Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype

Study Overview
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Brief Summary
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The objective of this study is to estimate the effect of CYP3A4*22 on the clearance and area under the plasma concentration-time curve of Palbociclib, Ribociclib, and Abemaciclib

Official Title
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Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype

Conditions
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CYP3A4*22

Intervention / Treatment
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* Drug: Palbociclib 125Mg Tab
* Drug: Ribociclib 200Mg Oral Tablet
* Drug: Abemaciclib 150 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MGI participant with genotype of interest (e.g., CYP3A4*1/*1, CYP3A4*1/*22, or CYP3A4*22/*22) and consented to recontact for future research Age≥18 Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Concurrent use of a moderate or strong inhibitor or inducer of CYP3A4, based on the current version of the Drug Interactions Flockhart Table™, available at this link or by google search: https://drug-interactions.medicine.iu.edu/MainTable.aspx Carriers another variant known to affect CYP3A4 activity, particularly CYP3A4*20. Active malignancy or other disease state that would affect the pharmacokinetics of CDK4/6 inhibitors or place the participant at particular risk of toxicity from a single dose of a CDK4/6 inhibitor, in the opinion of the study team History of allergic reaction to CDK4/6 inhibitor Pregnancy or nursing female

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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: arms are designated based off of genotype; however, treatment is the same for each arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYP3A4*1/*1<br>This arm will include subjects with CYP3A4*1/*1 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration. | Drug: Palbociclib 125Mg Tab<br>* 125 mg single dose<br>* Other names: ibrance;Drug: Ribociclib 200Mg Oral Tablet<br>* 200 mg single dose<br>* Other names: kisqali;Drug: Abemaciclib 150 MG Oral Tablet<br>* 150 mg single dose<br>* Other names: verzenio;|
| Experimental: CYP3A4*1/*22<br>This arm will include subjects with CYP3A4*1/*22 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration. | Drug: Palbociclib 125Mg Tab<br>* 125 mg single dose<br>* Other names: ibrance;Drug: Ribociclib 200Mg Oral Tablet<br>* 200 mg single dose<br>* Other names: kisqali;Drug: Abemaciclib 150 MG Oral Tablet<br>* 150 mg single dose<br>* Other names: verzenio;|
| Experimental: CYP3A4*22/*22<br>This arm will include subjects with CYP3A4*22/*22 genotype. They will receive a single oral dose of each CDK4/6 inhibitor on separate days, with at least 6 days and no more than 30 days between each medication. All participants will receive the medications in the same order: Palbociclib, Ribociclib, Abemaciclib Ribociclib- 200 mg tablet Abemaciclib- 150 mg tablet Palbociclib-125 mg tablet PK sampling will be done at the time of drug administration and at different time points until 48 hours post administration. | Drug: Palbociclib 125Mg Tab<br>* 125 mg single dose<br>* Other names: ibrance;Drug: Ribociclib 200Mg Oral Tablet<br>* 200 mg single dose<br>* Other names: kisqali;Drug: Abemaciclib 150 MG Oral Tablet<br>* 150 mg single dose<br>* Other names: verzenio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of CYP3A4*22 on the Clearance of Palbociclib | To determine the effect of CYP3A4*22 on the Clearance of Palbociclib when administered as a single dose to healthy volunteers. | 2 days after initiation of Palbocicblib treatment | 
| Effect of CYP3A4*22 on the Clearance of Ribociclib | To determine the effect of CYP3A4*22 on the Clearance of Ribociclib when administered as a single dose to healthy volunteers. | up to 32 days after initiation of Study drug | 
| Effect of CYP3A4*22 on the CL of Abemaciclib | To determine the effect of CYP3A4*22 on the Clearance of Abemaciclib when administered as a single dose to healthy volunteers. | up to 62 days after initiation of Study drug |