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.
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT04903093
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part B: Abrocitinib Suspension F2 Abrocitinib Suspension F2 - Part B: Abrocitinib Suspension F5 Abrocitinib Suspension F5 - Part B: Abrocitinib Suspension F3 Abrocitinib Suspension F3 - Part B: Abrocitinib Suspension F4 Abrocitinib Suspension F4 - Part B: Abrocitinib Suspension F6 Abrocitinib Suspension F6 - Part B: Abrocitinib Suspension F6 + Famotidine Abrocitinib Suspension F6 - Part B: Abrocitinib Suspension F1 + Famotidine Abrocitinib Suspension F1 - Part B: Abrocitinib Suspension F5 + Famotidine Abrocitinib Suspension F5 - Part A: Abrocitinib Tablet Abrocitinib tablet - Part B: Abrocitinib Suspension F1 Abrocitinib Suspension F1 - Part B: Abrocitinib Suspension F2 + Famotidine Abrocitinib Suspension F2 - Part A: Abrocitinib Suspension F1 Abrocitinib Suspension F1 - Part B: Abrocitinib Suspension F3 + Famotidine Abrocitinib Suspension F3 - Part B: Abrocitinib Suspension F4 + Famotidine Abrocitinib Suspension F4 - Part B: Abrocitinib Suspension F3 + Famotidine Famotidine - Part B: Abrocitinib Suspension F4 + Famotidine Famotidine - Part A: Abrocitinib Tablet + Famotidine Famotidine - Part B: Abrocitinib Suspension F1 + Famotidine Famotidine - Part B: Abrocitinib Suspension F2 + Famotidine Famotidine - Part B: Abrocitinib Suspension F5 + Famotidine Famotidine - Part B: Abrocitinib Suspension F6 + Famotidine Famotidine -
- Primary Outcome Measures
Name Time Method AUCinf of Abrocitinib Following the Administration of Abrocitinib Commercial Tablet, Abrocitinib Oral Suspension Formulation 1 or Famotidine Plus Abrocitinib Commerical Tablet 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. Area under the plasma concentration time profile from time 0 extrapolated to infinity (AUCinf) was measured. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Cmax of Abrocitinib Following the Administration of Abrocitinib Commercial Tablet, Abrocitinib Oral Suspension Formulation 1 or Famotidine Plus Abrocitinib Commerical Tablet 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. Maximum observed plasma concentration (Cmax) was measured. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Assessment of Overall Liking After Administering Each Abrocitinib Oral Suspension Formulation (Formulation [F]1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Mouth Feel After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Bitterness After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Tongue/Mouth Burn After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Salty Taste After Administering Each Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Sour Taste After Administering Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
Assessment of Sweet Taste After Administering Abrocitinib Oral Suspension Formulation (F1-F6) in Part B 0 Hours, 5, 10, 20 min after swallowing the suspension on Day 1 of each period. For the taste assessment in Part B of the study, the data used in the analysis was transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.
- Secondary Outcome Measures
Name Time Method 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 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. Area under the plasma concentration time profile from time 0 extrapolated to infinity.
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 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. Area under the plasma concentration time profile from time 0 extrapolated to infinity.
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 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. Area under the plasma concentration time profile from time 0 extrapolated to infinity.
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 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. Maximum observed plasma concentration.
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 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. Maximum observed plasma concentration.
Number of Participants With Nausea AEs Baseline up to follow-up (Day 36) Number of participants who received abrocitinib 200 mg alone and who received abrocitinib 200 mg plus famotidine 40 mg and had nausea AEs were reported.
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 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. Maximum observed plasma concentration.
Number of Participants With Treatment-Emergent Adverse Event Baseline up to follow-up (Day 36) Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product, without regard to relatedness. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study intervention. Relatedness to study intervention was determined by the investigator.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) Baseline up to follow-up (Day 36) Participants with laboratory abnormalities (without regard to baseline abnormality) were reported.
Number of Participants With Clinically Significant Vital Sign Values Baseline up to follow-up (Day 36) Participants with clinically significant vital sign values were reported.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values Baseline up to follow-up (Day 36) Participants with clinically significant abnormal ECG values were reported.
Trial Locations
- Locations (1)
New Haven Clinical Research Unit
🇺🇸New Haven, Connecticut, United States