A Study To Compare the Effects of Insulin Peglispro and Glargine on Insulin Sensitivity and Meal Time Insulin Requirements in Type 2 Diabetics

NCT02197520 | Completed Phase 1 Results

• 2 other identifiers: 15407I2R-MC-BIDV
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will look into insulin sensitivity (how the body responds to insulin) and effects of meals on type 2 diabetics comparing insulin peglispro to insulin glargine. The study has two treatment periods, each of which will last about four weeks. One drug (insulin peglispro or insulin glargine) will be administered in each period. Participants will receive both drugs during the study. Participants may remain on stable dose metformin, as prescribed by their personal physician.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)

  During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.

  Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp

Secondary Outcomes (5)

• Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro

  Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast

• Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro

  Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast

• Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen

  Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast

• Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29

  Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast

• Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp

  Day 33 during euglycemic 2-step hyperinsulinemic clamp

Study Arms (2)

Insulin Peglispro (with Insulin Lispro)

EXPERIMENTAL

Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks

Drug: Insulin Peglispro; Drug: Insulin Lispro

Insulin Glargine (with Insulin Lispro)

ACTIVE COMPARATOR

Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks

Drug: Insulin Glargine; Drug: Insulin Lispro

Interventions

Insulin Peglispro DRUG

Administered subcutaneously (SC), (U-100 formulation)

Also known as: LY2605541

Insulin Peglispro (with Insulin Lispro)

Insulin Glargine DRUG

Administered subcutaneously (SC), (U-100 formulation)

Insulin Glargine (with Insulin Lispro)

Insulin Lispro DRUG

Administered subcutaneously (SC), (U-100 formulation)

Insulin Glargine (with Insulin Lispro); Insulin Peglispro (with Insulin Lispro)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable glycated hemoglobin (HbA1c) less than (\<) 10.0 percent (%)
• Stable dose of either 0.2 to 1.5 units per kilogram per day (U/kg/day) basal insulin or a total daily insulin dose l\<2.0 units per kilogram (U/kg)
• C-peptide \<0.3 nanomole per liter (nmol/L)
• Stable body during the last 2 months

You may not qualify if:

• Corrected QT interval (QTc) prolongation greater than (\>) 500 milliseconds (ms) or have any other abnormality in the 12 lead
• Abnormal blood pressure
• A history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus (T1DM)), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• Currently treated with oral antidiabetic drugs (OADs) (excluding metformin and dipeptidyl peptidase-4 (DPP4) inhibitors), or glucagon-like peptide-1 (GLP-1) agonists or intend to use over-the counter or prescription medication, herbal medications, or nutritional supplements that affect PG or insulin sensitivity, impact on hypoglycemic awareness or promote weight loss within 4 weeks prior to randomization
• Fasting triglycerides (TGs) \>400 milligrams per deciliter (mg/dL) (4.52 millimoles per liter (mmol/L))
• Have used systemic or inhaled corticosteroids/glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) within 4 weeks prior to randomization
• Currently receive insulin by pump or insulin degludec
• Poorly controlled diabetes or known to have poor awareness of hypoglycemia
• History of gastroparesis or gastrointestinal malabsorption
• Require treatment with any drug other than insulin to treat diabetes
• Previous history of proliferative retinopathy
• Excessive consumers of xanthines

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Profil Institute for Clinical Research Inc

Chula Vista, California, 91911, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

basal insulin peglispro; LY2605541; Insulin Glargine; Insulin Lispro

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 22, 2014
• Study Start: July 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: November 1, 2018
• Results First Posted: November 1, 2018

Record last verified: 2018-10

Locations

US (1)