Study of LY2409021 in Participants With Type 1 Diabetes

Study Overview
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Brief Summary
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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.

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

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: LY2409021
* Drug: Placebo
* Drug: Glucagon


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 mg LY2409021<br>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: LY2409021<br>* Administered orally<br>Drug: Placebo<br>* Administered orally<br>Drug: Glucagon<br>* Administered via intramuscular injection<br>|
| Experimental: 300 mg LY2409021<br>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<br>* Administered orally<br>Drug: Glucagon<br>* Administered via intramuscular injection<br>|
| Placebo Comparator: Placebo<br>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<br>* Administered orally<br>Drug: Glucagon<br>* Administered via intramuscular injection<br>|

What is the study measuring?
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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 |