A Single Bolus, 12-hour Euglycemic Clamp Study of the Safety, Pharmacokinetics (PK) and Glucodynamics (GD) of Intraperitoneal (IP) Portal Insulin U-500
The goal of this clinical trial is to assess the safety of a new U500 insulin formulation and to determine how rapidly it is absorbed and how long it takes to act when administered intraperitoneally. The trial will be conducted in people with Type 1 Diabetes. The main questions it aims to answer are: Is the drug safe and tolerable when administered intraperitoneally? How fast is it absorbed, and how long does it take to act? Researchers will compare the investigational product (PI-U500) with Humulin R U500 administered intraperitoneally and Lyumjev U100 administered subcutaneously. Participants will undergo a 12-hour clamp procedure in which their blood glucose will be maintained stable via glucose infusion at variable rates after a single intraperitoneal injection of the insulin formulation.
• Subjects who meet all the following criteria at Screening will be included in the study:
‣ Subjects ≥18 to ≤60 years of age at the time of signing the informed consent.
⁃ Subjects diagnosed with T1DM for at least 12 months.
⁃ Subjects who have been using an approved insulin pump or use MDI with basal and bolus insulin (stable use for 3 months).
⁃ Fasting C-peptide concentration of ≤0.3 nmol/L (0.9061 ng/ml), assessed at a plasma glucose concentration \>90 mg/dL. (If necessary, the subject may consume carbohydrates to raise BG over 90 mg/dL as measured by YSI (glucose analyzer) prior to drawing blood for C-peptide. This may be repeated as needed to ensure C-peptide is assessed when plasma glucose concentration is \>90 mg/dL).
⁃ HbA1c concentration of ≤8.5%.
⁃ Body mass index (BMI) within the range ≥18.5 to ≤30.0 kg/m2.
⁃ Weight ≥ 50 kg.
⁃ Female subjects must be non-pregnant and non-lactating and postmenopausal (no menses \>12 months); postmenopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at Screening for all female subjects.
⁃ Male subjects must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, the subject and his partner must be using acceptable methods of contraception.
‣ Has venous access sufficient to allow for blood sampling.
‣ Capable of giving signed informed consent and willing to follow study procedures and commitment to the study duration.