AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD STUDY TO ESTIMATE THE EFFECT OF SINGLE AND MULTIPLE DOSES OF VEPDEGESTRANT (ARV-471, PF-07850327) ON THE PHARMACOKINETICS OF SINGLE DOSE MIDAZOLAM IN HEALTHY ADULT FEMALES OF NON-CHILDBEARING POTENTIAL.
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam when administered alone
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Midazolam (Drug)
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.
Intervention: Vepdegestrant (Drug)
Outcomes
Primary Outcomes
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
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
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
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
- Number of Participants With Clinical Laboratory Abnormalities(Baseline up to Period 2 Day 20)
- Number of Participants With Abnormalities in Physical Examinations(Baseline up to Period 2 Day 20)
- AUClast of Midazolam following a slinge dose of Vepdegestrant(Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose)
- 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)
- Tmax of Midazolam following a slinge 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.)
- Tmax 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)
- Vz/F 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)
- Vz/F of Midazolam following a slinge 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 Clinically Significant Change From Baseline in Vital Signs(Baseline up to Period 2 Day 20)
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline up to Period 2 Day 20)
- Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (AUClast) 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)
- AUClast 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)
- Time for Cmax (Tmax) 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)
- Apparent clearance (CL/F) 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)
- CL/F 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)
- CL/F of Midazolam following a slinge dose of Vepdegestrant(Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hour post-dose)
- Apparent volume of distribution (Vz/F) 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)