Study of LY2409021 in Participants With Type 1 Diabetes

Pilot Study of the Effects of LY2409021 in Patients With Type 1 Diabetes Mellitus

This study involves taking a single dose of 100 milligrams (mg) or 300 mg LY2409021 or placebo (an inactive medicine) taken as up to 3 capsules by mouth. The study will evaluate if this drug will reduce the amount of insulin a type 1 diabetic needs over 24 hours. This study includes a 7-day hospitalization period at the clinical research unit (CRU) and will involve screening within 30 days of the start of the study as well as telephone consultations within 5 days after discharge from the CRU.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Placebo; Drug: LY2409021; Drug: Glucagon

• 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 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have had type 1 diabetes mellitus (T1DM) based on the World Health Organization classification for at least 1 year and have a daily insulin dose ≤1.5 international units (IU) per kilogram (kg) of body weight
• Have a glycated hemoglobin A1c (HbA1c) of no greater than 9.0% as measured at screening
• Have a body mass index (BMI) ≥19.0 and ≤35.0 kilograms per meter squared (kg/m^2)
• Have given written informed consent approved by Lilly

Exclusion Criteria:

• Received any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 3 months prior to screening
• Have had more than 1 episode of severe hypoglycemia within 3 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness
• Are pregnant or intend to become pregnant during the course of the study
• Women who are breastfeeding
• Have a history of stroke, myocardial infarction, heart failure, unstable angina, or a coronary revascularization procedure within 6 months of screening
• Have fasting triglycerides >500 milligrams per deciliter (mg/dL) (5.65 millimoles per liter [mmol/L])
• Have obvious clinical signs, symptoms, or laboratory evidence of liver disease (alanine transaminase [ALT] or aspartate transaminase [AST] greater than 2 times the upper limit of normal at screening)
• Have a history of renal transplantation or are currently receiving renal dialysis or have a screening creatinine >2.0 mg/dL (177 micromoles per liter [μmol/L])
• Have had any other disease, illness, or condition (including known diabetic autonomic neuropathy, drug or alcohol abuse, or psychiatric disorder) within the 6 months prior to screening that precludes the participant from following and completing the study or could increase their risk for hypoglycemia, according to the investigator's judgment
• Are currently enrolled in, have completed, or have discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 100 mg LY2409021; LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Drug: Placebo; Administered orally; Drug: LY2409021; Administered orally; Drug: Glucagon; Administered via intramuscular injection
EXPERIMENTAL: 300 mg LY2409021; LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.	Drug: LY2409021; Administered orally; Drug: Glucagon; Administered via intramuscular injection
PLACEBO_COMPARATOR: Placebo; Placebo: 3 capsules administered as a single oral dose on Day 2. Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3.	Drug: Placebo; Administered orally; Drug: Glucagon; Administered via intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose	The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.	Baseline (Day 1), Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin	The percentage change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.	Baseline (Day 1), Day 2
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021		Predose (Day 2) through 120 hours postdose (Day 7)
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021	Exposure in terms of AUC of LY2409021 from time 0 extrapolated to infinity (AUCinf) is reported.	Predose (Day 2) through 120 hours postdose (Day 7)
Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose During Drug Washout Period	Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.	Baseline (Day 1), Day 3 up to Day 6
Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose Needed to Maintain Euglycemia	Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.	Baseline (Day 1), Day 3 up to Day 6
Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3	The Cmax of glucose following a single dose of glucagon (1 mg) administered via an intramuscular injection is reported.	Day 3
Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3	Area under the glucose concentration curve from time 0 through 2 hours after a single dose of glucagon (1 milligram) administered via an intramuscular injection is reported.	Day 3

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 13, 2012
• First Posted (ESTIMATE): July 16, 2012

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2018
• Last Update Submitted That Met QC Criteria: March 24, 2018
• Last Verified: March 1, 2018

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; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: 14576; I1R-MC-GLBR (OTHER: Eli Lilly and Company); 2011-006178-19 (EUDRACT_NUMBER)