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.

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Abrocitinib Suspension F4; Drug: Abrocitinib Suspension F3; Drug: Abrocitinib Suspension F5; Drug: Abrocitinib Suspension F1; Drug: Famotidine; Drug: Abrocitinib Suspension F2; Drug: Abrocitinib Suspension F6; Drug: Abrocitinib tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT04903093

B7451061

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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19 participants in 15 patient groups

Part A: Abrocitinib Tablet

Experimental group

Treatment:

Drug: Abrocitinib tablet

Part A: Abrocitinib Suspension F1

Experimental group

Treatment:

Drug: Abrocitinib Suspension F1

Part A: Abrocitinib Tablet + Famotidine

Experimental group

Treatment:

Drug: Famotidine

Part B: Abrocitinib Suspension F1

Experimental group

Treatment:

Drug: Abrocitinib Suspension F1

Part B: Abrocitinib Suspension F2

Experimental group

Treatment:

Drug: Abrocitinib Suspension F2

Part B: Abrocitinib Suspension F3

Experimental group

Treatment:

Drug: Abrocitinib Suspension F3

Part B: Abrocitinib Suspension F4

Experimental group

Treatment:

Drug: Abrocitinib Suspension F4

Part B: Abrocitinib Suspension F5

Experimental group

Treatment:

Drug: Abrocitinib Suspension F5

Part B: Abrocitinib Suspension F6

Experimental group

Treatment:

Drug: Abrocitinib Suspension F6

Part B: Abrocitinib Suspension F1 + Famotidine

Experimental group

Treatment:

Drug: Famotidine

Drug: Abrocitinib Suspension F1

Part B: Abrocitinib Suspension F2 + Famotidine

Experimental group

Treatment:

Drug: Abrocitinib Suspension F2

Drug: Famotidine

Part B: Abrocitinib Suspension F3 + Famotidine

Experimental group

Treatment:

Drug: Famotidine

Drug: Abrocitinib Suspension F3

Part B: Abrocitinib Suspension F4 + Famotidine

Experimental group

Treatment:

Drug: Famotidine

Drug: Abrocitinib Suspension F4

Part B: Abrocitinib Suspension F5 + Famotidine

Experimental group

Treatment:

Drug: Famotidine

Drug: Abrocitinib Suspension F5

Part B: Abrocitinib Suspension F6 + Famotidine

Experimental group

Treatment:

Drug: Abrocitinib Suspension F6

Drug: Famotidine