A First-in-Human Study of LY2409021 in Healthy Participants and Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety of LY2409021 in healthy participants and participants with diabetes. The study drug is given as single oral doses. Each participant can receive up to 3 doses, with a minimum 7 day washout between dosing periods. Side effects will be documented. This study is approximately 9 weeks long, not including screening. Screening is required within 6 weeks prior to the start of the study.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2409021 After Escalating Single Oral Dose Administration in Healthy Subjects and Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: LY2409021


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all participants: Must be either a male, or a female who cannot become pregnant, who is either healthy or have type 2 diabetes mellitus (T2DM) but not taking medication for diabetes Have an hemoglobin A1c (HbA1c) value of less than or equal to 10% at screening Have blood and urine laboratory test results that are acceptable for the study For healthy participants: Have a screening body mass index (BMI) of 18.5 to 29.9 kg/m^2 inclusive Have a fasting blood glucose between 3.0-5.2 millimoles/liter (mmol/L) at screening Have plasma glucose, two hours after ingesting an oral 75 g glucose load, less than 7.8 mmol/L For participants with type 2 diabetes mellitus (T2DM): Have a screening body mass index (BMI) of 18.5 to 35 kg/m^2 inclusive Must weigh 45 kg or more at screening Have a fasting blood glucose less than 11.1 mmol/L at screening Have plasma glucose, two hours after ingesting an oral 75 g glucose load, greater than or equal to 11.1 mmol/L Exclusion Criteria: For all participants: Have participated in a study with a new drug in the last 30 days Have a history of significant heart, lung, liver, kidney, stomach or brain disease, or have any medical problems which may cause an increased risk during the study Have hypertension requiring more than single-agent therapy, or blood pressure greater than 140/90 millimeters of mercury (mmHg) on monotherapy Are allergic to LY2409021 or similar drugs Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female), or are unwilling to stop alcohol as required by the study restrictions (1 unit = 360 mL of beer, or 150 mL of wine, or 45 mL of spirits) Intend to use other over-the-counter or prescribed medicines during 7 or 14 days respectively before the study, or during the study. Medicines for high cholesterol and high blood pressure are allowed if you have diabetes. Have a significant blood disorder and/or donated blood (450 ml or more) in the last 3 months For participants with T2DM: Have signs of having serious problems with diabetes (For example, severe eye problems, poorly healing skin) Have a history of being in a coma due to low blood sugar

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Healthy-Placebo<br>Placebo (capsule) administered once, orally | Drug: Placebo<br>* Administered orally<br>|
| Experimental: Healthy-2.5 mg LY2409021<br>2.5 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Healthy-10 mg LY2409021<br>10 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Healthy-30 mg LY2409021<br>30 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Healthy-100 mg LY2409021<br>100 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Healthy-250 mg LY2409021<br>250 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Healthy-500 mg LY2409021<br>500 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Placebo Comparator: Diabetic-Placebo<br>Placebo (capsule) administered once, orally | Drug: Placebo<br>* Administered orally<br>|
| Experimental: Diabetic-75 mg LY2409021<br>75 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Diabetic-200 mg LY2409021<br>200 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: Diabetic-500 mg LY2409021<br>500 mg LY2409021 administered once, orally | Drug: LY2409021<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with one or more drug related adverse events (AEs) or any serious AEs |  | From first dose of study drug up to discharge (at least 14 days after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area under the concentration curve (AUC) of LY2409021 |  | From each dose of study drug up to 14 days post dose | 
| Pharmacokinetics: Maximum concentration (Cmax) of LY2409021 |  | From each dose of study drug up to 14 days post dose | 
| Change in fasting blood glucose level |  | From each dose of study drug up to 48 hours post dose | 
| Change in fasting insulin level |  | From each dose of study drug up to 48 hours post dose | 
| Change in fasting glucagon level |  | From each dose of study drug up to 48 hours post dose | 
| Change in fasting glucagon-like peptide-1 (GLP-1) level |  | From each dose of study drug up to 24 hours post dose | 
| Glucose excursion after meals |  | 28 hours after each dose |