A Study of LY2623091 in Healthy Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LY2623091
* Drug: Itraconazole
* Drug: Simvastatin
* Drug: Tadalafil
* Drug: Diltiazem


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2623091 (Group 1)<br>LY2623091 administered orally once on Day 1 of Period 1. | Drug: LY2623091<br>* Administered orally<br>|
| Experimental: Itraconazole + LY2623091 (Group 1)<br>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: LY2623091<br>* Administered orally<br>Drug: Itraconazole<br>* Administered orally<br>|
| Experimental: Simvastatin (Group 2)<br>20 mg simvastatin administered orally once daily on Day 1. | Drug: Simvastatin<br>* Administered orally<br>|
| Experimental: LY2623091 + Simvastatin (Group 2)<br>LY2623091 administered orally once daily on Days 3 - 13. Single oral dose of 20 mg simvastatin coadministered on Day 12. | Drug: LY2623091<br>* Administered orally<br>Drug: Simvastatin<br>* Administered orally<br>|
| Experimental: Tadalafil (Group 3)<br>5 mg tadalafil administered on Day 1 of Period 1. Arm is contingent on interim results from Groups 1 and 2. | Drug: Tadalafil<br>* Administered orally<br>|
| Experimental: Tadalafil + LY2623091 (Group 3)<br>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: LY2623091<br>* Administered orally<br>Drug: Tadalafil<br>* Administered orally<br>|
| Experimental: LY2623091 (Group 4)<br>LY2623091 administered orally once on Day 1 of Period 1. Arm is contingent on interim results from Groups 1 and 2. | Drug: LY2623091<br>* Administered orally<br>|
| Experimental: Diltiazem + LY2623091 (Group 4)<br>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<br>* Administered orally<br>Drug: Diltiazem<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |