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

NCT06256510 | Completed Phase 1

• 2 other identifiers: C48910392023-508518-40-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (4)

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

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

• Cmax of Midazolam following multiple doses of Vepdegestrant

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

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

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

• AUCinf of Midazolam following multiple doses of Vepdegestrant

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

Secondary Outcomes (19)

• Cmax of Midazolam following a single dose of Vepdegestrant

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

• AUCinf of Midazolam following a single dose of Vepdegestrant

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

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

  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.

• Number of Participants With Clinical Laboratory Abnormalities

  Baseline up to Period 2 Day 20

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

  Baseline up to Period 2 Day 20

Study Arms (1)

Midazolam with and without Vepdegestrant

EXPERIMENTAL

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

Midazolam DRUG

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

Midazolam with and without Vepdegestrant

Vepdegestrant DRUG

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

Also known as: ARV-471, PF-07850327

Midazolam with and without Vepdegestrant

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Body mass index (BMI) of 16-32 kg/m2; and a total body weight \>45 kg (99 lb).
• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• 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.
• 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.
• 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.
• Current use of any prohibited concomitant medication(s). Refer to Section 6.9 Prior and Concomitant Therapy.
• 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).
• A positive urine drug test or alcohol breath test at discretion of investigator. A single repeat for positive drug screen may be allowed.
• 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.
• 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.
• 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)
• 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.

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (1)

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: February 8, 2024
• Primary Completion: April 16, 2024
• Study Completion: May 13, 2024
• Last Updated: January 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)