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

Sponsor
University of Michigan Rogel Cancer Center (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05691400
Collaborator
(none)
45
Enrollment
3
Arms
36
Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Palbociclib 125Mg Tab
  • Drug: Ribociclib 200Mg Oral Tablet
  • Drug: Abemaciclib 150 MG Oral Tablet
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Phase IV Multi-arm Study of CDK4/6 Pharmacokinetics in Healthy Volunteers With Known CYP3A4*22 Genotype
Anticipated Study Start Date :
Jan 1, 2023
Anticipated Primary Completion Date :
Jan 1, 2026
Anticipated Study Completion Date :
Jan 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Palbociclib 125Mg Tab
125 mg single dose
Other Names:
  • ibrance

    • Drug: Ribociclib 200Mg Oral Tablet
    200 mg single dose
    Other Names:
  • kisqali

    • Drug: Abemaciclib 150 MG Oral Tablet
    150 mg single dose
    Other Names:
  • verzenio

    		•
    Experimental: 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.

    Drug: Palbociclib 125Mg Tab
    125 mg single dose
    Other Names:
  • ibrance

    • Drug: Ribociclib 200Mg Oral Tablet
    200 mg single dose
    Other Names:
  • kisqali

    • Drug: Abemaciclib 150 MG Oral Tablet
    150 mg single dose
    Other Names:
  • verzenio

    		•
    Experimental: 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.

    Drug: Palbociclib 125Mg Tab
    125 mg single dose
    Other Names:
  • ibrance

    • Drug: Ribociclib 200Mg Oral Tablet
    200 mg single dose
    Other Names:
  • kisqali

    • Drug: Abemaciclib 150 MG Oral Tablet
    150 mg single dose
    Other Names:
  • verzenio

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Effect of CYP3A4*22 on the CL of Palbociclib [2 days after initiation of Palbocicblib treatment]

      To determine the effect of CYP3A4*22 on the CL of Palbociclib when administered as a single dose to healthy volunteers.

    2. Effect of CYP3A4*22 on the CL of Ribociclib [up to 32 days after initiation of Palbocicblib treatment]

      To determine the effect of CYP3A4*22 on the CL of Ribociclib when administered as a single dose to healthy volunteers.

    3. Effect of CYP3A4*22 on the CL of Abemaciclib [up to 62 days after initiation of Palbocicblib treatment]

      To determine the effect of CYP3A4*22 on the CL of Abemaciclib when administered as a single dose to healthy volunteers.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. MGI participant with genotype of interest (e.g., CYP3A4*1/1, CYP3A41/22, or CYP3A422/*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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • University of Michigan Rogel Cancer Center

    Investigators

    • Principal Investigator: Daniel L Hertz, University of Michigan Rogel Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Michigan Rogel Cancer Center
    ClinicalTrials.gov Identifier:
    NCT05691400
    Other Study ID Numbers:
    • UMCC 2022.106
    • HUM00220623
    First Posted:
    Jan 20, 2023
    Last Update Posted:
    Jan 20, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Palbociclib

    Study Results

    No Results Posted as of Jan 20, 2023