Evaluation of the Pharmacokinetics, Safety and Tolerability of Single Dose of PF-06480605 in Chinese Healthy Participants

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY FOLLOWING SINGLE SUBCUTANEOUS DOSE OF PF-06480605 IN CHINESE HEALTHY PARTICIPANTS

This is a Phase 1, single-center, randomized, double-blind, third-party open (ie, participant blind, investigator blind and sponsor open), placebo controlled study to investigate PK, safety, tolerability, immunogenicity, and PD of PF 06480605 following a single subcutaneous dose of PF-06480605 450 mg and 150 mg (if needed) in Chinese healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Drug: 450mg; Drug: Placebo; Drug: 150mg

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female participants must be 18 to 45 years of age, inclusive, at the time of signing the ICD.
• Male and female Chinese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital sign and 12-lead ECG
• BMI of 19 to 27 kg/m2; and a total body weight >50 kg.

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).
• History of HIV infection, hepatitis B, hepatitis C or syphilis; positive testing for HIV, hepatitis B, HCVAb or serological reaction of syphilis.
• History of allergic or anaphylactic reaction to a therapeutic drug.
• History of recent active infections within 28 days prior to the screening visit.
• Participants with a fever within 48 hours prior to dosing.
• History of TB or active or latent or inadequately treated infection.
• Recent exposure to live vaccines within 28 days of the screening visit.
• A positive pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 12 participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment 450mg and placebo arms.	Drug: 450mg; following a single subcutaneous dose of PF-06480605 450 mg; Drug: Placebo; following a single subcutaneous dose of placebo
Experimental: Cohort 2; 12 participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment 150mg and placebo arms.	Drug: Placebo; following a single subcutaneous dose of placebo; Drug: 150mg; following a single subcutaneous dose of PF-06480605 150 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of PF-06480605	Cmax is the maximum observed plasma concentration.	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Time for Cmax (Tmax) of PF-06480605	Tmax is the time for Cmax.	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Area Under the Curve From Time 0 to End of Dosing Interval (AUC14day) of PF-06480605	AUC14day is area under the curve from time 0 to end of dosing interval (Day 14, 336 hours).	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, and 336 hours post dose on Day 1
Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06480605	AUCinf is area under the plasma concentration time profile from time 0 extrapolated to infinite time.	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Terminal Half-life (t1/2) of PF-06480605	t1/2 is the terminal half-life (time required for the plasma concentration to decline by 50%)	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and before the end of study (up to follow-up visits). AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.	Day 1 to Day 114
Number of Participants With Change From Baseline in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	Vital signs abnormalities included: supine diastolic blood pressure (BP) increase and decrease from BL of >=20mmHg or absolute value <50mmHg; systolic BP increase and decrease from BL of >=30mmHg or absolute value <90mmHg; pulse rate <40 or >120bpm.	From Baseline (BL) to Day 114
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	ECG assessments included PR, QT, and QTc intervals and QRS complex. ECG abnormalities included PR interval BL >200msec and max >=25% increase from BL, or BL <=200msec and max >=50% increase from BL, or absolute value >=300msec; QRS interval percent change from BL >=50% or absolute value >=140msec, QTcF change from BL >=30msec, or absolute value >450msec.	From BL to Day 114
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. Laboratory test abnormalities reported by at least 1 participant are reported in this outcome measure.	From BL to Day 114
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06480605	AUClast is area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Apparent Volume of Distribution (Vz/F) of PF-06480605	Vz/F is the apparent volume of distribution, defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Apparent Oral Clearance (CL/F) of PF-06480605	CL/F is the apparent oral clearance, which is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	At 0 (prior to dose), 2, 6, 24, 48, 72, 96, 216, 336, 672, 1008, 1344, 2016, and 2712 hours post dose on Day 1
Number of Participants With Positivie Anti-drug Antibody (ADA) Against PF-06480605	Summary of ADA incidence by visit is presented. ADA positive was defined as titer >=60.	On Days 1 (prior to dose), 15, 29, 57, 85 and 114
Number of Participants With Neutralizing Antibody (NAb) Against PF-06480605	Summary of NAb incidence by visit is presented. NAb positive was defined as titer >=5. ADA-positive participants (defined as titer >=60) were analyzed for NAb.	On Days 1 (prior to dose), 15, 29, 57, 85 and 114
Total Soluble Tumor Necrosis Factor Like Ligand 1A (sTL1A) Protein Concentration in Serum	The total sTL1A protein concentration in serum is summarized by time.	On Days 1 (prior to dose), 2, 5, 15, 29, 57, 85 and 114

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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): November 19, 2021
• Primary Completion (Actual): April 9, 2022
• Study Completion (Actual): April 9, 2022

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PK; IBD
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases
• Other Study ID Numbers: B7541013

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