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

NCT05067439 | Completed Phase 1 Results FDA Drug

• 1 other identifier: B7451092
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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

Secondary Outcomes (4)

• Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

  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

  At screening, on Day -1 Period 1 and Day 11 Period 2

• Number of Participants With Clinically Significant Change in Vital Signs

  At screening, on Day 1 Period 1 and Day 11 Period 2

Study Arms (2)

Period 1

OTHER

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; Drug: Caffeine; Drug: Efavirenz

Period 2

OTHER

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; Drug: Omeprazole; Drug: Caffeine; Drug: Efavirenz

Interventions

Abrocitinib DRUG

200 mg once daily (QD)

Period 2

Omeprazole DRUG

single doses of 10 mg

Period 1; Period 2

Caffeine DRUG

single dose of 100 mg

Period 1; Period 2

Efavirenz DRUG

single doses of 50 mg

Period 1; Period 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be ≥18 years of age at the time of signing the Informed consent document (ICD).
• 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.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body mass index (BMI) of 17.5 to 32 kg/m2; and a total body weight \>50 kg (110 lb).
• 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.

You may not qualify if:

• 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
• Subjects with moderate to severe gastroesophageal reflux disease (GERD) symptoms, or any condition affecting drug absorption e.g. gastrectomy, cholecystectomy
• 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.
• 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.
• 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.
• 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).
• 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.
• History of hypersensitivity, intolerance, or allergic reaction associated with prior exposure to caffeine, omeprazole, efavirenz and abrocitinib or any of their excipients.
• Subjects who may be at increased risk if dosed with efavirenz, including severe hepatic impairment (Child Pugh Class C), or a history of seizures.
• 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.
• 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.
• 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).
• Smokers and/or subjects who used nicotine-based products within three months prior to the first dose of the investigational product.
• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Centers of America ( Hollywood )

Hollywood, Florida, 33024, United States

Location

Related Publications (1)

• Wang X, Dowty ME, Tripathy S, Le VH, Huh Y, Curto M, Winton JA, O'Gorman MT, Chan G, Malhotra BK. Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals. Eur J Drug Metab Pharmacokinet. 2024 May;49(3):367-381. doi: 10.1007/s13318-024-00893-5. Epub 2024 Mar 30.

  PMID: 38554232 DERIVED

Related Links

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

MeSH Terms

Interventions

abrocitinib; Omeprazole; Caffeine; efavirenz

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Xanthines; Alkaloids; Purinones; Purines

Limitations and Caveats

In addition to the initial 13 participants, 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. This replacement is consistent with the protocol.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 5, 2021
• Study Start: October 21, 2021
• Primary Completion: February 26, 2022
• Study Completion: February 26, 2022
• Last Updated: May 31, 2024
• Results First Posted: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)