Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype
Trial Snapshot
- Phase
- Phase 4
- Status
- Withdrawn
- Primary Endpoint
- Effect of CYP3A4*22 on the Clearance of Palbociclib
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
- •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*
- •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
Arms & Interventions
CYP3A4*1/*1
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.
Intervention: Palbociclib 125Mg Tab (Drug)
CYP3A4*1/*1
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.
Intervention: Ribociclib 200Mg Oral Tablet (Drug)
CYP3A4*1/*1
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.
Intervention: Abemaciclib 150 MG Oral Tablet (Drug)
CYP3A4*1/*22
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.
Intervention: Palbociclib 125Mg Tab (Drug)
CYP3A4*1/*22
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.
Intervention: Ribociclib 200Mg Oral Tablet (Drug)
CYP3A4*1/*22
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.
Intervention: Abemaciclib 150 MG Oral Tablet (Drug)
CYP3A4*22/*22
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.
Intervention: Palbociclib 125Mg Tab (Drug)
CYP3A4*22/*22
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.
Intervention: Ribociclib 200Mg Oral Tablet (Drug)
CYP3A4*22/*22
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.
Intervention: Abemaciclib 150 MG Oral Tablet (Drug)
Outcomes
Primary Outcomes
Effect of CYP3A4*22 on the Clearance of Palbociclib
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
No secondary outcomes reported