A Study of the Effect of Abemaciclib on Metformin and Iohexol in Healthy Participants

Study Overview
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Brief Summary
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This study will look at how a single dose of abemaciclib will impact the body's ability to get rid of two other drugs, metformin and iohexol. In addition, this study will evaluate the effect of a single dose of abemaciclib on kidney function by measuring blood and urine markers. Side effects will also be documented. Each participant will complete four study periods. During each study period, participants will stay in the clinical research unit for nine days and eight nights. The study will last approximately 10 weeks, not including screening. Screening is required within 28 days prior to the start of the study. This study is for research purposes only and is not intended to treat any medical condition.

Official Title
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Effect of Abemaciclib on Metformin Pharmacokinetics and Iohexol Clearance

Conditions
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Healthy

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Metformin
* Drug: Iohexol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy surgically sterile or postmenopausal females and sterile males Have a body mass index (BMI) between 18 and 32 kilograms per meter squared (kg/m²), inclusive at screening Exclusion Criteria: Have known allergies to abemaciclib, metformin, iodine, iohexol, related compounds, or any components of the formulation Regularly use known drugs of abuse and/or show positive findings on urinary drug screening Show evidence and/or positive antibodies of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Metformin<br>Single dose of placebo administered orally followed by a single dose of metformin administered orally in one of four study periods. | Drug: Metformin<br>* Administered orally<br>Drug: Placebo<br>* Administered orally<br>|
| Experimental: Abemaciclib + Metformin<br>Single dose of abemaciclib administered orally followed by a single dose of metformin administered orally in one of four study periods. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Metformin<br>* Administered orally<br>|
| Placebo Comparator: Placebo + Iohexol<br>Single dose of placebo administered orally followed by a single dose of iohexol administered intravenously (IV) in one of four study periods. | Drug: Iohexol<br>* Administered intravenously (IV)<br>Drug: Placebo<br>* Administered orally<br>|
| Experimental: Abemaciclib + Iohexol<br>Single dose of abemaciclib administered orally followed by a single dose of iohexol administered intravenously (IV) in one of four study periods. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Iohexol<br>* Administered intravenously (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-∞]) of Metformin was evaluated. | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated. | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | 
| Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin | Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated. | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol | Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated. | Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusion |