A Study of LY2922083 in Healthy Participants and Participants With Diabetes

Study Overview
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Brief Summary
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The aim of this trial is to evaluate the safety of the study drug in healthy participants and participants with diabetes. It will investigate how much of the study drug gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected. The study consists of two parts. Part A will study healthy participants in up to 3 dosing periods over approximately 6 weeks. Part B will study participants with diabetes in up to 3 dosing periods over approximately 6 weeks.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Oral Doses of LY2922083 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: LY2922083


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all participants : Must be a male, or a female who cannot become pregnant, and who is either a healthy participant, or who has type 2 diabetes Have a screening body mass index (BMI) of at least 18.0 kilograms per square meter (kg/m^2) Have blood pressure, pulse rate, blood and urine laboratory test results acceptable for the study For participants with T2DM: Do not have any change to their diabetes treatment (exercise with or without metformin) for at least 4 weeks prior to screening Have a glycated hemoglobin (HbA1c) value of greater than or equal to 6% and less than or equal to 11% at screening Exclusion Criteria: For all participants : Are currently participating in another clinical study or completed one in the last 30 days Are allergic to LY2922083 or other related drugs 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 electrocardiogram (ECG) readings that are not suitable for the study Have a history of hepatitis or jaundice Are infected with hepatitis B Are infected with hepatitis C Are infected with human immunodeficiency virus (HIV) Have donated more than 450 milliliters (mL) of blood in the last 3 months or have donated any blood in the last month 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) Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic For participants with T2DM : Have had heart disease or stroke within 6 months before entering the study Have health complications due to poorly controlled diabetes as shown by blood and urine laboratory test results or based on physical examination and medical assessment as determined by the study doctor Have been hospitalized for poor control of diabetes (keto-acidotic episode) in the last 6 months Have used insulin to control diabetes in the last 1 year Show symptoms of high blood sugar (for example, frequent urination, always feeling thirsty, or unexpected weight loss)

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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No

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Part A)<br>Single oral dose of placebo administered to healthy participants in up to 1 of 3 study periods in Part A | Drug: Placebo<br>* Administered orally as capsules<br>|
| Experimental: LY2922083 (Part A)<br>Single ascending dose of LY2922083 (starting at 0.5 milligrams [mg]) administered orally to healthy participants in up to 2 of 3 study periods in Part A | Drug: LY2922083<br>* Administered orally as capsules<br>|
| Placebo Comparator: Placebo (Part B)<br>Single oral dose of placebo administered to participants with type 2 diabetes mellitus (T2DM) in up to 1 of 3 study periods in Part B | Drug: Placebo<br>* Administered orally as capsules<br>|
| Experimental: LY2922083 (Part B)<br>Single ascending dose of LY2922083 administered orally to participants with T2DM in up to 2 of 3 study periods in Part B. Dose determined by Part A | Drug: LY2922083<br>* Administered orally as capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | Events deemed by the Investigator to be SAEs related to study drug administration are reported. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Baseline through study completion (up to 70 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 |  | Predose up to 72 hours (h) after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.) | 
| PK: Maximum Concentration (Cmax) of LY2922083 |  | Predose up to 72 h after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.) | 
| Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | Least Squares (LS) mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error. | Baseline (predose for Part A and Day -1 time-matched for Part B), up to 24 h postdose (1.5, 2.5, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, and 24 h postdose) | 
| Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | LS mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error. | Baseline (predose for Part A and Day -1 time-matched for Part B), up to 6 h postdose (1.5, 2.5, 4, 4.5, 5, and 6 h postdose) |