A Study of LY2944876 in Healthy Japanese and Non-Japanese Participants

A Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of the Oxyntomodulin Analog, LY2944876, in Healthy Japanese Subjects and Healthy Non-Japanese Subjects

LY2944876 is an investigative drug for the treatment of Type 2 Diabetes Mellitus. Part A of the study will assess the safety and tolerability of single doses of LY2944876 in Japanese participants. Participation is expected to last up to about 7 weeks, not including screening.

Part B of the study will investigate the safety and tolerability of multiple doses of LY2944876 in non Japanese participants. Participation is expected to last up to about 8 weeks, not including screening.

All doses will be administered as injections into the fatty layer just beneath the skin.

Screening is required within 28 days prior to the start of the study. All participants will attend a post study safety assessment approximately 6 weeks after their final dose.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: LY2944876

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, 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: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males or female participants
• Are first generation Japanese participants (Part A) or non-Japanese participants (Part B)
• Have a body mass index (BMI) of 18.5 to 30 kilogram per meter square (kg/m^2), inclusive, for Part A and a BMI of 25 to 40 kg/m^2, inclusive, for Part B at screening
• Have normal blood pressure and heart rate (after approximately 5 minutes supine and approximately 2 minutes standing) as determined by the investigator at screening

Exclusion Criteria:

• Have known allergies to LY2944876, related compounds or any components of the formulation, or history of significant atopy
• Have an abnormality in the 12-lead electrocardiogram (ECG) at screening and/or baseline that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
• Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase greater than 2 times the upper limit of normal (ULN) at screening and/or baseline
• Have known or ongoing psychiatric disorders considered clinically significant in the opinion of the investigator
• Have undergone any form of bariatric surgery
• Have fasting blood glucose levels greater than or equal to (≥) 7 millimoles per liter (mmol/L) [≥126 milligrams per deciliter (mg/dL)] at screening
• Have fasting triglycerides levels ≥300 mg/dL (3.4 mmol/L) at screening
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or an alanine transaminase (ALT) or aspartate aminotransferase (AST) levels greater than (>) 2.5 times the ULN at screening and/or baseline
• Have used or intend to use medications that promote weight loss, within 3 months prior to screening, for the duration of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Single Dose, Cohorts 1-3); Single dose of placebo matching LY2944876 administered subcutaneous (SC) on Day 1	Drug: Placebo; Administered SC
Experimental: LY2944876 (Single Dose, Cohorts 1-3); Single dose of 10 milligrams (mg) of LY2944876 administered SC on Day 1	Drug: LY2944876; Administered SC
Placebo Comparator: Placebo (Multiple Dose, Cohort 4); Placebo matching LY2944876 administered once daily SC on Days 1-7	Drug: Placebo; Administered SC
Experimental: LY2944876 (Multiple Dose, Cohort 4); 40 mg LY2944876 administered once daily SC on Days 1-7	Drug: LY2944876; Administered SC
Placebo Comparator: Placebo (Multiple, Cohort 5); Placebo matching LY2944876 administered once daily SC on Days 1, 4, 6, 8, 10 and 12	Drug: Placebo; Administered SC
Experimental: LY2944876 (Multiple Dose, Cohort 5, Titrated); LY2944876 in titrated doses of 15 mg on Day 1, 30 mg on Day 4, up to 60 mg on Day 6, and up to 80 mg on Days 8, 10 and 12 administered once daily SC	Drug: LY2944876; Administered SC

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	An SAE is any adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.	Pre-dose (PRD) through Study Completion (Up to Day 40)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876	Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53
Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876	Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 10, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Actual): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 15247; I7I-EW-XNAB (Other Identifier: Eli Lilly and Company)