Dose Escalation Study of PF-06741086 In Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: PF-06741086; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (subcutaneous [SC]) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 2 (SC) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 3 (SC) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 4 (Intravenous [IV]) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 5 (IV) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 6 (IV) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 7 (IV) PF-06741086, Placebo	Biological: PF-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); Drug: Placebo; Placebo for PF-06741086, single dose; Other Names: saline placebo
Experimental: Cohort 8 (subcutaneous [SC]) PF-06741086	Biological: PF-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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	blood pressure, pulse rate, temperature, respiration rate	Day 1 up to Day 84
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma PF-06741086 concentrations		Day 1 up to Day 84
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
Volume of distribution at steady state (Vss)	Intravenous administration only	Day 1 up to Day 84
Apparent volume of distribution (Vz/F)	Subcutaneous administration only	Day 1 up to Day 84
Clearance (CL)	Intravenous administration only	Day 1 up to Day 84
Apparent clearance (CL/F)	Subcutaneous administration only	Day 1 up to Day 84
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
Thrombin generation	may include lag time, peak thrombin generation, and endogenous thrombin generation potential	Day 1 up to Day 84
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	Immunogenicity	Day 1 up to Day 84

Collaborators and Investigators

• Sponsor: 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: August 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 3, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (Estimate): August 25, 2015

Study Record Updates

• Last Update Posted (Estimate): August 12, 2016
• Last Update Submitted That Met QC Criteria: August 10, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; monoclonal antibody; Phase 1; pharmacodynamics; tissue factor pathway inhibitor; first in human; japanese
• Other Study ID Numbers: B7841001; 2015-001821-17 (EudraCT Number)