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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: LY2409021

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • 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: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-45 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Kelly RP, Garhyan P, Raddad E, Fu H, Lim CN, Prince MJ, Pinaire JA, Loh MT, Deeg MA. Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes. Diabetes Obes Metab. 2015 Apr;17(4):414-22. doi: 10.1111/dom.12446. Epub 2015 Mar 2.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 23, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Estimate): May 25, 2012
• Last Update Submitted That Met QC Criteria: May 23, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 10837; I1R-FW-GLBA (Other Identifier: Eli Lilly and Company)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No