A Study of Multiple Increasing Doses of LY2409021 in Participants With Type 2 Diabetes

The Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Multiple Escalating Doses of LY2409021 in Patients With Type 2 Diabetes Mellitus

The study drug LY2409021 is being evaluated as a possible treatment for diabetes. The primary purpose of this study is to help answer the following research questions, and not to provide treatment for diabetes :

• The safety of LY2409021 and any side effects that might be associated with it following 4 weeks of doses
• How long it takes the body to absorb and remove LY2409021 following dosing over 4 weeks
• How daily dosing of LY2409021 affects blood levels of sugar (glucose), insulin and other naturally occurring substances before and after a meal
• How LY2409021 works when given with metformin
• How daily dosing of LY2409021 affects the cells that produce insulin

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 50
• 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.
• United Kingdom
  • Plymouth, United Kingdom
    • 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 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be either a male, or a female who cannot become pregnant, who has type 2 diabetes and is either controlling diabetes through diet and exercise, or taking metformin
• Have an hemoglobin A1c (HbA1c) value at screening of greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen at the time of measurement
• Have a screening body mass index (BMI) of 20 to 40 kg/m^2 inclusive
• Have a blood pressure reading at screening of between 90 to 160 millimeters of mercury (mmHg) (systolic) and 40 to 95 mmHg (diastolic)

Exclusion Criteria:

• Have used insulin for diabetic control within 1 year of study entry
• Have used thiazolidinediones within 3 months, or any other drugs for treatment of hyperglycemia (except metformin) within 1 month, prior to first planned dosing. Metformin is acceptable for this study.
• Have clinically significant coronary artery disease
• Have clinically significant peripheral vascular disease
• Have clinical evidence of active diabetic proliferative retinopathy
• Have known significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis
• Impaired renal function (serum creatinine greater than 115 micromoles/liter [μmol/L] [1.3 mg/dL] in women, greater than 130 μmol/L [1.5 mg/dL] in men)
• Have triglycerides greater than 4.5 millimoles per liter (mmol/L) [approximately 400 mg/dL] at screening
• Were hospitalized for poor control of diabetes (keto-acidotic episode) in the last 6 months
• Are allergic to LY2409021 or similar drugs
• Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data
• Have used systemic glucocorticoids within 1 month prior to first dosing
• Have donated 450 mL or more of blood in the last 3 months or have donated any blood within 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered orally once daily for 4 weeks	Drug: Placebo; Administered orally (capsule)
Experimental: 5 mg LY2409021; 5 mg LY2409021 administered orally once daily for 4 weeks	Drug: LY2409021; Administered orally (capsule)
Experimental: 30 mg LY2409021; 30 mg LY2409021 administered orally once daily for 4 weeks	Drug: LY2409021; Administered orally (capsule)
Experimental: 60 mg LY2409021; 60 mg LY2409021 administered orally once daily for 4 weeks	Drug: LY2409021; Administered orally (capsule)
Experimental: 90 mg LY2409021; 90 mg LY2409021 administered orally once daily for 4 weeks	Drug: LY2409021; Administered orally (capsule)

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 28 days after last dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Area under the concentration curve (AUC) of LY2409021	From first study drug dose to Day 28 post last dose
Pharmacokinetics: Maximum concentration (Cmax) of LY2409021	From first study drug dose to Day 28 post last dose
Change in fasting blood glucose level	From Day -1 to Day 28 of dosing
Change in incremental area under the curve (AUC) for glucose	From Day -1 to Day 28 of dosing
Change in homeostasis model assessment of beta cell function (HOMA-B)	From baseline to Day 28
Change in fasting glucagon level	From Day -1 to Day 28 of dosing
Change in fasting insulin level	From Day -1 to Day 28 of dosing
Change in fasting C-peptide level	From Day -1 to Day 28 of dosing
Change in fasting glucagon-like peptide-1 (GLP-1) level	From Day -1 to Day 28 of dosing

Collaborators and Investigators

• Sponsor: 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: March 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

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: 11071 (DAIDS ES Registry Number); I1R-FW-GLBB (Other Identifier: Eli Lilly and Company)