Clinical trial NCT04065633: Study of Commercial and Phase 3 of PF-04965842 Formulations, Estimation of Effect of Food on Commercial Formulation
Official title: A PHASE 1, OPEN LABEL, SINGLE-DOSE, CROSSOVER STUDY TO EVALUATE THE BIOEQUIVALENCE OF A COMMERCIAL TABLET FORMULATION OF PF-04965842 RELATIVE TO THE PHASE III TABLET FORMULATION UNDER FASTING CONDITIONS AND THE EFFECT OF FOOD ON THE RELATIVE BIOAVAILABILITY OF THE COMMERCIAL TABLET FORMULATION IN HEALTHY PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dermatitis, Atopic
Keywords: Phase 1 Bioequivalence Study
Healthy Participants
Estimation of the Effect of Food
Relative Bioavailability
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-08-22
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a Phase 1 randomized, open label, single-dose, crossover study in healthy participants to estimate the rBA of the commercial formulation of PF-04965842 (Test formulation 1) and the variant formulation with slower dissolution (Test formulation 2) compared to the Phase 3 formulation (Reference formulation), to demonstrate the BE of the commercial formulation relative to the Phase 3 formulation, and to estimate the effect of food on the rBA of the commercial formulation after a single 200 mg oral dose.
Primary purpose: OTHER

Brief summary: Part A

* To measure and compare the amount of study drug in the blood after a single 200 mg dose of study drug given as the commercial tablet formulation and the Phase 3 tablet formulation under fasting conditions
* To measure and compare the amount of study drug in the blood after a single 200 mg dose given as the variant Phase 3 tablet formulation and the Phase 3 tablet formulation under fasting conditions
* To estimate the effect of food on the amount of study drug in the blood after a single 200 mg dose of the commercial formulation

Part B

• To measure and compare the amount of study drug in the blood after a single 200 mg dose given as the commercial tablet formulation and the Phase 3 tablet formulation under fasting conditions

Parts A \& B

* To collect samples for genotyping (CYP2C19 and CYP2C9 - enzymes that metabolize \[break down\] certain medications)

  o Genotyping is the collection of a small sample of blood that contains your genes
* To evaluate the safety and tolerability of the study drug after single 200 mg doses of the three different formulations given to healthy participants
* To measure the amount of study drug in the blood after single doses of the different formulations
* To collect exploratory samples for biobanking o Biobanking is the collection and storage of blood samples for possible future testing

Detailed description: The purpose of this study in healthy participants is to estimate the bioavailability (BA) of the commercial formulation of PF-04965842 and a variant formulation with slower dissolution relative to the Phase 3 formulation, to demonstrate the bioequivalence (BE) of the commercial formulation relative to the Phase 3 formulation, and to estimate the effect of food on the BA of the commercial formulation. This study consists of 2 parts: Part A is to estimate the relative BA (rBA) of single 200 mg doses of the commercial tablet formulation of PF-04965842 and a variant formulation of slower dissolution rate compared to the Phase 3 tablet formulation. The effect of food on the BA of the commercial tablet formulation will also be evaluated. Part B is to establish BE between the Phase 3 and commercial formulations. The study will follow a staged approach as the sample size for BE cannot be determined with currently available information.

Therefore, it is proposed to assess the maximum observed concentration (Cmax) and area under the curve (AUC) ratios between the Phase 3 and commercial formulations as well as the within-participant variability of Cmax and AUC values determined in Part A. Based on the results from Part A, the sample size of Part B will be determined and the decision to proceed to Part B will be made.

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb)

Exclusion Criteria:

* Any condition possibly affecting drug absorption (eg, gastrectomy).

  * History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis
  * Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) .History of tuberculosis (TB) (active or latent) or inadequately treated TB infection.
  * History of chronic infections, history of recurrent infections, history of latent infections, .History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
  * history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ

Primary outcomes:
measure: Plasma PF-04965842 PK parameters
timeFrame: hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose
measure: Plasma PF-04965842 PK parameters
timeFrame: hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose
Secondary outcomes:
measure: number of subjects with treatment-emergent adverse event
timeFrame: baseline until Period 4 study day 35
measure: number of subjects with significant change from baseline in Supine Blood pressure, pulse rate and oral temperature
timeFrame: baseline until Period 4 study day 3
measure: number of subjects with significant Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR
timeFrame: baseline until Period 4 study day 3
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
affiliation: Pfizer
name: Sylvester Pawlak, APRN
role: PRINCIPAL_INVESTIGATOR
References: