Dose Escalation Study of PF-06741086 In Healthy Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: PF-06741086
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, tolerability, pharmacokinetics, pharmacodynamics, Phase 1, first in human, monoclonal antibody, tissue factor pathway inhibitor, japanese