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

University of Michigan Rogel Cancer Center

Status and phase: Withdrawn; Phase 4

Conditions: CYP3A4*22

Treatments: Drug: Palbociclib 125Mg Tab; Drug: Abemaciclib 150 MG Oral Tablet; Drug: Ribociclib 200Mg Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT05691400

HUM00220623 (Other Identifier)

UMCC 2022.106

Details and patient eligibility

About

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

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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
2. Age≥18
3. Ability to understand and the willingness to sign a written informed consent.

Exclusion criteria

1. 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
2. Carriers another variant known to affect CYP3A4 activity, particularly CYP3A4*20.
3. 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
4. History of allergic reaction to CDK4/6 inhibitor
5. Pregnancy or nursing female

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

CYP3A4*1/*1

Experimental group

Description:

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.

Treatment:

Drug: Ribociclib 200Mg Oral Tablet

Drug: Abemaciclib 150 MG Oral Tablet

Drug: Palbociclib 125Mg Tab

CYP3A4*1/*22

Experimental group

Description:

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.

Treatment:

Drug: Ribociclib 200Mg Oral Tablet

Drug: Abemaciclib 150 MG Oral Tablet

Drug: Palbociclib 125Mg Tab

CYP3A4*22/*22

Experimental group

Description:

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.

Treatment:

Drug: Ribociclib 200Mg Oral Tablet

Drug: Abemaciclib 150 MG Oral Tablet

Drug: Palbociclib 125Mg Tab