A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3031207 in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Eli Lilly and Company
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Placebo
Daily oral administration of placebo for 28 days. Dose will match corresponding LY3031207 dosage.
Intervention: Placebo (Drug)
LY3031207
Daily oral administration of 25 milligrams (mg) LY3031207 up to 450 mg LY3031207 for 28 days.
Intervention: LY3031207 (Drug)
Celecoxib
Daily oral administration of 400 mg celecoxib for 28 days. Positive control for LY3031207.
Intervention: Celecoxib (Drug)
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.
Intervention: Simvastatin (Drug)
Outcomes
Primary Outcomes
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
Time Frame: Baseline to study completion (treatment completion and follow-up, up to 35 weeks)
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.
Secondary Outcomes
- Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207(Predose up to 48 hours post last dose at Day 28)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin(Predose up to 48 hours post dose at Day -3 and 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)
- Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207(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: Time of Maximum Concentration (Tmax) of Simvastatin(Predose up to 48 hours post dose at Day -3 and Day 28)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207(Predose up to 48 hours post last dose at 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 Thromboxane A (TXA) Metabolite Excretion(Baseline, Predose up to 12 hours prior to last dose at Day 28)