Trial Outcomes & Findings for A Study to Estimate the Effect of Multiple Dose Abrocitinib on Caffeine, Efavirenz, and Omeprazole in Healthy Participants (NCT NCT05067439)
NCT ID: NCT05067439
Last Updated: 2024-05-31
Results Overview
AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
COMPLETED
PHASE1
26 participants
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
2024-05-31
Participant Flow
A total of 26 participants were assigned and dosed in this study. In addition to the initial 13 participants planned, this study enrolled 13 replacement participants due to pharmacokinetic (PK) sample lost and remaining samples being not evaluable. Thus only 13 participants were included in the PK analysis.
Participant milestones
| Measure |
Periods 1 and 2
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1. They received abrocitinib 200 mg orally once daily (QD) on Days 1 - 10 Period 2, a single oral dose of omeprazole 10 mg on Day 2 Period 2, and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
|---|---|
|
Period 1
STARTED
|
26
|
|
Period 1
COMPLETED
|
26
|
|
Period 1
NOT COMPLETED
|
0
|
|
Period 2
STARTED
|
26
|
|
Period 2
COMPLETED
|
26
|
|
Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Estimate the Effect of Multiple Dose Abrocitinib on Caffeine, Efavirenz, and Omeprazole in Healthy Participants
Baseline characteristics by cohort
| Measure |
Periods 1 and 2
n=26 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1. They received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2, a single oral dose of omeprazole 10 mg on Day 2 Period 2, and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
|---|---|
|
Age, Customized
<18
|
0 Participants
n=5 Participants
|
|
Age, Customized
18-44
|
16 Participants
n=5 Participants
|
|
Age, Customized
45-64
|
10 Participants
n=5 Participants
|
|
Age, Customized
>=65
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
23 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=5 Participants
|
|
Body Mass Index
|
26.72 kg/m^2
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 2Population: This study enrolled 13 replacement participants as some of the pharmacokinetic (PK) samples from Day 8 Period 2 collected from the initial 13 participants were lost in transit and remaining samples were not evaluable. The PK data collected from the 13 replacement participants were included in the following descriptive and statistical summaries.
AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=13 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=13 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
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|---|---|---|---|
|
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Omeprazole
|
238.5 ng*hr/mL
Geometric Coefficient of Variation 101
|
688.8 ng*hr/mL
Geometric Coefficient of Variation 90
|
—
|
PRIMARY outcome
Timeframe: 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 2Population: This study enrolled 13 replacement participants as some of the PK samples from Day 8 Period 2 collected from the initial 13 participants were lost in transit and remaining samples were not evaluable. The PK data collected from the 13 replacement participants were included in the following descriptive and statistical summaries.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=12 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=11 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
|---|---|---|---|
|
AUCinf Corrected for Residual Concentrations (AUCinfCR) of Caffeine
|
19730 ng*hr/mL
Geometric Coefficient of Variation 46
|
26880 ng*hr/mL
Geometric Coefficient of Variation 28
|
—
|
PRIMARY outcome
Timeframe: 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 2Population: This study enrolled 13 replacement participants as some of the PK samples from Day 8 Period 2 collected from the initial 13 participants were lost in transit and remaining samples were not evaluable. The PK data collected from the 13 replacement participants were included in the following descriptive and statistical summaries.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=13 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=13 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on 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
|
5588 ng*hr/mL
Geometric Coefficient of Variation 20
|
6153 ng*hr/mL
Geometric Coefficient of Variation 24
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All 26 participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
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|---|---|---|---|
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Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
3 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.Population: All 26 participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
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|---|---|---|---|
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Number of Participants With Treatment-Related TEAEs and SAEs
TEAEs
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2 Participants
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0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Related TEAEs and SAEs
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At screening, on Day -1 Period 1 and Day 11 Period 2Population: All 26 participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
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|---|---|---|---|
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Number of Participants With Laboratory Abnormalities Regardless of Baseline
Urine hemoglobin >=1
|
0 Participants
|
0 Participants
|
7 Participants
|
|
Number of Participants With Laboratory Abnormalities Regardless of Baseline
Neutrophils >1.2x upper limit of normal (ULN)
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: At screening, on Day 1 Period 1 and Day 11 Period 2Population: All 26 participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 Participants
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
|
|---|---|---|---|
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Number of Participants With Clinically Significant Change in Vital Signs
|
0 Participants
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0 Participants
|
2 Participants
|
Adverse Events
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
Abrocitinib 200 mg QD + Omeprazole 10 mg
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 participants at risk
Healthy participants received single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together following an overnight fast on Day 1 Period 1.
|
Abrocitinib 200 mg QD + Omeprazole 10 mg
n=26 participants at risk
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2, and a single oral dose of omeprazole 10 mg within approximately 5 minutes after administration of abrocitinib on Day 2 Period 2.
|
Abrocitinib 200 mg QD + Caffeine 100 mg + Efavirenz 50 mg + Omeprazole 10 mg
n=26 participants at risk
Healthy participants received abrocitinib 200 mg orally QD on Days 1 - 10 Period 2 and single oral doses of caffeine 100 mg, efavirenz 50 mg, and omeprazole 10 mg together on Day 8 Period 2.
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|---|---|---|---|
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Investigations
Blood pressure increased
|
0.00%
0/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
7.7%
2/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Nervous system disorders
Tremor
|
7.7%
2/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
3.8%
1/26 • 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.
The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER