A Study of LY2623091 in Healthy Participants

A Study to Determine the Effect of CYP3A Inhibition on the Pharmacokinetics of LY2623091 and the Effect of LY2623091 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects

The first purpose of this study is to evaluate the effect of itraconazole (and possibly diltiazem) on the amount of LY2623091 in the blood stream and how long the body takes to get rid of it.

The second purpose of the study is to evaluate the effect of LY2623091 on the amount of simvastatin (and possibly tadalafil) in the blood stream and how long the body takes to get rid of it.

The safety and tolerability of LY2623091 when given with itraconazole, simvastatin and diltiazem or tadalafil will be evaluated.

There will be three groups of participants in this study. Results from Groups 1 and 2 will be analyzed during the study to determine whether to enroll participants in Group 3 or 4. The study is expected to last up to 40 days from the first dose to follow-up (inclusive). Screening may occur up to 28 days prior to enrollment.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Itraconazole; Drug: Tadalafil; Drug: Simvastatin; Drug: LY2623091; Drug: Diltiazem

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Inc

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 participants as determined by medical history, physical examination, clinical laboratory tests, and electrocardiograms (ECGs).
• Have a body mass index (BMI) between 18 and 32.0 kilograms per square meter (kg/m^2) inclusive, at screening
• Female participants must be of non-childbearing potential

Exclusion Criteria:

• In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2623091 (Group 1); LY2623091 administered orally once on Day 1 of Period 1.	Drug: LY2623091; Administered orally
Experimental: Itraconazole + LY2623091 (Group 1); 200 mg itraconazole administered orally twice daily on Day 1 of Period 2 and once daily on Days 2 - 20 of Period 2. Single oral dose of LY2623091 coadministered on Day 6 of Period 2.	Drug: Itraconazole; Administered orally; Drug: LY2623091; Administered orally
Experimental: Simvastatin (Group 2); 20 mg simvastatin administered orally once daily on Day 1.	Drug: Simvastatin; Administered orally
Experimental: LY2623091 + Simvastatin (Group 2); LY2623091 administered orally once daily on Days 3 - 13. Single oral dose of 20 mg simvastatin coadministered on Day 12.	Drug: Simvastatin; Administered orally; Drug: LY2623091; Administered orally
Experimental: Tadalafil (Group 3); 5 mg tadalafil administered on Day 1 of Period 1. Arm is contingent on interim results from Groups 1 and 2.	Drug: Tadalafil; Administered orally
Experimental: Tadalafil + LY2623091 (Group 3); LY2623091 administered orally once daily on Day 1 up to Day 15 of Period 2. 5 mg tadalafil co-administered once daily on Day 10 of Period 2. Arm is contingent on interim results from Groups 1 and 2.	Drug: Tadalafil; Administered orally; Drug: LY2623091; Administered orally
Experimental: LY2623091 (Group 4); LY2623091 administered orally once on Day 1 of Period 1. Arm is contingent on interim results from Groups 1 and 2.	Drug: LY2623091; Administered orally
Experimental: Diltiazem + LY2623091 (Group 4); 240 mg diltiazem administered once daily on Days 1 to 13 of Period 2. Single oral dose of LY2623091 coadministered on Day 4 of Period 2. Arm is contingent on interim results from Groups 1 and 2.	Drug: LY2623091; Administered orally; Drug: Diltiazem; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Maximum Drug Concentration (Cmax) of LY2623091	Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of LY2623091	Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY2623091	Group 1 (Days 1 and 6) Group 4 (Days 1 and 4): Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours (hr) postdose; additionally for Group 1 (Day 6): 264, 288, 312, 336, 360 hr postdose
Pharmacokinetics: Maximum Drug Concentration (Cmax) of Simvastatin and Simvastatin Acid	Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Simvastatin and Simvastatin Acid	Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of Simvastatin and Simvastatin Acid	Days 1 and 12: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (Estimate): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Urological Agents; Enzyme Inhibitors; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Antifungal Agents; Steroid Synthesis Inhibitors; Calcium Channel Blockers; Phosphodiesterase Inhibitors; 14-alpha Demethylase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil; Itraconazole; Simvastatin; Diltiazem
• Other Study ID Numbers: 15523; I7T-MC-RMAG (Other Identifier: Eli Lilly and Company)