Clinical trial NCT02531815: Dose Escalation Study of PF-06741086 In Healthy Subjects
Official title: A Randomized, Double-blind, Sponsor-open, Placebo-controlled, Single Intravenous Or Subcutaneous Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-06741086 In Healthy Subjects And An Open-label Evaluation In Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: safety
tolerability
pharmacokinetics
pharmacodynamics
Phase 1
first in human
monoclonal antibody
tissue factor pathway inhibitor
japanese
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-08-25
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: BASIC_SCIENCE

Brief summary: This Phase 1 first-in-human single ascending dose study will be a randomized, double-blind, placebo-controlled investigation of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06741086.


Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs) and 100 kg (220 lbs).

Exclusion Criteria:

* Increased risk of thrombosis (coronary artery disease, hypercholesterolemia, diabetes)
* Use of nicotine/tobacco products
* Clotting disorders

Primary outcomes:
measure: Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
timeFrame: Day 1 up to Day 84
measure: Percentage of subjects with laboratory abnormalities
timeFrame: Day 1 up to Day 84
measure: Number of subjects with change from baseline in vital signs
timeFrame: Day 1 up to Day 84
measure: Number of subjects with change from baseline in electrocardiogram (ECG) parameters
timeFrame: Day 1 to Day 84
measure: Percentage of subjects with changes from baseline in physical examination
timeFrame: Day 1 to Day 84
measure: Percentage of subjects with infusion site reactions
timeFrame: Day 1 up to Day 7
measure: Percentage of subjects with injection site reactions
timeFrame: Day 1 to Day 7
Secondary outcomes:
measure: Plasma PF-06741086 concentrations
timeFrame: Day 1 up to Day 84
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 up to Day 84
measure: Time for Cmax (Tmax)
timeFrame: Day 1 up to Day 84
measure: Area under the curve from time zero to last quantifiable concentration (AUClast)
timeFrame: Day 1 up to Day 84
measure: Terminal half-life (t 1/2)
timeFrame: Day 1 up to Day 84
measure: Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf)
timeFrame: Day 1 up to Day 84
measure: Volume of distribution at steady state (Vss)
timeFrame: Day 1 up to Day 84
measure: Apparent volume of distribution (Vz/F)
timeFrame: Day 1 up to Day 84
measure: Clearance (CL)
timeFrame: Day 1 up to Day 84
measure: Apparent clearance (CL/F)
timeFrame: Day 1 up to Day 84
measure: Bioavailability (F) [F = AUC (inf,sc) / AUC (inf,iv)]
timeFrame: Day 1 up to Day 84
measure: Mean residence time (MRT)
timeFrame: Day 1 up to Day 84
measure: Total tissue factor pathway inhibitor concentrations over time
timeFrame: Day 1 up to Day 84
measure: Thrombin generation
timeFrame: Day 1 up to Day 84
measure: Prothrombin fragment 1+2 (PF1+2) concentrations over time
timeFrame: Day 1 up to Day 84
measure: D-dimer concentrations over time
timeFrame: Day 1 up to Day 84
measure: Dilute prothrombin time (dPT)
timeFrame: Day 1 up to Day 84
measure: Frequency of anti-drug antibody (ADA) and neutralizing antibody (NAb) production
timeFrame: Day 1 up to Day 84
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: