A Study of LY3325656 in Healthy Participants and Participants With Type 2 Diabetes

A Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY3325656 After Single Dose in Healthy Subjects and Patients With Type 2 Diabetes

The aim of this trial is to evaluate the safety of single doses of a study drug known as LY3325656 that is given orally to healthy participants and participants with type 2 diabetes. Information about any side effects that may occur will be collected.

It will also investigate how much of the study drug gets into the blood stream, and how long it takes the body to get rid of it.

The study consists of two parts. Part A will study healthy participants over approximately 12 weeks and Part B will study participants with type 2 diabetes over approximately 5 weeks, excluding screening. Screening is required within 28 days of the start of the study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Sitagliptin; Drug: LY3325656; Drug: Liraglutide

• Study Type: Interventional
• Enrollment (Actual): 80
• 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, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
  • Singapore, Singapore, 117597
    • For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time 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: Yes
• Genders Eligible for Study: All

Description

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 18.5 kilograms per square meter (kg/m²)
• Have blood pressure, pulse rate, blood and urine laboratory test results acceptable for the study

For participants with Type 2 Diabetes Mellitus:

• Have diabetes controlled on diet and exercise with or without metformin for at least 30 days prior to screening, or on sulfonylureas with or without metformin
• Have a glycated hemoglobin (HbA1c) value of greater than or equal to 7% and less than or equal to 11% at screening (exercise with or without metformin)
• Have a HbA1c value of greater than or equal to 7% and less than or equal to 8.5% at screening (sulfonylureas with or without metformin)

Exclusion Criteria:

For all participants:

• Are currently participating in another clinical study or completed one in the last 30 days
• Are allergic to LY3325656 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
• Are infected with hepatitis B
• Are infected with human immunodeficiency virus (HIV)
• Have donated more than 450 mL of blood in the last 3 months or if 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 Type 2 Diabetes Mellitus:

• 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 6 months
• Show symptoms of high blood sugar e.g. frequent urination, always feeling thirsty, or unexpected weight loss

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Part A); Single oral dose of placebo (sugar pill) administered to healthy participants in up to 1 study period in Part A	Drug: Placebo; Administered orally
Experimental: LY3325656 (Part A); Single ascending dose of LY3325656 administered orally to healthy participants in up to 3 study periods in Part A	Drug: LY3325656; Administered orally
Placebo Comparator: Placebo (Part B); Single oral dose of placebo (sugar pill) administered to participants with T2DM in 1 study period in Part B	Drug: Placebo; Administered orally
Experimental: LY3325656 (Part B); Single oral dose of LY3325656 administered to participants with T2DM in 1 study period in Part B	Drug: LY3325656; Administered orally
Active Comparator: Liraglutide (Part B); Single subcutaneous dose of liraglutide administered to participants with T2DM in 1 study period in Part B	Drug: Liraglutide; Administered subcutaneously
Experimental: LY3325656 + Sitagliptin (Part B); Single oral dose of LY3325656 and sitagliptin administered to participants with T2DM in 1 study period in Part B	Drug: Sitagliptin; Administered orally; Drug: LY3325656; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module	Baseline through approximately 12 weeks and 5 weeks after first administration of study drug in Parts A and B, respectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3325656	Pharmacokinetics: Area Under the Concentration Curve of LY3325656 From Time Zero to 24 Hours [AUC(0-24)]	Baseline up to 72 hours after each dose of study drug
Pharmacokinetics: Maximum Concentration (Cmax) of LY3325656	Pharmacokinetics: Maximum Concentration (Cmax) of LY3325656	Baseline up to 72 hours after each dose of study drug

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2017
• Primary Completion (Actual): April 5, 2018
• Study Completion (Actual): April 5, 2018

Study Registration Dates

• First Submitted: April 11, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Liraglutide; Sitagliptin Phosphate
• Other Study ID Numbers: 16433; I8U-MC-DMBA (Other Identifier: Eli Lilly and Company)

Drug and device information, study documents

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