Clinical trial NCT01784211: A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes
Official title: The Pharmacokinetic and Pharmacodynamic Intra-subject Variability of LY2605541 and the Effect of Exercise on LY2605541 Pharmacokinetics in Patients With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-02-05
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to measure how much of the study drug or insulin glargine gets into the blood stream and how long it takes the body to get rid of it. The effect of exercise will also be evaluated.

This study has two parts. In Part A, each participant will receive a daily injection of LY2605541 or insulin glargine for about 15 days. Some participants may continue into Part B. In Part B, participants will receive a daily injection of LY2605541 or insulin glargine with or without exercise. Part B lasts about 6 days.

Participants will remain on their regular physician-prescribed mealtime insulin throughout the study.


Eligibility criteria: Inclusion Criteria:

* Are males or females that have had a diagnosis of Type I Diabetes Mellitus (T1DM) for at least 12 months and are receiving multiple daily insulin injections. Total daily insulin dose \<1.2 units per kilogram per day (U/kg/day); daily basal dose \>0.2 U/kg/day
* Female participants: are women of child-bearing potential who test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control during the study
* Have a body mass index (BMI) of 18 to 30 kilograms per meter squared (kg/m\^2), inclusive
* Have a fasting c-peptide \<0.3 nanomoles per liter (nmol/L)
* Have a hemoglobin A1c (HbA1c) \<9% at screening

Participants with T1DM are eligible for enrollment in Part B of the study only if they meet all of the following criteria:

* Have a maximal oxygen uptake (VO2 max) of ≥25 milliliters (mL) of oxygen per kilogram per minute (O2/kg/min) (for women) or ≥30 mL O2/kg/min (for men)
* Perform regular physical cardiorespiratory activity to achieve an average total energy expenditure of ≥500 metabolic equivalent of task (MET)-minutes per week during the last 3 months prior to screening

Exclusion Criteria:

* Have known allergies to LY2605541, insulin glargine, related compounds or any components of the formulation
* Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from 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
* Have had episodes of severe hypoglycemia in the past 6 months (severe hypoglycemia is defined as having neurological symptoms consistent with neuroglycopenia and having required assistance in treatment by a second party)
* Have a history of hypoglycemia unawareness
* Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that may affect blood glucose, the body's sensitivity to insulin, or that promote weight loss within 14 days prior to dosing
* Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to comply with study requirements regarding alcohol consumption
* Currently smokes \>5 cigarettes per day, or are unwilling to comply with study requirements regarding smoking or use of tobacco products
* Have a hemoglobin level \<8.0 millimoles per liter (mmol/L) (male) or \<6.4 mmol/L (female) at screening
* Are currently participating in a weight loss program or plan to do so during the course of the study
* Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, and intra-ocular preparations) or have received such therapy within the 4 weeks before dosing
* Have fasting triglycerides \>400 milligrams per deciliter (mg/dL) (4.52 mmol/L)
* Have previous history or family history of deep vein thrombosis

Primary outcomes:
measure: Part A: Pharmacokinetics: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCτ) of LY2605541 and Insulin Glargine: Intra-Participant Variability
timeFrame: Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14
measure: Part A: Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2605541 and Insulin Glargine: Intra-Participant Variability
timeFrame: Part A: Predose and 4, 8, 12, and 24 hours postdose on Days 8, 11, and 14
Secondary outcomes:
measure: Part A: Pharmacodynamics: Total Amount of Glucose Infused Over the Duration of the Clamp (Gtot): Intra-Participant Variability
timeFrame: Part A: Predose up to 24 hours postdose on Days 8, 11, and 14
measure: Part B: Pharmacokinetics: AUCτ of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise
timeFrame: Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19
measure: Part B: Pharmacokinetics: Cmax of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise
timeFrame: Part B: Predose, 11 hours postdose, every 30 minutes from 16.5 to 20 hours postdose, and 24 hours postdose on Day 16 or 19
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: