The purpose of the study is to investigate the effect of multiple doses of a proton-pump inhibitor (PPI) esomeprazole on the PK of vepdegestrant under fed conditions in healthy adult participants. All participants in this study will receive one dose of vepdegestrant alone by mouth in Period 1. In Period 2, everyone will receive esomeprazole by mouth once a day for multiple days. Participants will also receive one dose of vepdegestrant by mouth. The levels of vepdegestrant in Period 1 will be compared to the levels of vepdegestrant in Period 2 to determine if the PPI affects how vepdegestrant is processed differently in healthy adults.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
12
experimental
Experimental treatment to assess an endpoint
Pfizer Clinical Research Unit - New Haven
New Haven, Connecticut, United States
Maximum observed plasma concentration (Cmax) of vepdegestrant when vepdegestrant is administered alone
Time frame: Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
Maxium observed plasma concentration of vepdegestrant when vepdegestrant is administered with esomeprazole
Time frame: Period 2 - Day 5 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
Area under the curve from time zero to extrapolated infinite time (AUCinf) when vepdegestrant is administered alone
AUCinf=area under the plasama concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0-t) plus AUC (t-inf)
Time frame: Period 1 - Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
Area under the curve from time zero to extrapolated infinite time (AUCinf) when vepdegestrant is administered with esomeprazole
AUCinf=area under the plasama concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0-t) plus AUC (t-inf)
Time frame: Period 2 - Day 5 pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose
number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
An AE is any untoward medical occurence in a participant who received study drug without regard to possibility of causal relationship with the study treatmnet. SAE is defined as one of hte following: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitues a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset data occurring during the on-treatment period. AEs include all SAEs and non-SAEs.
Time frame: time the participant provides informed censent through and including follow-up contact occurring 28-35 calendar days after the last administration of the study intervention
Number of participants with clinical laboratory abnormalities
Following parameters were analyezed for laboratory examination: hematology (Hemoglobin, Hematocrit, RBC count, Platelet count, WBC count, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); liver function (AST, ALT, Total bilirubin, Alkaline phosphatase, Albumin, Total protein); renal function (blood Urea nitrogen, Creatinine, Cystatin Ca, uric acid); eletrolytes (Calcium, Sodium, Potassium Chloride, Total CO2 (bicarbonate)); clinical chemistry (glucose); urinalysis (dipstick \[decimal logarithm of reciprocal of hydrogen ion activity \[pH\] of urine, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, bilirubin\], microscopy If Hb/RBC abnormal: MCV, MCH, MCHC )
Time frame: baseline up to Period 2 Day 12
Number of participants with electrocardiogram (ECG) abnormalities
ECG abnormalities criteria include 2) a postdose QTcF is increased by \>60 ms from the baseline and is \>450 ms; or b) an absolute QTcF value is \>500 ms for any scheduled ECG.
Time frame: Baseline up to Period 2 Day 12
Number of participans with clinically significant change from baseline in vital signs
Blood pressure and pulse rate will be performed following at least a 5-minute rest in a supine position
Time frame: Baseline up to Period 2 Day 12
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