standard Deviation 1174.114 |
90% CI: [0.59, 1.41]
Secondary
Overall Summary of Treatment-emergent Adverse Events (TEAEs)
The number and percentages of subjects with TEAEs were to be summarized by cohort. A TEAE was defined as any AE that began, or worsened in severity, on or after the date of the first IP administration until the last follow-up visit.
Time frame: Day 1 up to Day 29
Population: Safety Population: All subjects who received any amount of HM15912.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Severe Renal Impairment | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Related Adverse Events (TRAEs) | 0 Participants |
| Severe Renal Impairment | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs leading to Drug Interruption/Withdrawn | 0 Participants |
| Severe Renal Impairment | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Emergent Serious Adverse Events (TESAEs) | 0 Participants |
| Severe Renal Impairment | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | any TEAEs Leading to Death | 0 Participants |
| Severe Renal Impairment | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Normal Renal Function | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | any TEAEs Leading to Death | 0 Participants |
| Normal Renal Function | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Normal Renal Function | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Related Adverse Events (TRAEs) | 0 Participants |
| Normal Renal Function | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any Treatment-Emergent Serious Adverse Events (TESAEs) | 0 Participants |
| Normal Renal Function | Overall Summary of Treatment-emergent Adverse Events (TEAEs) | Any TEAEs leading to Drug Interruption/Withdrawn | 0 Participants |