Subcutaneous Pharmacokinetic Evaluation of Monomeric Insulin and Lyumjev in Adults With Type 1 Diabetes

NCT07090824 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 710302R56DK119254-06
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The SPEED study is a randomized, crossover pilot study evaluating the pharmacokinetics of novel insulin formulations in adults with type 1 diabetes. The study compares two experimental insulin formulations (diluted U-200 Humalog and U-500 Humulin with sterile water, mannitol and EDTA) against commercially available U-100 Lyumjev to determine if these modifications can improve insulin onset and duration of action. Twenty participants will complete three study visits, each separated by at least48 hours. At each visit, participants will receive one of the three insulin formulations (0.20 u/kg) via subcutaneous injection following consumption of a standardized mixed meal. Blood samples will be collected frequently over 6 hours to measure insulin concentrations and assess pharmacokinetic parameters, including time to maximum concentration (Tmax), maximum concentration (Cmax), elimination half-life, and area under the curve. The study aims to address limitations of current insulin formulations used in automated insulin delivery systems, which are too slow to provide optimal meal coverage without pre-meal dosing. By reducing zinc content through EDTA chelation and decreasing metacresol concentration through dilution, these novel formulations may offer faster onset and shorter duration of action, potentially improving glucose control in people with type 1 diabetes using insulin pump therapy.

Conditions

Type 1 Diabetes Mellitus; Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; T1D; Insulin-Dependent Diabetes Mellitus; Pharmacokinetics; Insulin; Subcutaneous Insulin; Drug: Insulin Lispro; Drug: Insulin Regular; Drug: Modified Insulin Formulations; Drug: Insulin Lispro-aabc; Insulin formulation; Monomeric Insulin

Outcome Measures

Primary Outcomes (4)

• Time to Maximum Insulin Concentration (Tmax)

  Time from insulin injection to maximum plasma insulin concentration for each insulin formulation, determined from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).

  0 to 360 minutes post-injection

• Maximum Plasma Insulin Concentration (Cmax)

  Peak plasma insulin concentration achieved for each insulin formulation, determined from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).

  0 to 360 minutes post-injection

• Elimination Half-Life (T1/2)

  Time required for plasma insulin concentration to decrease by 50% from maximum concentration for each insulin formulation, calculated from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).

  0 to 360 minutes post-injection

• Area Under the Concentration-Time Curve (AUC)

  Total drug exposure calculated as the area under the plasma insulin concentration-time curve using the trapezoidal rule. Provides a weighted sum of insulin concentration values over time for each formulation. Measured using validated enzyme-linked immunosorbent assay (ELISA)

  0 to 360 minutes post-injection

Study Arms (3)

Diluted Humalog U-200 Insulin

EXPERIMENTAL

Participants will receive 0.20u/kg U-200 Humalog diluted 1:1 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection

Drug: Diluted Humalog U-200 Insulin; Dietary Supplement: Boost Mixed Meal Test

Diluted Humulin U-500 Insulin

EXPERIMENTAL

Participants will receive 0.20u/kg U-500 Humulin diluted 1:4 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection

Drug: Diluted U-500 Humulin Insulin; Dietary Supplement: Boost Mixed Meal Test

Lyumjev U-100 Insulin

ACTIVE COMPARATOR

Participants will receive 0.20 u/kg commercially available U-100 Lyumjev insulin (unmodified) through subcutaneous injection.

Drug: Lyumjev U-100 Insulin; Dietary Supplement: Boost Mixed Meal Test

Interventions

Lyumjev U-100 Insulin DRUG

Commercially available U-100 Lyumjev (insulin lispro-aabc) administered unmodified as comparator. Administered as single subcutaneous injection at 0.20 u/kg body weight following mixed meal consumption.

Lyumjev U-100 Insulin

Boost Mixed Meal Test DIETARY_SUPPLEMENT

Standardized mixed meal (Boost drink) administered at 8.0 mL/kg body weight (17.3 g carbohydrates per 100 mL) consumed immediately before insulin injection at each visit.

Diluted Humalog U-200 Insulin; Diluted Humulin U-500 Insulin; Lyumjev U-100 Insulin

Diluted Humalog U-200 Insulin DRUG

Commercially available U-200 Humalog (insulin lispro) diluted 1:1 with a dilution buffer composed of sterile water, EDTA and mannitol to achieve U-100 concentration. Administered as single subcutaneous injection at 0.20 u/kg body weight following mixed meal consumption.

Diluted Humalog U-200 Insulin

Diluted U-500 Humulin Insulin DRUG

Commercially available U-500 Humulin (regular insulin) diluted 1:4 with dilution buffer composed of sterile water, EDTA and mannitol to achieve U-100 concentration. Administered as single subcutaneous injection at 0.20 u/kg body weight following mixed meal consumption.

Diluted Humulin U-500 Insulin

Eligibility Criteria

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

You may qualify if:

• To be eligible for the study, a subject must meet all of the following criteria:
• years of age
• Clinical diagnosis of type 1 diabetes
• On insulin pump therapy and continuous glucose monitor for at least 3 months
• For females of childbearing potential, a negative pregnancy test and not attempting to conceive.
• Understanding and willingness to follow the protocol and sign informed consent
• Ability to speak, read and write English

You may not qualify if:

• Diabetic ketoacidosis within 3 months
• Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
• Have donated blood within 8 weeks
• Have a known clinically significant history of anemia
• Pregnant or lactating
• Active infection
• Any medical condition that, in the investigator's opinion, might interfere with study completion or participant safety.
• Known seizure disorder
• Inpatient psychiatric treatment within 6 months
• Medication instability within 1 month prior to enrollment, including antihypertensive, thyroid, antidepressant, or lipid-lowering medications
• Suspected drug or alcohol abuse
• Chronic kidney disease (GFR \< 60 mL/min/1.73m²)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

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

Study Officials

• Rayhan A Lal, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Eric Appel, PhD

  Stanford University

  STUDY DIRECTOR

Central Study Contacts

Ryan Kingman, BS

CONTACT

650-736-4417; rkingman@stanford.edu

Alex Prossnitz, PhD

CONTACT

562-370-8779; apross@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine & Pediatrics

Model Details: Randomized, three-period, three-treatment crossover study. Each participant will receive all three insulin formulations (diluted U-200 Humalog, diluted U-500 Humulin, and U-100 Lyumjev) in randomized sequence across three separate visits.

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: July 29, 2025
• Study Start: October 28, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available beginning 18 months after article publication and ending 5 years following article publication.
• Access Criteria: Proposals should be directed to eappel@stanford.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)