Clinical trial NCT05711381: Phase 1 Study of PK and Safety of HM15912 (Sonefpeglutide) in Subjects With Normal and Severe Kidney Function
Official title: An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912(Sonefpeglutide) in Subjects With Renal Impairment and Matched Control Subjects With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Hanmi Pharmaceutical Company Limited
Sponsor class: INDUSTRY
First posted: 2023-02-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Exclusion Criteria for Subjects with Normal Renal Function

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (GI), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at the time of dosing).
* Subject who had a mean BP ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 140mmHg (systolic) or ≥ 90 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
* Subject who had a baseline corrected QT using the Fridericia correction formula (QTcF) \> 450 msec in males or QTcF \> 470 msec in females.

Additional Exclusion Criteria for Subjects with Impaired Renal Function

* Subject with clinically significant active diseases that may have affected the safety of the subject or that may have affected the PK of HM15912 (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at time of dosing). Subjects with any significant hepatic, cardiac, or pulmonary disease or subjects who were clinically nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart disease, etc. were not causes for exclusion as long as the subject was medically stable and any drugs that were administered for these conditions were not expected to interfere with the PK of HM15912.
* Subject who had a mean BP ≥ 180 mm Hg (systolic) or ≥ 120 mm Hg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 180 mm Hg (systolic) or ≥ 120 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
* Subject who had a baseline QTcF \> 480 msec.

Primary outcomes:
measure: Maximum Serum Concentration (Cmax) of HM15912
timeFrame: Day 1 to 29 (Total duration: 29 days)
measure: Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912
timeFrame: Day 1 to 29 (Total duration: 29 days)
Secondary outcomes:
measure: Overall Summary of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 29
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Knoxville
country: United States
facility: AMR Knoxville
state: Tennessee
Study officials:
References: