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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05107492

Enrollment

Registered

2021-11-04

Start date

2021-11-19

Completion date

2022-04-09

Last updated

2024-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inflammatory Bowel Disease

Keywords

IBD, PK

Brief summary

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.

Interventions

DRUG450mg

following a single subcutaneous dose of PF-06480605 450 mg

DRUG150mg

following a single subcutaneous dose of PF-06480605 150 mg

DRUGPlacebo

following a single subcutaneous dose of placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Apparent Volume of Distribution (Vz/F) of PF-06480605	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	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.
Apparent Oral Clearance (CL/F) of PF-06480605	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	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Day 1 to Day 114	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.
Number of Participants With Neutralizing Antibody (NAb) Against PF-06480605	On Days 1 (prior to dose), 15, 29, 57, 85 and 114	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.
Total Soluble Tumor Necrosis Factor Like Ligand 1A (sTL1A) Protein Concentration in Serum	On Days 1 (prior to dose), 2, 5, 15, 29, 57, 85 and 114	The total sTL1A protein concentration in serum is summarized by time.
Number of Participants With Positivie Anti-drug Antibody (ADA) Against PF-06480605	On Days 1 (prior to dose), 15, 29, 57, 85 and 114	Summary of ADA incidence by visit is presented. ADA positive was defined as titer \>=60.
Number of Participants With Change From Baseline in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	From Baseline (BL) to Day 114	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.
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	From BL to Day 114	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.
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline Abnormality)	From BL to Day 114	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.
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06480605	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	AUClast is area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration

Countries

China

Participant flow

Recruitment details

A total of 12 Chinese healthy adult participants were enrolled, with 9 assigned to PF-06480605 450mg group and 3 to placebo.

Pre-assignment details

This was a placebo-controlled study of PF-06480605 following 450 mg and 150 mg (if needed) in Chinese healthy adults. Optional 150 mg cohort was not conducted as pharmacokinetic (PK) data of 450mg group did not suggest ethnic difference with previous Western/Japanese studies (by comparing dose-normalized mean exposures/dose-normalized mean concentrations profiles).

Participants by arm

Arm	Count
PF-06480605 450mg Participants received a single subcutaneous dose of PF-06480605 450 mg on Day 1.	9
Placebo Participants received matching placebo on Day 1.	3
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	0

Baseline characteristics

Characteristic	PF-06480605 450mg	Placebo	Total
Age, Continuous	34 Years	28 Years	34 Years
Age, Customized <18	0 Participants	0 Participants	0 Participants
Age, Customized 18-44	9 Participants	3 Participants	12 Participants
Age, Customized 45-64	0 Participants	0 Participants	0 Participants
Age, Customized >=65	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian (Chinese)	9 Participants	3 Participants	12 Participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants
Sex: Female, Male Male	8 Participants	2 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 3
other Total, other adverse events	7 / 9	3 / 3
serious Total, serious adverse events	0 / 9	0 / 3

Outcome results

Primary

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

Population: The PK parameter analysis population was defined as all randomized participants who received at least 1 dose of study intervention and for whom at least 1 of the PK parameters of interest was calculated. Data for this OM was not planned to be collected and analyzed for placebo arm.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-06480605 450mg	Area Under the Curve From Time 0 to End of Dosing Interval (AUC14day) of PF-06480605	11600000 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 26

Primary

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.