A Multiple-Ascending Dose Study in Type 2 Diabetes Mellitus Patients

Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Multiple Escalating Oral Doses of LY2393910 in Patients With Type 2 Diabetes Mellitus

The study drug LY2393910 is being evaluated as a possible treatment for diabetes. The primary purpose of a patient's participation in this study is to help answer the following research question(s), and not to provide treatment for diabetes:

• The safety of LY2393910 and any side effects that might be associated with it following 2 weeks of doses
• How long it takes the body to absorb and remove LY2393910 following dosing over 2 weeks
• How daily dosing of LY2393910 affects blood levels of sugar (glucose), insulin and other naturally occurring substances in your body
• How daily dosing of LY2393910 affects the cells that produce insulin
• Any differences in the above between LY2393910 taken as daily doses in the morning or in the evening

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: LY2393910; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, D-41460
    • 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:

• Diagnosis of type 2 diabetes mellitus
• Must be on a stable treatment regimen (maintained on diet/exercise therapy with or without metformin) for at least 4 weeks prior to study entry
• Have a glycated haemoglobin (HbA1c) value greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen
• Weigh 45.0 kg or more
• Have a Body Mass Index (BMI) greater than or equal to 18.5 and less than or equal to 40.0 kg/m2
• Are willing and able to conduct self-blood glucose monitoring tests

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving use of an investigational drug or device other than the study drug used in this study, or are concurrently enrolled in any other type of medical research judged not to be compatible with this study
• Use of insulin for diabetic control for more than 6 consecutive days within 1 year prior to study entry
• Use of thiazolidinediones within 3 months, or other oral anti-diabetics (OADs), apart from metformin, within 1 month prior to study entry. Metformin is acceptable for this study
• Previous myocardial infarction, stroke or transient ischaemic event ('TIA'), or clinically significant coronary events or symptoms within 6 months prior to study entry
• Subjects who have any evidence of heart insufficiency, hypokalaemia, family history of long-QT-syndrome or are receiving other drugs which extend the QT interval
• Clinically significant peripheral vascular disease
• Clinical evidence of active diabetic proliferative retinopathy
• Known significant autonomic neuropathy
• Any patient having experienced a keto-acidotic episode requiring hospitalisation in the last 6 months
• Symptomatic hyperglycemia exhibited by significant osmotic symptoms (polyuria or polydipsia), unanticipated weight loss or dehydration
• Evidence of hepatitis B and/or positive hepatitis B surface antigen, at screening
• Subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)
• Subjects who are heavy smokers (> 10 cigarettes, or equivalent, per day) or are unable or unwilling to refrain from nicotine during CRU admissions

Exclusion Criteria for EU Site only --

• Regular use of known drugs of abuse and/or positive findings on urinary drug screening
• Evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies
• Evidence of hepatitis C and/or positive hepatitis C antibodies

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; as capsules, administered orally once daily for two weeks
Experimental: 20 mg LY2393910	Drug: LY2393910; as capsules, administered orally once daily for two weeks
Experimental: 60 mg LY2393910	Drug: LY2393910; as capsules, administered orally once daily for two weeks
Experimental: 150 mg LY2393910	Drug: LY2393910; as capsules, administered orally once daily for two weeks
Experimental: 450 mg LY2393910	Drug: LY2393910; as capsules, administered orally once daily for two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Clinically Significant Effects	Over four weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of LY2393910, Area Under the Curve (AUC)	From predose Day 1 up until Day 19
Change from baseline to day 28 in glucagon	Baseline, day 28
Pharmacokinetics of LY2393910, maximum concentration (Cmax)	From predose Day 1 up until Day 19
Change from baseline to day 28 in glucose-like peptide 1 (GLP-1)	Baseline, day 28
Change from baseline to day 14 in insulin	baseline, day 14
Change from baseline to day 14 in proinsulin	baseline, day 14
Change from baseline to day 28 in glucose	baseline, day 28
Change from baseline to day 14 in C-peptide	baseline, day 14

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 3, 2010

Study Record Updates

• Last Update Posted (Estimate): June 10, 2011
• Last Update Submitted That Met QC Criteria: June 9, 2011
• Last Verified: June 1, 2011

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: 13183; I4B-FW-GPCB (Other Identifier: Eli Lilly and Company)