A Study to Estimate the Effect of Multiple Dose Abrocitinib on Caffeine, Efavirenz, and Omeprazole in Healthy Participants

• ClinicalTrials.gov Identifier: NCT05067439
• Recruitment Status: Completed
• First Posted: October 5, 2021
• Last Update Posted: March 9, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Abrocitinib; Drug: Omeprazole; Drug: Caffeine; Drug: Efavirenz	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSE ABROCITINIB ON THE PHARMACOKINETICS OF SINGLE DOSES OF CAFFEINE, EFAVIRENZ, AND OMEPRAZOLE IN HEALTHY PARTICIPANTS
• Actual Study Start Date: October 21, 2021
• Actual Primary Completion Date: February 26, 2022
• Actual Study Completion Date: February 26, 2022

Arms and Interventions

Arm	Intervention/treatment
Period 1; In Period 1, all the participants will receive single doses of the probe drugs, including caffeine 100 mg, efavirenz 50 mg and omeprazole 10 mg, together on Day 1.	Drug: Omeprazole; single doses of 10 mg; Drug: Caffeine; single dose of 100 mg; Drug: Efavirenz; single doses of 50 mg
Period 2; In Period 2, participants will receive abrocitinib 200 mg once daily (QD) on Day 1-10, single dose of omeprazole on Day 2 and single dose of probe drugs together on Day 8.	Drug: Abrocitinib; 200 mg once daily (QD); Drug: Omeprazole; single doses of 10 mg; Drug: Caffeine; single dose of 100 mg; Drug: Efavirenz; single doses of 50 mg

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of omeprazole [ Time Frame: Period 1 Day 1, Period 2 Day 2, Period 2 Day 8 ]
2. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of omeprazole [ Time Frame: Period 1 Day 1, Period 2 Day 2, Period 2 Day 8 ]
3. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of caffeine [ Time Frame: Period 1 Day 1, Period 2 Day 8 ]
4. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of caffeine [ Time Frame: Period 1 Day 1, Period 2 Day 8 ]
5. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of efavirenz [ Time Frame: Period 1 Day 1, Period 2 Day 8 ]
6. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of efavirenz [ Time Frame: Period 1 Day 1, Period 2 Day 8 ]

Secondary Outcome Measures :

1. Number of subjects with adverse events (AEs) [ Time Frame: Screening up to 28-35 days after the last dose of investigational drug ]
2. Number of subjects with laboratory tests findings of potential clinical importance [ Time Frame: Screening up to Period 2 Day 11 ]
3. Number of subjects with clinically significant abnormal vital signs [ Time Frame: Screening up to Period 2 Day 11 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Participants must be ≥18 years of age at the time of signing the Informed consent document (ICD).
2. Male and female participants who are healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and cardiovascular tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Body mass index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lb).
5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, neurological diseases, or other systems diseases, allergic diseases including drug allergies but excluding untreated asymptomatic seasonal allergies at the time of dosing
2. Subjects with moderate to severe gastroesophageal reflux disease (GERD) symptoms, or any condition affecting drug absorption e.g. gastrectomy, cholecystectomy
3. History of human immunodeficiency virus (HIV) infection, positive test for HIV, hepatitis B, hepatitis C, positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb). Subjects previously vaccinated for hepatitis B may be allowed. However, subjects vaccinated with vaccines having live or attenuated components within 6 weeks of the first dose of study drug, or expecting to be vaccinated during the course of the trial are excluded.
4. Any psychiatric condition including recent or active suicidal ideation or behavior, other psychiatric conditions that may increase the risk of study participation, or, in the investigator's judgement, make the subject inappropriate for the study.
5. Evidence or history of clinically significant dermatological conditions, e.g. atopic dermatitis (AD) or psoriasis, or visible rash present during physical examination, history of disseminated herpes zoster or disseminated herpes simplex, or localized dermatomal herpes zoster.
6. History of chronic infections, recurrent infections or latent infections, e.g. tuberculosis (TB); Positive QuantiFERONE® TB GOLD test, any acute infection within 2-weeks of baseline (Day-1).
7. Malignancies or history of malignancies except for adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
8. History of hypersensitivity, intolerance, or allergic reaction associated with prior exposure to caffeine, omeprazole, efavirenz and abrocitinib or any of their excipients.
9. Subjects who may be at increased risk if dosed with efavirenz, including severe hepatic impairment (Child Pugh Class C), or a history of seizures.
10. Use of prescription or non-prescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug; herbal supplements and hormonal contraceptives and hormone replacement therapy (HRT) must be discontinued at least 28 days prior to the first dose of the investigational product; Depo-Provera® must be discontinued at least 6 months prior to dosing with investigational product.
11. Systemic therapy with any of the medicines that are moderate or strong cytochrome P450 (CYP)1A2, CYP2B6, or CYP2C19 inhibitors within 28 days or 5 half-lives (whichever is longer), or moderate or strong CYP1A2, CYP2B6 or CYP2C19 inducers within 28 days or 5-half-lives (whichever is longer) prior to the first dose.
12. Previous administration with any investigational drug within 30 days (or as determined by local requirements), or 5-half-lives preceding the first dose of study drug intervention used in this study (whichever is longer).
13. Smokers and/or subjects who used nicotine-based products within three months prior to the first dose of the investigational product.
14. Screening supine blood pressure (BP)≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at last 5 minutes of supine rest. If BP≥140 mmHg (systolic) or ≥90 mmHg (diastolic), the BP should be repeated 2 more times and the average of the 3BP values should be used to determine the subject's eligibility.
15. Abnormal baseline standard 12-lead electrocardiogram (ECG), QT interval >450 msec, QTcF>450 msec, . If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the subjects eligibility. Computer-interpreted ECGs should be 0ver-read by a physician experienced in reading ECGs before excluding a subject.
16. Subjects with abnormal blood chemistry; abnormal hematology including complete WBC count and differentials; estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2
17. History of alcohol abuse, binge drinking, or any illicit drug use or dependence within 6 months of screening. Positive urine drug test.
18. Pregnant females, breastfeeding females, female subjects of childbearing potential who are unwilling or unable to use one highly effective method of contraception as outlined in the protocol for the duration of the study and for at least, 28 days after the last dose of study intervention. Unwilling to comply with lifestyle considerations in the protocol.
19. Subjects who routinely consume more than five 8-ounce cups of coffee (or caffeine equivalent), or greater than 6 servings (1 serving is approximately equivalent to 125 mg of caffeine) of tea, cola or other caffeinated beverage per day.
20. Consumption of chocolate and chocolate-containing products (e.g. hot chocolate, ice cream, cookies, etc) within 48 hours prior to the first dose of study drug and during the study.
21. Consumption of charcoal-broiled beef within 7 days prior to the first dose of study drug as it is known to induce CYP1A2 enzyme.
22. Consumption of cruciferous vegetables (e.g. cauliflower, broccoli, Brussel sprouts and cabbage) within 7 days prior to the first dose of study drug as cruciferous vegetables are known to increase CYP1A2 activity
23. Blood donation (excluding plasma donation) of approximately 1 pint (500 ml) or more within 60 days prior to dosing.
24. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator and their respective family members.

Contacts and Locations

Locations

United States, Florida

Research Centers of America ( Hollywood )

Hollywood, Florida, United States, 33024

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05067439
• Other Study ID Numbers: B7451092
• First Posted: October 5, 2021
• Last Update Posted: March 9, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

abrocitinib; drug-drug interaction; omeprazole; caffeine; efavirenz

Additional relevant MeSH terms:

Efavirenz; Caffeine; Omeprazole; Abrocitinib; Central Nervous System Stimulants; Physiological Effects of Drugs; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Purinergic P1 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Protein Kinase Inhibitors