Clinical trial NCT04903093: A Study Evaluating Relative Bioavailability of an Oral Suspension of Abrocitinib and Effect of an Acid Reducing Agent on the Bioavailability of Abrocitinib and Assessing the Taste of Abrocitinib Oral Formulations.
Official title: A PHASE 1, RANDOMIZED, CROSSOVER STUDY TO EVALUATE RELATIVE BIOAVAILABILITY OF ABROCITINIB ORAL SUSPENSION AND EFFECT OF AN ACID-REDUCING AGENT ON THE BIOAVAILABILITY OF ABROCITINIB COMMERCIAL TABLET AND TO ASSESS THE TASTE OF ABROCITINIB ORAL FORMULATIONS IN HEALTHY ADULT PARTICIPANTS AGED 18 TO 55 YEARS OF AGE.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Abrocitinib
Atopic Dermatitis
Healthy Volunteers
Relative Bioavailability
Taste Assessment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study consists of 2 parts: Part A is to estimate the relative bioavailability of a single 200 mg dose of abrocitinib oral suspension (Test formulation) compared to the commercial abrocitinib tablet (200 mg) (Reference formulation). The effect of an acid-reducing agent on the pharmacokinetics of abrocitinib and its metabolites will also be evaluated by administering abrocitinib 200 mg commercial tablet with or without famotidine 40 mg, as an acid-reducing agent. Part B is to assess the taste and palatability of six different abrocitinib oral suspension formulations. Additionally, the safety and tolerability of abrocitinib tablet (in Part A) and abrocitinib oral suspension formulations (in Part B) will be assessed when given with or without famotidine 40 mg once daily.

Detailed description: This is a Phase 1 randomized study in healthy participants to estimate the relative bioavailability of abrocitinib oral suspension (Test formulation) compared to commercial abrocitinib tablet (Reference formulation) under fasted condition. The effect of an acid-reducing agent on the pharmacokinetics of the commercial tablet formulation will be evaluated by administering abrocitinib 200 mg commercial tablet with famotidine 40 mg, as an acid-reducing agent. Assessment of taste and palatability of six different abrocitinib suspension formulations will also be performed. This study consists of 2 parts, as listed below:

Part A

Part A of the study will be an open label, randomized, single dose, crossover, 3-treatment, 6 sequence, 3-period design in healthy male and/or female adult participants (18-55 years). Healthy participants will be screened within 28 days prior to the first administration of the study intervention to confirm that they meet the participant selection criteria for the study. Eligible participants will be admitted to the CRU on Day -1 and will be confined in the CRU until discharge, on Day 2 of Period 9 in Part B, after completing both Parts A and B of the study. In Part A, participants will be randomized to receive one of the following: a single 200 mg dose of abrocitinib commercial tablet (Treatment A), a single 200 mg dose of abrocitinib oral suspension formulation 1 (Treatment B), or famotidine (40 mg) administered 120 minutes before a single 200 mg dose of abrocitinib commercial tablet (Treatment C). All participants will be fasting for at least 10 hours before taking abrocitinib.

Part B

Part B will be a single-blind, randomized, 6-period, crossover study in healthy male and/or female adult participants (18-55 years). For any new healthy participants joining Part B only, screening will be performed within 28 days prior to the first administration of the study intervention to confirm that they meet the participant selection criteria for the study. New participants enrolled in Part B only will be admitted to the CRU on Day -1 and will be confined in the CRU until discharge, which is Day 2 of Period 9. On Day 1 of each treatment period under fasted conditions, participants will receive a famotidine tablet (40 mg with 240 mL of room temperature water) administered 120 minutes before a single 200 mg dose of abrocitinib oral suspensions (Formulations 1 to 6) or administered a single 200 mg dose of abrocitinib oral suspension alone (Formulations 1 to 6), after a fast of at least 10 hours before abrocitinib administration.

Eligibility criteria: Inclusion Criteria:

* Male and female participants who are overtly 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 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
* Capable of giving signed informed consent.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C virus antibody (HCVAb).
* Other acute or chronic medical or psychiatric condition including recent (within the past year).

Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) or visible rash present during physical examination.

* Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product.
* A positive urine drug test.
* Selected laboratory abnormalities.
* History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
* History of tuberculosis (TB) (active or latent).
* Any history of chronic infections, any history of recurrent infections, any history of latent infections, or any acute infection within 2 weeks of baseline.
* Pregnant female participants; breastfeeding female participants; female participants of childbearing potential who are unwilling or unable to use an acceptable method of contraception.
* History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.

Primary outcomes:
measure: AUCinf of Abrocitinib Following the Administration of Abrocitinib Commercial Tablet, Abrocitinib Oral Suspension Formulation 1 or Famotidine Plus Abrocitinib Commerical Tablet
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Cmax of Abrocitinib Following the Administration of Abrocitinib Commercial Tablet, Abrocitinib Oral Suspension Formulation 1 or Famotidine Plus Abrocitinib Commerical Tablet
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Assessment of Overall Liking After Administering Each Abrocitinib Oral Suspension Formulation (Formulation [F]1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Mouth Feel After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Bitterness After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Tongue/Mouth Burn After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Salty Taste After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Sour Taste After Administering Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
measure: Assessment of Sweet Taste After Administering Abrocitinib Oral Suspension Formulation (F1-F6) in Part B
timeFrame: 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period.
Secondary outcomes:
measure: AUCinf of Abrocitinib Metabolite (PF-06471658/M1) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: AUCinf of Abrocitinib Metabolite (PF-07055087/M2) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: AUCinf of Abrocitinib Metabolite (PF-07054874/M4) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Cmax of Abrocitinib Metabolite (PF-06471658/M1) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Cmax of Abrocitinib Metabolite (PF-07055087/M2) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Cmax of Abrocitinib Metabolite (PF-07054874/M4) Following the Administration of Abrocitinib 1×200 mg Tablet With or Without Famotidine 40 mg in Part A
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose on Day 1 of each period.
measure: Number of Participants With Treatment-Emergent Adverse Event
timeFrame: Baseline up to follow-up (Day 36)
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to follow-up (Day 36)
measure: Number of Participants With Clinically Significant Vital Sign Values
timeFrame: Baseline up to follow-up (Day 36)
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
timeFrame: Baseline up to follow-up (Day 36)
measure: Number of Participants With Nausea AEs
timeFrame: Baseline up to follow-up (Day 36)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: