A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01784211
First received: February 1, 2013
Last updated: November 27, 2013
Last verified: November 2013
  Purpose

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 meal time insulin throughout the study.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: LY2605541
Drug: Insulin Glargine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Part A: Pharmacokinetics: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCτ) of LY2605541 and Insulin Glargine: Intra-Participant Variability [ Time Frame: Part A: Predose up to Day 15 ] [ Designated as safety issue: No ]
  • Part A: Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2605541 and Insulin Glargine: Intra-Participant Variability [ Time Frame: Part A: Predose up to Day 15 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A: Pharmacodynamics: Total Amount of Glucose Infused Over the Duration of the Clamp (Gtot): Intra-Participant Variability [ Time Frame: Part A: Predose up to Day 15 ] [ Designated as safety issue: No ]
  • Part B: Pharmacokinetics: AUCτ of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise [ Time Frame: Part B: Day 17 to 21 ] [ Designated as safety issue: No ]
  • Part B: Pharmacokinetics: Cmax of LY2605541 and Insulin Glargine: Exercise Versus Non-Exercise [ Time Frame: Part B: Day 17 to 21 ] [ Designated as safety issue: No ]

Estimated Enrollment: 76
Study Start Date: February 2013
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2605541 (Part A)
0.5 units per kilogram (U/kg) LY2605541 subcutaneously (SQ) once daily for 15 days. Participants will remain on their regular physician-prescribed mealtime insulin. Part A involves 3 clamp procedures on Days 8, 11 and 14.
Drug: LY2605541
Administered SQ
Active Comparator: Glargine (Part A)
0.5 U/kg insulin glargine SQ once daily for 15 days. Participants will remain on their regular physician-prescribed mealtime insulin. Part A involves 3 clamp procedures on Days 8, 11 and 14.
Drug: Insulin Glargine
Administered SQ
Experimental: LY2605541 + Exercise (Part B)
0.5 U/kg LY2605541 SQ once daily for 6 days. Exercise challenge on Day 17 or 20. Participants will remain on their regular physician-prescribed mealtime insulin.
Drug: LY2605541
Administered SQ
Experimental: LY2605541 (Part B)
0.5 U/kg LY2605541 SQ once daily for 6 days. Participants will remain on their regular physician-prescribed mealtime insulin.
Drug: LY2605541
Administered SQ
Active Comparator: Glargine + Exercise (Part B)
0.5 U/kg insulin glargine SQ once daily for 6 days. Exercise challenge on Day 17 or 20. Participants will remain on regular physician-prescribed mealtime insulin.
Drug: Insulin Glargine
Administered SQ
Active Comparator: Glargine (Part B)
0.5 U/kg insulin glargine SQ once daily for 6 days. Participants will remain on regular physician-prescribed mealtime insulin.
Drug: Insulin Glargine
Administered SQ

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Are males or females that have had a diagnosis of Type I Diabetes Mellitis (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 square (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 type 1 diabetes), 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 or 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 intraocular 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01784211

Locations
Germany
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.
Neuss, Germany
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01784211     History of Changes
Other Study ID Numbers: 14183, I2R-MC-BIAW
Study First Received: February 1, 2013
Last Updated: November 27, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Glargine
Insulin
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014