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

Pfizer12 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Inflammatory Bowel Disease

Interventions

450mgDRUG

following a single subcutaneous dose of PF-06480605 450 mg

150mgDRUG

following a single subcutaneous dose of PF-06480605 150 mg

PlaceboDRUG

following a single subcutaneous dose of placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Peking University Third Hospital

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

Maximum Observed Concentration (Cmax) of PF-06480605

Cmax is the maximum observed plasma concentration.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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%)

Time frame: 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 Outcomes

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.

Data from ClinicalTrials.gov

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Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: On Days 1 (prior to dose), 2, 5, 15, 29, 57, 85 and 114