A Multiple-dose Study of LY3031207 in Healthy Participants

A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3031207 in Healthy Subjects

The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream, and how long it takes the body to get rid of it when given to healthy Japanese and non-Japanese participants as multiple doses. In addition, effects of 28-day oral dosing of LY3031207 on the amount of a cholesterol-lowering drug (simvastatin) that gets into the blood stream and how long the body takes to get rid of it will be determined. The effects of LY3031207 after single and 28-day dosing on blood pressure will also be studied. Information about any side effects that may occur will be collected.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Celecoxib; Drug: Placebo; Drug: LY3031207; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States
      • 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 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overtly healthy individuals based on the history and physical examinations as determined by the investigator, including first generation Japanese
• Body mass index between 17.0 and 32.0 kilograms per square meter (kg/m^2), inclusive

Exclusion Criteria:

• Have known allergies to LY3031207 or any components of the formulation, simvastatin or related compounds (other 3-Hydroxy-3-Methyl-Glutaryl-CoA [HMG CoA] reductase inhibitors), celecoxib, or sulfonamides. Participants with known aspirin allergy or allergic reaction to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Daily oral administration of placebo for 28 days. Dose will match corresponding LY3031207 dosage.	Drug: Placebo; Capsules administered orally
EXPERIMENTAL: LY3031207; Daily oral administration of 25 milligrams (mg) LY3031207 up to 450 mg LY3031207 for 28 days.	Drug: LY3031207; Administered orally
ACTIVE_COMPARATOR: Celecoxib; Daily oral administration of 400 mg celecoxib for 28 days. Positive control for LY3031207.	Drug: Celecoxib; Administered orally
OTHER: LY3031207 + Simvastatin; Daily oral administration of 75 mg LY3031207 or 225 mg LY3031207 for 28 days. Single, oral 10 mg simvastatin open-label dose administered before and after 28-day dosing of LY3031207.	Drug: Simvastatin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs	A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Baseline to study completion (treatment completion and follow-up, up to 35 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207	Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.	Predose up to 48 hours post last dose at Day 28
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207	Area under the concentration versus time curve in a dosing interval (AUC[0-tau]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.	Predose up to 48 hours post last dose at Day 28
Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207	Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.	Predose up to 48 hours post last dose at Day 28
Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin		Predose up to 48 hours post dose at Day -3 and Day 28
Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin	Area under the concentration versus time curve over the range of all measureable concentrations (AUC[0-tlast]) of simvastatin.	Predose up to 48 hours post dose at Day -3 and Day 28
Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin		Predose up to 48 hours post dose at Day -3 and Day 28
Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion		Baseline, Predose up to 12 hours prior to last dose at Day 28
Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion		Baseline, Predose up to time of last dose at Day 28
Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion		Baseline, Predose up to 12 hours prior to last dose at Day 28

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: June 25, 2012
• First Submitted That Met QC Criteria: July 2, 2012
• First Posted (ESTIMATE): July 3, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 27, 2019
• Last Update Submitted That Met QC Criteria: March 18, 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; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hormone Antagonists; Cyclooxygenase 2 Inhibitors; Prostaglandin Antagonists; Celecoxib; Simvastatin; LY3031207
• Other Study ID Numbers: 14284; I5W-EW-LBCB (OTHER: Eli Lilly and Company)