A Study to Evaluate the PF-06700841 Effect on QTc Interval in Healthy Volunteers

A PHASE 1, RANDOMIZED, PLACEBO-AND POSITIVE-CONTROLLED CROSSOVER STUDY TO DETERMINE THE EFFECT OF SINGLE-DOSE PF-06700841 ON QTC INTERVAL IN HEALTHY VOLUNTEERS

A phase 1, 6-sequence, 3-period, subject- and investigator blinded and sponsor-open, crossover study in healthy volunteers to evaluate the PF-06700841 effect on QTc interval. Each subject randomized will receive placebo, PF-06700841 200 mg and moxifloxacin (open label) in one of the 6 sequences. Moxifloxacin is positive control to demonstrate the study sensitivity and PF-06700841 effect on QTc will be assessed by concentration-QT analysis

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06700841; Drug: Placebo; Drug: moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy female subjects of non-childbearing potential and/or male subjects. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including BP and pulse rate measurement, 12-lead ECG, or clinical laboratory tests.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb) at screening.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic (including alcoholic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and hereditary liver diseases), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)
• Self-reported history or risk factors for QT prolongation or torsades de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesaemia, congenital long QT syndrome, myocardial ischemia or infarction), congenital deafness, family history of sudden death, and family history of long QT syndrome.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product (whichever is longer)
• Subjects with known prior participation (ie, randomized and received at least 1 dose of investigational product) in a trial involving PF-06700841
• History of tuberculosis or active or latent or inadequately treated infection, positive QuantiFERON- tuberculosis (TB) Gold test
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb)
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Seq 1; PF-06700841-> placebo-> moxifloxacin	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin
Experimental: Seq 2; PF-06700841->moxifloxacin->placebo	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin
Experimental: Seq 3; Placebo->PF-06700841->moxifloxacin	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin
Experimental: Seq 4; Placebo->moxifloxacin->PF-06700841	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin
Experimental: Seq 5; Moxifloxacin->PF-06700841->placebo	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin
Experimental: Seq 6; Moxifloxacin->placebo->PF-06700841	Drug: PF-06700841; a single oral dose of 200 mg PF-06700841; Drug: Placebo; Placebo matching PF-06700841; Drug: moxifloxacin; a single oral dose of 400 mg moxifloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc change from baseline following PF-06700841 treatment	QTc change from baseline at geometric mean of maximum concentrations observed after single doses of 200 mg PF-06700841 and maximum concentrations expected at lower doses of 30 and 60 mg.	0 to 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc change from baseline following moxifloxacin treatment	QTc change from baseline at 3 hours (Tmax) after a single dose of 400 mg moxifloxacin administration	0-48 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hughes JH, Qiu R, Banfield C, Dowty ME, Nicholas T. Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients. Clin Pharmacol Drug Dev. 2022 Aug 31. doi: 10.1002/cpdd.1163. [Epub ahead of print]

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Actual): February 6, 2019
• Study Completion (Actual): February 6, 2019

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: PF-06700841; QT effect; concentration-QTc analysis
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Moxifloxacin; PF-06700841
• Other Study ID Numbers: B7931019; 2018-001932-23 (EudraCT Number)

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