Suppression of Endogenous Glucose Production by Injectable HDV-Insulin Lispro: A Dose Response Study in Human Subjects With Type 1 Diabetes

NCT05689424 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: DP 01-2022-02
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

Single-center, double-blind, random-sequence study assessing the HDV dose-response relationship to Endogenous Glucose Production (EGP), Free Fatty Acids (FFA) and Glucose Disposal Rate (GDR) during a euglycemic clamp procedure following overnight stabilization of blood glucose with intravenous insulin (and, if needed intravenous glucose). EGP and GDR will be determined using established radioisotope methodology. The concentration of Hepatic Directed Vesicles (HDV) in the insulin lispro (LIS) infused during the clamp procedure will be varied such that the percentage of HDV-bound LIS will range from 0%, 1%, 10%, and 100%. Each participant will thus undergo four clamp procedures at the four different HDV levels. LIS will be infused at a constant dose (6 mU/m2/min) for each of the four procedures.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Percentage of suppression of endogenous glucose production

  To establish the dose-response relationship between Hepatic-Directed Vesicles (HDV) and endogenous glucose production at a constant dose of insulin lispro (LIS) during euglycemic clamp procedure

  0 through 6 hours

Study Arms (4)

HDV-bound Lispro 0%

PLACEBO COMPARATOR

Subjects will receive insulin lispro with 0% bound HDV

Drug: HDV-Insulin Lispro

HDV-bound Lispro 1%

ACTIVE COMPARATOR

Subjects will receive insulin lispro with 1% bound HDV

Drug: HDV-Insulin Lispro

HDV-bound Lispro 10%

ACTIVE COMPARATOR

Subjects will receive insulin lispro with 10% bound HDV

Drug: HDV-Insulin Lispro

HDV-bound Lispro 100%

ACTIVE COMPARATOR

Subjects will receive insulin lispro with 100% bound HDV

Drug: HDV-Insulin Lispro

Interventions

HDV-Insulin Lispro DRUG

The name of the investigational drug is Hepatic Directed Vesicles + Insulin Lispro (HDV-bound LIS). It is a nano-carrier-based formulation of insulin which is the active therapeutic ingredient in the product. The nano-carrier component of the formulation contains a hepatic target molecule, biotin phosphatidylethanolamine, which has an affinity for hepatocytes and enables the product to deliver insulin directly to the liver.

HDV-bound Lispro 0%; HDV-bound Lispro 1%; HDV-bound Lispro 10%; HDV-bound Lispro 100%

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female of age 18 to 65 years, inclusive, who:
• Has at Screening been diagnosed as T1D for at least 12 months; preference will be given to potential participants who currently use continuous subcutaneous insulin infusion (CSII) therapy;
• Has at Screening C-peptide ≤0.8 ng/mL (single retest allowed);
• Has at Screening a BMI ≥18.0 kg/m2 and ≤33.0 kg/m2;
• Has at Screening HbA1c ≥6.5% and ≤8.5 %.

You may not qualify if:

• Has known or suspected allergy to any component of any of the study drugs in this trial;
• Is, at Screening, pregnant or breast-feeding, or intends to become pregnant at any time during the duration of the study;
• Has, at Screening, as judged by the Site Investigator, a history or current evidence of any of advance complications of diabetes;
• Is, at Screening, judged by the Site Investigator to have a current addiction to alcohol or substances of abuse;
• Is, at Screening, using one or more drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia (e.g., beta blockers, systemic corticosteroids at pharmacologic doses, cancer chemotherapies);
• Has, within one (1) month prior to Screening, used either oral anti-diabetic medication or noninsulin anti-diabetic injection therapies (e.g. SGLT-2 inhibitors, pramlintide, GLP-1 agonists, etc.);
• Has, within one (1) month prior to Screening, received any investigational drug;
• Has, within three (3) months prior to Screening, smoked tobacco or used any smokeless tobacco or nicotine delivery system (inhaled, oral or buccal);
• Has at Screening, as judged by the Site Investigator, any condition (intrinsic or extrinsic) that could reasonably be expected to interfere with trial participation, confound evaluation of the data, or pose additional risk to adhering to the study protocol. Examples of such conditions include but are not limited to:
• Clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurological, renal, genitourinary, or hematological systems;
• History of such an illness or disease;
• Diminished mental capacity, psychological or behavioral dysfunction, unwilling or resistant to protocol requirements, language barriers.

Sponsors & Collaborators

• University of California, San Diego: lead
• The Leona M. and Harry B. Helmsley Charitable Trust: collaborator

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Todd May, MS

CONTACT

858-246-2169; tmay@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: January 19, 2023
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share