A Single Bolus, 12-hour Euglycemic Clamp Study of the Safety, Pharmacokinetics (PK) and Glucodynamics (GD) of Intraperitoneal (IP) Portal Insulin U-500

NCT07341373 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PDI-PIU500-C001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Insulin; Intraperitoneal; Euglycemic Clamp; Diabetes Mellitus; Human Insulin

Outcome Measures

Primary Outcomes (17)

• Safety: Incidence of adverse events

  From enrollment until the follow-up visit, an average of 2 months

• Safety: Change from baseline in systolic and diastolic blood pressure

  Will be measured at 2 times, first within 4 hours before drug administration (Pre-clamp) and then after 12 hours of drug administration (post-clamp)

• Safety: Change from baseline in temperature

  Will be measured at 2 times, first within 4 hours before drug administration (Pre-clamp) and then after 12 hours of drug administration (post-clamp)

• Safety: Change from baseline in respiratory rate

  Will be measured at 2 times, first within 4 hours before drug administration (Pre-clamp) and then after 12 hours of drug administration (post-clamp)

• Safety: Change from baseline in heart rate

  Will be measured at 2 times, first within 4 hours before drug administration (Pre-clamp) and then after 12 hours of drug administration (post-clamp)

• Safety: Change from baseline in 12-lead electrocardiogram (ECG) parameters

  The following parameters will be recorded from the subject's ECG trace as calculated by the machine algorithm: heart rate, QT interval, PR interval, QRS interval, RR interval, and QTc (corrected) using the Fridericia correction (QTcF = QT ÷ cube root of the R-R interval \[where R-R is the duration of the entire cardiac cycle\]).

  Pre-dose and after the end of PK-sampling (720 minutes post-dose)

• Safety: Incidence and severity of clinical findings on physical examination

  Pre-dose and after the end of PK-sampling (720 minutes post-dose)

• Tolerability: Pain assessments per Visual Analogue Scale (VAS)

  VAS assessment will target the assessment of abdominal pain. The scale will go from 0 to 10, with 10 being the maximum pain.

  10 min and 1 hour post-dosing

• Tolerability: Change in Interleukin 6 [IL-6] levels

  Blood samples will be taken immediately before dosing, 2 hours after dosing, and with the last PK sample (720 minutes after dosing)

• Tolerability: Change in tumor necrosis factor [TNF-α] levels

  Blood samples will be taken immediately before dosing, 2 hours after dosing, and with the last PK sample (720 minutes after dosing)

• Tolerability: Change in high sensitivity C-reactive protein [hsCRP] levels

  Blood samples will be taken immediately before dosing, 2 hours after dosing, and with the last PK sample (720 minutes after dosing)

• Pharmacokinetic: Area under the insulin concentration-time curve (AUC)

  For the duration of the euglycemic clamp

  From the time of dose (time 0) until 12 hours post-dose (AUCIns,0-12h)

• Pharmacokinetic: Maximum insulin concentration (Cmax)

  Over 12 hours post-dosing

• Pharmacokinetic: Time to maximum insulin concentration (Tmax)

  Over 12 hours post-dosing

• Glucodynamic: Area under the glucose infusion rate (GIR) time curve

  From the time of dose (time 0) until 12 hours post-dose (AUCGIR,0-12h)

• Glucodynamic: Maximum GIR (GIRmax)

  Over 12 hours post-dosing

• Glucodynamic: Time to maximum GIR (TGIRmax)

  Over 12 hours post-dosing

Secondary Outcomes (7)

• Pharmacokinetic: Area under the partial insulin concentration-time curves (AUC) in time intervals

  From 0 to 15 minutes (AUCIns,0-15 min), from 0-30 minutes (AUCIns,0-30 min) and from 3 hours to end (AUCIns,3h-end)

• Pharmacokinetic: Time to half-maximum insulin concentration before Cmax (t50%-INS (early))

  Over 12 hour post-dosing

• Pharmacokinetic: Time to half-maximum insulin concentration after Cmax (t50%-INS (late))

  Over 12 hours post-dosing

• Pharmacokinetic: Onset of appearance

  Over 12 hours post-dosing

• Glucodynamic: Area under GIR time curve in time intervals

  From 0-30 minutes (AUCGIR,0-30 min), from 0 to 1 hour (AUCGIR,0-1h), from 4 hours to end (AUCGIR,4h-end), from 0 to 6 hours (AUCGIR,0-6h) and from 0 to end (AUCGIR,0-end)

Study Arms (6)

Part A, Group 1, Single Ascending Dose

EXPERIMENTAL

Participants will receive PI-U500 intraperitoneally at 0.1 U/kg, then 0.2 U/kg and lastly 0.3 U/kg

Drug: Portal Insulin U-500

Part B, Group 2

OTHER

A three-way crossover where participants will receive 0.1 U/kg of PI-U500, followed by 0.2 U/kg of Humulin R U500 (Active Control), and finally 0.2 U/kg of PI-U500. All administered intraperitoneally.

Drug: Portal Insulin U-500; Drug: Humulin R U-500

Part B, Group 3

OTHER

A three-way crossover where participants will receive 0.1 U/kg of PI-U500, followed by 0.2 U/kg of Humulin R U500 (Active Control), and finally 0.3 U/kg of PI-U500. All administered intraperitoneally.

Drug: Portal Insulin U-500; Drug: Humulin R U-500

Part B, Group 4

OTHER

A three-way crossover where participants will receive 0.2 U/kg of Lyumjev U-100 (Active Control) subcutaneously, followed by 0.2 U/kg of PI-U500 intraperitoneally, and finally 0.3 U/kg of PI-U500, also intraperitoneally.

Drug: Portal Insulin U-500; Drug: Lyumjev U-100 Insulin

Part B, Group 5

OTHER

A two-way crossover where participants will receive 0.2 U/kg of Lyumjev U-100 (Active Control) subcutaneously, followed by 0.2 U/kg of PI-U500 intraperitoneally.

Drug: Portal Insulin U-500; Drug: Lyumjev U-100 Insulin

Part B, Group 6

OTHER

A three-way crossover where participants will receive 0.2 U/kg of each of the drugs sequentially, but the order will be randomized into three options: * Option 1: 0.2 U/kg of Lyumjev U-100 (Active Control) subcutaneously, followed by 0.2 U/kg of Humulin R U500 (Active Control) intraperitoneally, and finally 0.2 U/kg of PI-U500 intraperitoneally. * Option 2: 0.2 U/kg of Humulin R U500 (Active Control) intraperitoneally , followed by 0.2 U/kg of PI-U500 intraperitoneally, and finally 0.2 U/kg of Lyumjev U-100 (Active Control) subcutaneously. * Option 3: 0.2 U/kg of PI-U500 intraperitoneally , followed by 0.2 U/kg of Lyumjev U-100 (Active Control) subcutaneously, and finally 0.2 U/kg of Humulin R U500 (Active Control) intraperitoneally.

Drug: Portal Insulin U-500; Drug: Humulin R U-500; Drug: Lyumjev U-100 Insulin

Interventions

Portal Insulin U-500 DRUG

Intraperitoneal delivery of a single dose at 0.1 U/kg during an euglycemic clamp

Also known as: PI-U500

Part A, Group 1, Single Ascending Dose; Part B, Group 2; Part B, Group 3

Humulin R U-500 DRUG

Intraperitoneal delivery of a single dose at 0.2 U/kg during an euglycemic clamp

Part B, Group 2; Part B, Group 3; Part B, Group 6

Lyumjev U-100 Insulin DRUG

Subcutaneous delivery of a single dose at 0.2 U/kg during an euglycemic clamp

Part B, Group 4; Part B, Group 5; Part B, Group 6

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participating in the study:
• A subject who has proliferative retinopathy or maculopathy (based on records/documentation of ophthalmologic exam within 18 months of Screening or ophthalmologic exam during Screening), severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
• History of ≥2 episodes of severe hypoglycemia (as defined per ADA criteria) or ≥1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within 6 months prior to Screening.
• Subject is not able to avoid major dietary changes for the duration of the study.
• Systolic blood pressure \>150 mm Hg and/or diastolic blood pressure \>90 mm Hg at Screening. Treatment with no more than 2 antihypertensive medications must be with stable doses for at least 3 months prior to Screening.
• Current use of any drugs as listed in the table of prohibited medications.
• History of any major surgery within 6 months prior to Screening.
• History of any serious allergic adverse reaction or hypersensitivity to any of the product components.
• History of renal disease or abnormal kidney function tests at Screening (GFR \<60 mL/min/1.73m2 as estimated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]).
• Triglycerides \>500 mg/dL at Screening.
• Clinically significant abnormal hematology or biochemistry screening tests. Subjects may have these labs be redrawn once on a separate day.
• Any history of heart disease, defined as symptomatic heart failure (New York Heart Association class III or IV), myocardial infarction, coronary artery bypass graft surgery, or angioplasty, unstable angina requiring medication, transient ischemic attack, cerebral infarct, or cerebral hemorrhage.
• Presence of clinically significant physical, laboratory, or ECG findings (eg, QTcF \>450 msec for males, QTcF \>470 msec for females) at Screening that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results.
• History or presence of malignant neoplasms within the past 5 years prior to the day of Screening. Basal and squamous cell skin cancer and any in-situ carcinomas are allowed.
• Clinically significant concomitant disease including cardiovascular, renal, hepatic, respiratory, gastrointestinal, hematological, dermatological, neurological, psychiatric, systemic or infections disease as judged by the Investigator.

Sponsors & Collaborators

• Portal Diabetes, Inc.: lead

Study Sites (1)

ProSciento, Inc.

Chula Vista, California, 91911, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will be conducted in 2 parts. Part A will comprise of a three-way crossover, single ascending doses (SAD) of 3 different dose levels of PI-U500 using a euglycemic clamp. Part B will comprise of a randomized, open-label, two-way and three-way crossover comparative single dose assessment of PI-U500 versus Humulin® R U-500 administered IP versus Lyumjev® U-100 subcutaneously (SC) using a euglycemic clamp.

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: January 14, 2026
• Study Start: February 10, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2025-11

Locations

US (1)