A Study to Compare LY2963016 to Lantus After a Single Dose to Participants With Type 1 Diabetes Mellitus

Pharmacodynamics of LY2963016 Compared to LANTUS® in Subjects With Type 1 Diabetes Mellitus

The study involves a single injection of LY2963016 and a single injection of Lantus, on 2 separate occasions in participants with type I diabetes. Following each dose, participants will undergo a glucose clamp which lasts for 42 hours each time. There will be at least 7 days between the two periods, during which time there will be no study treatment, but participants will resume their regular therapy. The duration of this study can be up to 9.5 weeks. The purposes of this study are to understand how the blood sugar lowering effect of LY2963016 compares to that of Lantus, and to determine how LY2963016 and Lantus are metabolized by participants with type I diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: LY2963016; Drug: Lantus

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• have type 1 diabetes mellitus (T1DM) based on the disease diagnostic criteria
• have had a duration of diabetes ≥1 year
• have hemoglobin A1c ≤10.0%
• have fasting C-peptide ≤0.3 nanomoles per liter (nmol/L)
• have a body mass index ≤29 kilograms per square meter (kg/m²)
• have venous access sufficient to allow blood sampling and cannulation for clamp procedures

Exclusion Criteria:

• are currently enrolled in, have completed, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device
• have a total insulin requirement >1.2 units per kilogram per day (U/kg/day)
• have a history of proliferative retinopathy
• have known allergies to insulin glargine, insulin lispro, heparin, or related compounds
• have an electrocardiogram (ECG) reading considered outside the normal limits
• have an abnormal blood pressure
• have abnormal clinical laboratory tests
• have a history or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
• history of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in first-degree relatives
• show evidence of significant active neuropsychiatric disease
• regular use of known drugs of abuse and/or show positive findings on drug screening
• show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
• show evidence of hepatitis C and/or positive hepatitis C antibody
• show evidence of hepatitis B and/or positive hepatitis B surface antigen
• are women with a positive pregnancy test or women who are lactating
• have an average weekly alcohol intake that exceeds 21 units per week (males) or 14 units per week (females)
• had more than 1 episode of severe hypoglycemia within 6 months prior to study
• undergoing therapy for a malignancy other than basal cell or squamous cell skin cancer
• had a blood transfusion or severe blood loss within 3 months; made a blood donation within 30 days prior to study entry; or have known hemoglobinopathy, haemolytic anemia, or sickle cell anemia
• are receiving systemic glucocorticoid therapy
• have irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night)
• show a history of adverse reactions to heparin, including heparin-induced thrombocytopenia
• smoke more than 10 cigarettes (or equivalent other tobacco products) per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2963016; A single 0.3 units per kilogram (U/kg) dose of LY2963016 will be administered subcutaneously followed by a minimum washout period of 7 days.	Drug: LY2963016; Single 0.3 U/kg dose administered subcutaneously
Active Comparator: Lantus; A single 0.3 U/kg dose of Lantus will be administered subcutaneously followed by a minimum washout period of 7 days.	Drug: Lantus; Single 0.3 U/kg dose administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: Duration of Action of LY2963016 and Lantus	Duration of action is defined as the period of time elapsed between dose administration and the time at which the participant's blood glucose is consistently >150 milligrams/deciliter (mg/dL) without any glucose infusion. Participants whose blood glucose did not rise to 150 mg/dL were censored 42 hours postdose.	Periods 1 and 2: Baseline up to 42 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Glucose Infusion Rate (Rmax)	Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain a target blood glucose level of 100 milligrams/deciliter (mg/dL) [5.6 millimoles/Liter (mmol/L)] and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate. Data presented are the maximum infusion rates, adjusted by body weight.	Periods 1 and 2: Baseline up to 42 hours postdose
Total Glucose Infused (Gtot)	Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate. Data presented are the total glucose infused, adjusted by body weight.	Periods 1 and 2: Baseline up to 42 hours postdose
Time of Maximum Glucose Infusion Rate (tRmax)	tRmax is the time to reach maximum glucose infusion rate and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate.	Periods 1 and 2: Baseline up to 42 hours postdose
Pharmacokinetics: Maximum Concentration (Cmax) of LY2963016 and Lantus	Cmax was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay.	Periods 1 and 2: Baseline up to 42 hours postdose
Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2963016 and Lantus	AUC was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay.	Periods 1 and 2: Baseline up to 42 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 15, 2012
• First Posted (Estimate): May 17, 2012

Study Record Updates

• Last Update Posted (Estimate): October 7, 2014
• Last Update Submitted That Met QC Criteria: October 3, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: 13831; I4L-MC-ABEE (Other Identifier: Eli Lilly and Company)