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

Phase 1

Completed

Conditions: Diabetes Mellitus, Type 1

Interventions: Drug: LY2963016
Drug: Lantus

Registration Number: NCT01600950

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LY2963016	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.
Lantus	Lantus	A single 0.3 U/kg dose of Lantus will be administered subcutaneously followed by a minimum washout period of 7 days.

Primary Outcome Measures

Name	Time	Method
Pharmacodynamics: Duration of Action of LY2963016 and Lantus	Periods 1 and 2: Baseline up to 42 hours postdose	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2963016 and Lantus	Periods 1 and 2: Baseline up to 42 hours postdose	AUC was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay.
Maximum Glucose Infusion Rate (Rmax)	Periods 1 and 2: Baseline up to 42 hours postdose	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.
Total Glucose Infused (Gtot)	Periods 1 and 2: Baseline up to 42 hours postdose	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.
Time of Maximum Glucose Infusion Rate (tRmax)	Periods 1 and 2: Baseline up to 42 hours postdose	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.
Pharmacokinetics: Maximum Concentration (Cmax) of LY2963016 and Lantus	Periods 1 and 2: Baseline up to 42 hours postdose	Cmax was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay.

Trial Locations

Locations (1): 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.
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Neuss, Germany