Healthy
Conditions
Keywords
safety, tolerability, pharmacokinetics, pharmacodynamics, Phase 1, first in human, monoclonal antibody, tissue factor pathway inhibitor, japanese
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.
Interventions
BIOLOGICALPF-06741086
PF-06741086, single dose, beginning with Cohort 1 dose level at 30 mg. Subsequent dose levels will be determined after data review of prior cohort(s)
DRUGPlacebo
Placebo for PF-06741086, single dose
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs | Day 1 up to Day 84 | — |
| Percentage of subjects with laboratory abnormalities | Day 1 up to Day 84 | — |
| Number of subjects with change from baseline in vital signs | Day 1 up to Day 84 | blood pressure, pulse rate, temperature, respiration rate |
| Number of subjects with change from baseline in electrocardiogram (ECG) parameters | Day 1 to Day 84 | — |
| Percentage of subjects with changes from baseline in physical examination | Day 1 to Day 84 | — |
| Percentage of subjects with infusion site reactions | Day 1 up to Day 7 | — |
| Percentage of subjects with injection site reactions | Day 1 to Day 7 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | Day 1 up to Day 84 | — |
| Time for Cmax (Tmax) | Day 1 up to Day 84 | — |
| Area under the curve from time zero to last quantifiable concentration (AUClast) | Day 1 up to Day 84 | — |
| Terminal half-life (t 1/2) | Day 1 up to Day 84 | — |
| Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf) | Day 1 up to Day 84 | — |
| Apparent volume of distribution (Vz/F) | Day 1 up to Day 84 | Subcutaneous administration only |
| Thrombin generation | Day 1 up to Day 84 | may include lag time, peak thrombin generation, and endogenous thrombin generation potential |
| Prothrombin fragment 1+2 (PF1+2) concentrations over time | Day 1 up to Day 84 | — |
| D-dimer concentrations over time | Day 1 up to Day 84 | — |
| Dilute prothrombin time (dPT) | Day 1 up to Day 84 | — |
| Frequency of anti-drug antibody (ADA) and neutralizing antibody (NAb) production | Day 1 up to Day 84 | Immunogenicity |
| Volume of distribution at steady state (Vss) | Day 1 up to Day 84 | Intravenous administration only |
| Clearance (CL) | Day 1 up to Day 84 | Intravenous administration only |
| Apparent clearance (CL/F) | Day 1 up to Day 84 | Subcutaneous administration only |
| Bioavailability (F) [F = AUC (inf,sc) / AUC (inf,iv)] | Day 1 up to Day 84 | — |
| Mean residence time (MRT) | Day 1 up to Day 84 | — |
| Total tissue factor pathway inhibitor concentrations over time | Day 1 up to Day 84 | — |
| Plasma PF-06741086 concentrations | Day 1 up to Day 84 | — |
Countries
Belgium
Outcome results
None listed