A Study of LY3127760 in Healthy Participants

A Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of LY3127760 in Healthy Subjects

The main purposes of this study are to evaluate the safety and how well the body handles single and multiple doses of increasing strength of study drug, LY3127760. This study includes three parts. Part 3 may be initiated at sponsor's discretion, based on data from Part 2. Participants will only enroll in 1 of the 3 study parts. This study will last approximately 7 to 13 weeks, depending on part. Screening must be completed within 28 days prior to enrollment.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Celecoxib; Drug: LY3127760

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States, 47710
      • 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:

• Overtly healthy males or females as determined by medical history and physical examination
• Male participants agree to use a reliable method of birth control during the study and 3 months following the last dose of the investigational product
• Female participants not of child-bearing potential
• Have a body mass index of 18.5 to 32 kilograms per square meter (kg/m^2) inclusive
• Are normotensive (defined as supine systolic blood pressure [BP] less than 140 millimeters of mercury [mm Hg] and diastolic BP less than 90 mm Hg) without use of any antihypertensives

Exclusion Criteria:

• Have known allergies to LY3127760, related compounds or any components of the formulation, celecoxib or sulfonamides, or history of significant atopy. Participants with known aspirin allergy or allergic reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded
• Have any current or prior history of a significant gastrointestinal illness such as peptic ulcer disease, gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease or chronic diarrhea
• Have evidence of other chronic liver disease, including but not limited to chronic alcoholic disease, nonalcoholic steatohepatitis, recent history (within 3 months of screening) of acute viral hepatitis or chronic autoimmune hepatitis
• Have used any NSAIDs, celecoxib, aspirin or acetaminophen (at doses greater than 1 gram per day), anticoagulants or antiplatelet agents within 14 days of admission

Part 2 and Part 3 only

• Have 1 plus pretrial pitting edema or 2 plus ankle or pedal edema

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LY3127760 (Single); Single oral dose of up to 900 milligram (mg) LY3127760 administered in up to 3 of 3 study periods.	Drug: Placebo; Administered orally; Drug: LY3127760; Administered orally
PLACEBO_COMPARATOR: Placebo (Single); Single oral dose of placebo administered in up to 2 of 3 study periods. Placebo matches LY3127760 in appearance.	Drug: Placebo; Administered orally; Drug: LY3127760; Administered orally
EXPERIMENTAL: LY3127760 (Multiple); Multiple ascending oral doses of up to 900 mg LY3127760 administered once or twice daily (QD or BID) for 28 days.	Drug: Placebo; Administered orally; Drug: LY3127760; Administered orally
PLACEBO_COMPARATOR: Placebo (Multiple); Multiple oral doses of placebo administered QD or BID for 28 days. Placebo matches LY3127760 in appearance.	Drug: Placebo; Administered orally; Drug: LY3127760; Administered orally
ACTIVE_COMPARATOR: Celecoxib (Multiple); Multiple oral doses of 400 mg celecoxib administered QD for 28 days.	Drug: Placebo; Administered orally; Drug: Celecoxib; Administered orally; Drug: LY3127760; 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	Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.	Baseline to Study Completion (Up To Day 42)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time Curve From Zero to Infinity (AUC 0-∞) of Single Dose LY3127760		Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Maximum Observed Concentration (Cmax) of Single Dose LY3127760		Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Time of Maximum Observed Concentration (Tmax) of Single Dose LY3127760		Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC-tau (τ)] of Multiple Doses LY3127760	AUC-tau (τ) where τ is 24-hours for the 20 mg, 60 mg, and 200 mg cohorts, and 12-hours for the 300 mg cohort.	Day 28: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 Hours
PK: Cmax of Multiple Doses LY3127760		Post last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours
PK: Tmax of Multiple Doses LY3127760		Post-last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Jin Y, Smith C, Hu L, Coutant DE, Whitehurst K, Phipps K, McNearney TA, Yang X, Ackermann B, Pottanat T, Landschulz W. LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles. Clin Transl Sci. 2018 Jan;11(1):46-53. doi: 10.1111/cts.12497. Epub 2017 Aug 30.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (ESTIMATE): October 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: 15181; I7A-MC-EACA (OTHER: Eli Lilly and Company)