Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype
Phase 4
Withdrawn
- Conditions
- CYP3A4*22
- Interventions
- Registration Number
- NCT05691400
- Lead Sponsor
- University of Michigan Rogel Cancer Center
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CYP3A4*1/*1 Abemaciclib 150 MG Oral Tablet 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. CYP3A4*1/*22 Palbociclib 125Mg Tab 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. CYP3A4*1/*22 Abemaciclib 150 MG Oral Tablet 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. CYP3A4*22/*22 Abemaciclib 150 MG Oral Tablet 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. CYP3A4*1/*22 Ribociclib 200Mg Oral Tablet 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. CYP3A4*1/*1 Palbociclib 125Mg Tab 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. CYP3A4*22/*22 Palbociclib 125Mg Tab 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. CYP3A4*22/*22 Ribociclib 200Mg Oral Tablet 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. CYP3A4*1/*1 Ribociclib 200Mg Oral Tablet 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.
- Primary Outcome Measures
Name Time Method Effect of CYP3A4*22 on the Clearance of Palbociclib 2 days after initiation of Palbocicblib treatment To determine the effect of CYP3A4\*22 on the Clearance of Palbociclib when administered as a single dose to healthy volunteers.
Effect of CYP3A4*22 on the Clearance of Ribociclib up to 32 days after initiation of Study drug To determine the effect of CYP3A4\*22 on the Clearance of Ribociclib when administered as a single dose to healthy volunteers.
Effect of CYP3A4*22 on the CL of Abemaciclib up to 62 days after initiation of Study drug To determine the effect of CYP3A4\*22 on the Clearance of Abemaciclib when administered as a single dose to healthy volunteers.
- Secondary Outcome Measures
Name Time Method