This is a Phase 1, open-label, multiple dose, single fixed-sequence, 2-period study to evaluate the effect of abrocitinib on the pharmacokinetics (PK) of caffeine, efavirenz and omeprazole in healthy adult participants. A total of approximately 13 healthy male and/or female participants will be enrolled in the study to obtain at least 12 evaluable participants who complete the study. Participants who withdraw from the study or are considered non-evaluable may be replaced at the discretion of the sponsor. Participants will be screened within 28 days of the first dose of study intervention. Participants will have a phone contact 3 days prior to Day 1 dosing (Day -3) in Period 1 as a reminder to abstain from caffeine-containing products. Participants will be admitted to the clinical research unit (CRU) at least 24 hours prior to Day 1 dosing (Day 1) in Period 1. Participants will remain in the CRU for a total of 15 days and 14 nights. Participants will have a telephone contact between 28-35 calendar days after the last administration of the investigational product.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
26
200 mg once daily (QD)
single doses of 10 mg
single dose of 100 mg
single doses of 50 mg
Research Centers of America ( Hollywood )
Hollywood, Florida, United States
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Omeprazole
AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 hour post-dose on Day 1 Period 1 and Day 8 Period 2
AUCinf Corrected for Residual Concentrations (AUCinfCR) of Caffeine
AUCinfCR was defined as AUCinf corrected for residual concentrations. AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Two participants in Period 1 and 1 participant in Period 2 had pre-dose caffeine concentrations that were greater than 5% of the corresponding maximum plasma concentration (Cmax). Therefore, AUCinf was corrected for the residual concentrations for these participants.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 hour post-dose on Day 1 Period 1 and Day 8 Period 2
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration Corrected for Residual Concentrations (AUClastCR) of Efavirenz
AUClastCR was defined as AUClast corrected for residual concentrations. AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. Eight participants in Period 2 had pre-dose efavirenz concentrations that were greater than 5% of the corresponding Cmax. Therefore, AUClast was corrected for the residual concentrations for these participants.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 hour post-dose on Day 1 Period 1 and Day 8 Period 2
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or worsened relative to pretreatment state. An SAE was defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect.
Time frame: Up to 48 days after the first dose in period 1. This includes 3 days of period 1, 10 days of period 2 and 28-25 days of the follow-up period.
Number of Participants With Treatment-Related TEAEs and SAEs
Adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or worsened relative to pretreatment state. An SAE was defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. Causality of the TEAEs and SAEs was judged by the investigator.
Time frame: Up to 48 days after the first dose in period 1. This includes 3 days of period 1, 10 days of period 2 and 28-25 days of the follow-up period.
Number of Participants With Laboratory Abnormalities Regardless of Baseline
Hematology parameters included hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, cystatin C, glucose (fasting), calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Only those categories in which at least 1 participant had data were reported. Number of Participants With Laboratory Abnormalities Regardless of Baseline in data table indicates the number of participants who had the laboratory abnormality at least 1 of the timepoints when the laboratory tests were done.
Time frame: At screening, on Day -1 Period 1 and Day 11 Period 2
Number of Participants With Clinically Significant Change in Vital Signs
Vital sign measurements included supine blood pressure, pulse rate, respiratory rate, and temperature. Any safety assessments (vital sign measurements) including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the investigator were considered meeting the AE definition and are listed below. Only those categories in which at least 1 participant had data were reported.
Time frame: At screening, on Day 1 Period 1 and Day 11 Period 2
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