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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01600950

Enrollment

Registered

2012-05-17

Start date

2012-05-31

Completion date

2012-07-31

Last updated

2014-10-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1

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.

Interventions

DRUGLY2963016

Single 0.3 U/kg dose administered subcutaneously

DRUGLantus

Single 0.3 U/kg dose administered subcutaneously

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.

Countries

Germany

Participant flow

Pre-assignment details

This was a randomized, 2-period, 2-sequence, crossover study.

Participants by arm

Arm	Count
All Participants A single 0.3 units/kilogram (U/kg) dose of either LY2963016 or LANTUS was administered subcutaneously on Day 1 of Periods 1 or 2.	20
Total	20

Baseline characteristics

Characteristic	All Participants
Age, Continuous	41.5 years STANDARD_DEVIATION 9.1
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	20 Participants
Region of Enrollment Germany	20 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	4 / 20	3 / 20
serious Total, serious adverse events	0 / 20	0 / 20

Outcome results

Primary

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.