CClinicalTrials.gg
CompletedNCT06256510Updated Jan 21, 2025

A Study to Learn If the Study Medicine Called Vepdegestrant Changes How the Body Processes the Other Study Medicine Called Midazolam

A Phase 1 interventional study of Midazolam and Vepdegestrant in Healthy Participants, sponsored by Pfizer. Completed at 1 site in Belgium. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-21.

Sponsored by Pfizer · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study summary

The purpose of this study is to learn if the study medicine called Vepdegestrant changes how the body processes the other study medicine called Midazolam.

This study is seeking participants who:

  • female who cannot have children.
  • are 18 years or older.
  • are overtly healthy as decided by medical tests.
  • have a body mass index (BMI) of 16 to 32 kilogram per meter squared.
  • have a total body weight of more than 45 kilograms (99 pounds).

All participants in this study will receive one dose of midazolam alone by mouth in Period 1. In Period 2, all participants will receive vepdegestrant by mouth once a day for 15 days. Participants will also receive one dose of midazolam by mouth on day 1 and day 15.

The levels of midazolam in Period 1 will be compared to the levels of midazolam in Period 2 Day 1 and Day 15 to decide if vepdegestrant affects how midazolam is processed differently in healthy adults.

The study duration is 22 days and includes two periods. Participants will stay in the clinical research unit through the end of period 2. A follow-up visit for each participant takes place at 28 to 35 days after taking the study medicine for the last time.

02

Conditions studied

  • Healthy Participants
03

In context

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Female participants of non-childbearing potential aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  2. Body mass index (BMI) of 16-32 kg/m2; and a total body weight >45 kg (99 lb).
  3. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  4. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion criteria

Exclusion Criteria:

  1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

    • Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy)
    • History of HIV infection, hepatitis B, or hepatitis C; positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination with an isolated positive hepatitis B surface antibody (HBsAb) result is allowed.
  2. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  3. Use of prescription or nonprescription drugs and dietary and herbal supplements, grapefruit/grapefruit containing products, and Seville orange/Seville orange containing products within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention. Refer to Section 6.9 Prior and Concomitant Therapy for additional details.

    • Moderate or strong CYP3A/P-gp inducers which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
    • Moderate or strong CYP3A/P-gp inhibitors which are prohibited within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
  4. Current use of any prohibited concomitant medication(s). Refer to Section 6.9 Prior and Concomitant Therapy.
  5. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
  6. A positive urine drug test or alcohol breath test at discretion of investigator. A single repeat for positive drug screen may be allowed.
  7. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants \<60 years; and ≥150/90 mm Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
  8. Standard 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete left bundle branch block (LBBB), signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
  9. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or Total Bilirubin Level ≥1.25 × upper limit of normal (ULN)
  10. Renal impairment as defined by an estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73 m2. Based upon participant age at screening, eGFR is calculated using the recommended chronic kidney disease epidemiology (CKD-EPI) equations in Section 10.6.2 to determine eligibility and to provide a baseline to quantify any subsequent kidney safety events.
  11. History of alcohol abuse or repeated binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 4 or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
  12. History of use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day.
  13. History of hypersensitivity reactions to midazolam and vepdegestrant, or any of the formulation components of midazolam and vepdegestrant.
  14. Unwilling or unable to comply with the criteria in the Section 5.3 of this protocol.
  15. Investigator site staff directly involved in the conduct of the study and Investigator site staff's family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and site staff's, sponsor's and sponsor delegate's family members.
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    Midazolam with and without Vepdegestrant

    Midazolam administered as a single dose in Period 1 Day 1, and Period 2 Day 1 and Day 15. Vepdegestrant administered once a day for 15 days in Period 2.

    Drug: Midazolam · Drug: Vepdegestrant

Interventions

  • DrugMidazolam

    Participants will receive a single dose of Midazolam by mouth in Period 1 Day 1, and Period 2 Day 1 and Day 15

  • DrugVepdegestrant

    Participants will receive Vepdegestrant by mouth once a day for 15 days in Period 2.

    Also known as: ARV-471, PF-07850327

06

What researchers measure

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  2. Cmax of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

  3. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  4. AUCinf of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

Secondary outcomes

  1. Cmax of Midazolam following a single dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  2. AUCinf of Midazolam following a single dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  3. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Time the participant provides informed consent through and including follow-up contact occurring 28 to 35 calendar days after the last administration of the study intervention.

  4. Number of Participants With Clinical Laboratory Abnormalities

    Time frame: Baseline up to Period 2 Day 20

  5. Number of Participants With Clinically Significant Change From Baseline in Vital Signs

    Time frame: Baseline up to Period 2 Day 20

  6. Number of Participants With Electrocardiogram (ECG) Abnormalities

    Time frame: Baseline up to Period 2 Day 20

  7. Number of Participants With Abnormalities in Physical Examinations

    Time frame: Baseline up to Period 2 Day 20

  8. Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (AUClast) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  9. AUClast of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

  10. AUClast of Midazolam following a slinge dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  11. Time for Cmax (Tmax) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  12. Tmax of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

  13. Tmax of Midazolam following a slinge dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  14. Apparent clearance (CL/F) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  15. CL/F of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

  16. CL/F of Midazolam following a slinge dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  17. Apparent volume of distribution (Vz/F) of Midazolam when administered alone

    Time frame: Period 1 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

  18. Vz/F of Midazolam following multiple doses of Vepdegestrant

    Time frame: Period 2 - Day 15 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hour post-dose

  19. Vz/F of Midazolam following a slinge dose of Vepdegestrant

    Time frame: Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose

07

Study locations

1 site
  • Pfizer Clinical Research Unit - Brussels
    Brussels, Bruxelles-capitale, Région DE B-1070, Belgium
08

References and documents

Individual participant data

Plan to share: No — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 21, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06256510
Lead sponsor
Pfizer
Collaborators
Arvinas Estrogen Receptor, Inc.
Responsible party
Sponsor
First posted
Feb 13, 2024
Start date
Feb 8, 2024
Primary completion
Apr 16, 2024
Completion
May 13, 2024
Last update
Jan 21, 2025

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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