Comparison of Different Insulin Dosing Algorithms Using Hepatic Directed Vesicle-Insulin Lispro and Insulin Degludec

• ClinicalTrials.gov Identifier: NCT03938740
• Recruitment Status: Completed
• First Posted: May 6, 2019
• Last Update Posted: April 2, 2020
• Sponsor: Diasome Pharmaceuticals
• Information provided by (Responsible Party): Diasome Pharmaceuticals

Study Description

Brief Summary:

Multi-center, open-label, multiple dose safety, tolerability and efficacy study

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: HDV-Insulin Lispro and Insulin Degludec (-40%); Drug: HDV-Insulin Lispro and Insulin Degludec (-10%)	Phase 2

Detailed Description:

This is a 24-week, open-label, multiple dose safety, tolerability and efficacy study. There is a 12-week run-in phase when all subjects receive Insulin Lispro and Insulin Degludec for 12 weeks. After completing the run-in period, subjects then are randomized to a treatment group of either HDV- Insulin lispro + Insulin Degludec (Degludec dose reduced by 40%) or HDV-Insulin lispro+ Insulin Degludec (Degludec dose reduced by 10%) for 12 weeks of treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Exploratory Randomized Open-Label 2-Arm Comparison of Insulin Dosing Algorithms Using Hepatic Directed Vesicle-Insulin Lispro and Insulin Degludec to Determine Optimum Basal Insulin Dosing Regimens in Type 1 Diabetes Mellitus Subjects
• Actual Study Start Date: March 18, 2019
• Actual Primary Completion Date: December 6, 2019
• Actual Study Completion Date: March 18, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: HDV-Insulin Lispro and Insulin Degludec dose reduced by 40%; HDV-Insulin Lispro and Insulin Degludec dose reduced by 40%	Drug: HDV-Insulin Lispro and Insulin Degludec (-40%); HDV-Insulin Lispro and Insulin Degludec (-40%)
Experimental: HDV-Insulin Lispro and Insulin Degludec dose reduced by 10%; HDV-Insulin Lispro and Insulin Degludec dose reduced by 10%	Drug: HDV-Insulin Lispro and Insulin Degludec (-10%); HDV-Insulin Lispro and Insulin Degludec (-10%)

Outcome Measures

Primary Outcome Measures :

1. Basal, bolus and total insulin doses (UOM=units) during the last 2 weeks of the treatment period [ Time Frame: 24 weeks ]
   Basal, bolus and total insulin doses (UOM=units) during the last 2 weeks of the treatment period
2. Basal/bolus ratios during the last 2 weeks of the treatment period [ Time Frame: 24 weeks ]
   Basal/bolus ratios during the last 2 weeks of the treatment period

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female of age 18 to 65 years, inclusive.
2. If female of child-bearing potential, must agree for the duration of the study. to use adequate contraceptive measures, such as, intra-uterine device [IUD], oral or injectable contraceptives, or barrier method plus spermicide.
3. Has at Screening been diagnosed as T1DM for at least 12 months.
4. Has at Screening C-peptide ≤0.8 ng/mL (single retest allowed).
5. Has at Screening been on treatment with rapid analog insulin for the previous six (6) months.
6. Has at Screening willingness to use continuous glucose monitoring (CGM) technology throughout study.
7. Is, for the duration of the study, willing to use insulin lispro as the only analog bolus insulin and insulin degludec as the only basal insulin.
8. Has at Screening a BMI ≥18.0 kg/m2 and ≤33.0 kg/m2.
9. Has at Screening HbA1c ≥6.5% and ≤8.5%.

Exclusion Criteria:

1. Has known or suspected allergy to any component of any of the study drugs in this trial.
2. Is, at Screening, pregnant or breast-feeding, or intends to become pregnant at any time during the duration of the study.
3. Has, at Screening, as judged by the Site Investigator, a history or current evidence of any of the following complications of diabetes: proliferative retinopathy or maculopathy, severe neuropathy (in particular, autonomic neuropathy), symptomatic gastroparesis.
4. Is, at Screening, judged by the Site Investigator to have a current addiction to alcohol or substances of abuse.
5. 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.).

6. Has at Screening any of the following findings, unless approved by both the Site Investigator and the Medical Monitor:

   • Uncontrolled hypertension, defined as diastolic blood pressure ≥ 100 mmHg and/or systolic blood pressure ≥ 160 mmHg after 5 minutes in the sitting position;
   • History of or findings on EKG of cardiac arrhythmia or conduction defect;
   • Clinically significant abnormalities on Screening laboratory studies
7. Has, within one (1) month prior to Screening, used either oral anti-diabetic medication or non-insulin anti-diabetic injection therapies (e.g. SGLT-2 inhibitors, pramlintide, GLP-1 agonists, etc.).
8. Has, within one (1) month prior to Screening, received any investigational drug.
9. Has, within two (2) months prior to Screening, used an insulin pump delivery system.
10. Has, within three (3) months prior to Screening, smoked tobacco or used any smokeless tobacco or nicotine delivery system (inhaled, oral or buccal).

11. 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

Contacts and Locations

Locations

United States, California

Mills-Peninsula Medical Center, Diabetes Research Institute

San Mateo, California, United States, 94401

United States, Colorado

Barbara Davis Center for Diabetes

Aurora, Colorado, United States, 80045

United States, Georgia

Atlanta Diabetes Associates

Atlanta, Georgia, United States, 30318

Endocrine Research Solutions, Inc.

Roswell, Georgia, United States, 30076

United States, North Carolina

Diabetes & Endocrinology Consultants, PC

Morehead City, North Carolina, United States, 28557

United States, Texas

Texas Diabetes & Endocrinology, PA

Austin, Texas, United States, 78749

Texas Diabetes & Endocrinology, PA

Round Rock, Texas, United States, 78681

Sponsors and Collaborators

Diasome Pharmaceuticals

Investigators

• Study Director: Marc Penn, MD, PhD; Diasome Pharmaceuticals

More Information

• Responsible Party: Diasome Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03938740
• Other Study ID Numbers: DP 01-2019-01
• First Posted: May 6, 2019
• Last Update Posted: April 2, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Insulin Lispro; Insulin, Long-Acting; Hypoglycemic Agents; Physiological Effects of Drugs