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.

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Abrocitinib tablet
* Drug: Abrocitinib Suspension F1
* Drug: Abrocitinib Suspension F2
* Drug: Abrocitinib Suspension F3
* Drug: Abrocitinib Suspension F4
* Drug: Abrocitinib Suspension F5
* Drug: Abrocitinib Suspension F6
* Drug: Famotidine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Abrocitinib Tablet<br> | Drug: Abrocitinib tablet<br>* Single dose of abrocitinib 200 mg tablet will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part A: Abrocitinib Suspension F1<br> | Drug: Abrocitinib Suspension F1<br>* Single dose of abrocitinib 200 mg oral suspension formulation 1 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part A: Abrocitinib Tablet + Famotidine<br> | Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F1<br> | Drug: Abrocitinib Suspension F1<br>* Single dose of abrocitinib 200 mg oral suspension formulation 1 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F2<br> | Drug: Abrocitinib Suspension F2<br>* Single dose of abrocitinib 200 mg oral suspension formulation 2 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F3<br> | Drug: Abrocitinib Suspension F3<br>* Single dose of abrocitinib 200 mg oral suspension formulation 3 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F4<br> | Drug: Abrocitinib Suspension F4<br>* Single dose of abrocitinib 200 mg oral suspension formulation 4 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F5<br> | Drug: Abrocitinib Suspension F5<br>* Single dose of abrocitinib 200 mg oral suspension formulation 5 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F6<br> | Drug: Abrocitinib Suspension F6<br>* Single dose of abrocitinib 200 mg oral suspension formulation 6 will be administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Part B: Abrocitinib Suspension F1 + Famotidine<br> | Drug: Abrocitinib Suspension F1<br>* Single dose of abrocitinib 200 mg oral suspension formulation 1 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F2 + Famotidine<br> | Drug: Abrocitinib Suspension F2<br>* Single dose of abrocitinib 200 mg oral suspension formulation 2 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F3 + Famotidine<br> | Drug: Abrocitinib Suspension F3<br>* Single dose of abrocitinib 200 mg oral suspension formulation 3 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F4 + Famotidine<br> | Drug: Abrocitinib Suspension F4<br>* Single dose of abrocitinib 200 mg oral suspension formulation 4 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F5 + Famotidine<br> | Drug: Abrocitinib Suspension F5<br>* Single dose of abrocitinib 200 mg oral suspension formulation 5 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|
| Experimental: Part B: Abrocitinib Suspension F6 + Famotidine<br> | Drug: Abrocitinib Suspension F6<br>* Single dose of abrocitinib 200 mg oral suspension formulation 6 will be administered after an overnight fast of at least 10 hours.<br>Drug: Famotidine<br>* Single dose of famotidine 40 mg tablet administered 2 hours prior to abrocitinib formulations under fasted conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of Abrocitinib following the administration of 1x200 mg of abrocitinib tablet (AUCinf) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of Abrocitinib following the administration of 1x200 mg of abrocitinib tablet (Cmax) | Maximum observed plasma concentration. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of Abrocitinib following the administration of 1×200 mg of abrocitinib tablet with famotidine 40 mg in Part A (AUCinf) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of Abrocitinib following the administration of 1×200 mg of abrocitinib tablet with famotidine 40 mg in Part A (Cmax) | Maximum observed plasma concentration. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of Abrocitinib following the administration of 200 mg of abrocitinib oral suspension F1 (AUCinf) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of Abrocitinib following the administration of 200 mg of abrocitinib oral suspension F1 (Cmax) | Maximum observed plasma concentration. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| Number of subjects reporting overall liking after administering each abrocitinib oral suspension formulation (F1-F6) in Part B | Overall liking assesses the degree that a participant likes a drug formulation based on sensory attributes experienced by the participant after tasting a product. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 
| Number of subjects reporting mouth feel after administering each abrocitinib oral suspension formulation (F1-F6) in Part B | Mouth feel assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 
| Number of subjects reporting bitterness after administering each abrocitinib oral suspension formulation (F1-F6) in Part B | Bitterness assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 
| Number of subjects reporting tongue/mouth after administering each abrocitinib oral suspension formulation (F1-F6) in Part B | Tongue/mouth burn assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 
| Number of subjects reporting salty taste after administering each abrocitinib oral suspension formulation (F1-F6) in Part B | Salty taste assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 
| Number of subjects reporting sour taste after administering abrocitinib oral suspension formulation (F1-F6) in Part B | Sour taste assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulations (F1-F6) | 
| Number of subjects reporting sweet taste after administering abrocitinib oral suspension formulation (F1-F6) in Part B | Sweet taste assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire. | 1 (immediately after dosing), 5, 10, and 20 minutes after administering each abrocitinib oral suspension formulation (F1-F6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of metabolites (M1, M2 and M4) following the administration of 1×200 mg of abrocitinib tablet with or without famotidine 40 mg in Part A (AUCinf) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| PK parameters of metabolites (M1, M2 and M4) following the administration of 1×200 mg of abrocitinib tablet with or without famotidine 40 mg in Part A (Cmax) | Maximum observed plasma concentration. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| Number of subjects with treatment-emergent adverse event in Part A and Part B of the study |  | Baseline until Period 9 study day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abrocitinib, Atopic Dermatitis, Healthy Volunteers, Relative Bioavailability, Taste Assessment