Clinical Study to Evaluate Pharmacokinetics and Safety of PF-06700841 After Single and Multiple Oral Doses as Modified Release Formulations

A PHASE 1, OPEN-LABEL STUDY IN HEALTHY PARTICIPANTS TO INVESTIGATE THE PHARMACOKINETICS OF PF-06700841 FOLLOWING SINGLE ORAL ADMINISTRATION OF MODIFIED RELEASE FORMULATIONS UNDER FED AND FASTED CONDITIONS IN PART A AND A RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED STUDY TO EVALUATE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF-06700841 FOLLOWING MULTIPLE ORAL ADMINISTRATION OF MODIFIED RELEASE FORMULATION UNDER FASTED CONDITION IN PART B

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, and tolerability of PF-06700841 following single and multiple oral doses as modified release (MR) formulations in healthy, adult participants under fasted and fed conditions. The objective of Part A is to evaluate the relative bioavailability and food effect of 2 new MR formulations, MR1 and MR2. The objective of Part B is to evaluate the PK and safety/tolerability of MR3 formulation following multiple dose administration over a 7-day period. Overall, results from both parts will facilitate further development of an MR formulation for future clinical studies.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Other: Placebo; Drug: PF-06700841 IR; Drug: PF-06700841 MR1; Drug: PF-06700841 MR2; Drug: PF-06700841 MR3

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Quotient Sciences
    • Miami, Florida, United States, 33126
      • Quotient Sciences-Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female participants between 18 -55 years of age.
• BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
• Participants who are willing and able to comply with all scheduled visits, treatment
• plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Conditions that affect drug absorption (e.g., gastrectomy cholecystectomy)
• History of venous and arterial thrombosis (ie, deep venous thrombosis, pulmonary embolism) or hereditary clotting disorders (in first degree immediate relatives)
• Positive urine drug test.
• History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06700841: IR, MR1, MR2, MR1_fed; Participants receive single doses of immediate release (IR) followed by modified release (MR) MR1 and MR2, all in fasted condition followed by MR1 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841: MR1, MR2, IR, MR1_fed; Participants receive single doses of MR1 followed by MR2 and IR, all in fasted condition followed by MR1 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841: MR2, IR, MR1, MR1_fed; Participants receive single doses of MR2 followed by IR and MR1, all in fasted condition followed by MR1 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841: IR, MR1, MR2, MR2_fed; Participants receive single doses of IR followed by MR1 and MR1, all in fasted condition followed by MR2 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841: MR1, MR2, IR, MR2_fed; Participants receive single doses of MR1 followed by MR2 and IR, all in fasted condition followed by MR2 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841: MR2, IR, MR1, MR2_fed; Participants receive single doses of MR2 followed by IR and MR1, all in fasted condition followed by MR2 in fed condition in Periods 1-4	Drug: PF-06700841 IR; Immediate release formulation; Drug: PF-06700841 MR1; Modified release formulation 1; Drug: PF-06700841 MR2; Modified release formulation 2
EXPERIMENTAL: PF-06700841 MR3 (Dose A) or matching placebo; Participants receive dosing regimen 1 of MR3 (Dose A) or matching placebo for 7 days under fasted condition	Other: Placebo; Matching placebo; Drug: PF-06700841 MR3; Modified release formulation 3
EXPERIMENTAL: PF-06700841 MR3 (Dose B) or matching placebo; Participants receive dosing regimen 1 of MR3 (Dose B) or matching placebo for 7 days under fasted condition	Other: Placebo; Matching placebo; Drug: PF-06700841 MR3; Modified release formulation 3
EXPERIMENTAL: PF-06700841 MR3 (Dose C) or matching placebo; Participants receive dosing regimen 1 of MR3 (Dose C) or matching placebo for 7 days under fasted condition	Other: Placebo; Matching placebo; Drug: PF-06700841 MR3; Modified release formulation 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-06700841 in Part A	pre-dose, 1,2,4,6,8,10,12,16,24,36,48,72 hours post dose
Area under the plasma concentration-time curve from time zero to the last measured concentration (AUClast) of PF-06700841 in Part A	pre-dose, 1,2,4,6,8,10,12,16,24,36,48,72 hours post dose
Area under the plasma concentration-time curve from time zero to extrapolated infinite time (AUCinf) of PF-06700841 if data permit in Part A	pre-dose, 1,2,4,6,8,10,12,16,24,36,48,72 hours post dose
Time to reach maximum observed plasma concentration (Tmax) of PF-06700841 in Part A	pre-dose, 1,2,4,6,8,10,12,16,24,36,48,72 hours post dose
Number of participants with Treatment- Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation due to AEs in Part B	Baseline to Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with clinically relevant changes in Electrocardiogram (ECG) parameters in Part A	Pre-dose and 96 hours post dose
Number of subjects with clinically relevant changes in vital signs in Part A	Pre-dose and 96 hours post dose
Number of participants with clinically relevant changes in clinical laboratory tests in Part A	Baseline and 96 hours post dose
Number of participants with Treatment- Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation due to AEs in Part A	Baseline to Day 4
Maximum Observed Plasma Concentration (Cmax) of PF-06700841 in Part B on Day 1	pre-dose, 1,2,3,4,6,8,10,12,16 hours post dose on Day 1
Time to reach maximum observed plasma concentration (Tmax) of PF-06700841 in Part B on Day 1	pre-dose, 1,2,4,6,8,10,12,16 hours post dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of PF-06700841 in Part B on Day 7	pre-dose on Day 7, 1,2,3 4,6,8,12,16,24,48,72 hours post dose on Day 7
Time to reach maximum observed plasma concentration (Tmax) of PF-06700841 in Part B on Day 7	pre-dose on Day 7, 1,2,3 4,6,8,12,16,24,48,72 hours post dose on Day 7
Area under the plasma concentration-time curve from time zero to 24 hours (AUC24) of PF-06700841 in Part B on Day 1	pre-dose, 1,2,4,6,8,10,12,16 hours post dose on Day 1, pre-dose on Day 3 and Day 5, pre-dose on Day 7, 1,2,3,4,6,8,12,16,24,48,72 hours post dose on Day 7
Area under the plasma concentration-time curve from time zero to 24 hours (AUCtau) of PF-06700841 in Part B on Day 7	pre-dose, 1,2,4,6,8,10,12,16 hours post dose on Day 1, pre-dose on Day 3 and Day 5, pre-dose on Day 7, 1,2,3,4,6,8,12,16,24,48,72 hours post dose on Day 7
Terminal half-life of PF-06700841 in Part B	pre-dose, 1,2,4,6,8,10,12,16 hours post dose on Day 1, pre-dose on Day 3 and Day 5, pre-dose on Day 7, 1,2,3,4,6,8,12,16,24,48,72 hours post dose on Day 7

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 2, 2020
• Primary Completion (ACTUAL): January 11, 2021
• Study Completion (ACTUAL): January 11, 2021

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (ACTUAL): October 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; PF-06700841
• Other Study ID Numbers: B7931058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No