Clinical trial NCT01968070: A Study of LY3127760 in Healthy Participants
Official title: A Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of LY3127760 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-10-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline to Study Completion (Up To Day 42)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time Curve From Zero to Infinity (AUC 0-∞) of Single Dose LY3127760
timeFrame: Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
measure: PK: Maximum Observed Concentration (Cmax) of Single Dose LY3127760
timeFrame: Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
measure: PK: Time of Maximum Observed Concentration (Tmax) of Single Dose LY3127760
timeFrame: Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
measure: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC-tau (τ)] of Multiple Doses LY3127760
timeFrame: Day 28: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 Hours
measure: PK: Cmax of Multiple Doses LY3127760
timeFrame: Post last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours
measure: PK: Tmax of Multiple Doses LY3127760
timeFrame: Post-last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours
Other outcomes:
Locations:
city: Evansville
country: United States
facility: 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.
state: Indiana
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: 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.