A Pharmacokinetic Study Comparing PF-06439535 And Bevacizumab In Healthy Male Volunteers (REFLECTIONS B739-01)

Study Overview
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Brief Summary
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This study is to prove that the handling (also referred to as pharmacokinetics) of the following drugs PF-06439535, Avastin® (bevacizumab) that is licensed for use in the United States (bevacizumab-US) and Avastin® (bevacizumab) obtained from Europe (bevacizumab-EU) is similar in healthy male volunteers after receiving a single intravenous dose of either drugs. During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms of PF-06439535, bevacizumab-US and bevacizumab-EU. Safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.

Official Title
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Phase 1, Double Blind, Randomized, Parallel-Group, Single-Dose, 3-Arm, Comparative Pharmacokinetic Study Of PF-06439535 And Bevacizumab Sourced From US And EU Administered To Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: PF-06439535
* Biological: Avastin
* Biological: Avastin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects 21-55 years old Subjects who have previously been exposed to a biologic agent (other than a VEGF [Vascular Endothelial Growth Factor Receptor] inhibitor) may enroll provided that at least 3 months have passed since the last administration of that drug Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50kg (110lbs) Exclusion Criteria: Evidence or history of a clinically significant disease or clinical finding at Screening Previous treatment with an anti-VEGF antibody, or any other antibody or protein targeting the VEGF receptor.

Ages Eligible for Study
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Minimum Age: 21 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
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A = PF-06439535<br>Intervention Description: Sterile vial 400mg, single-dose 5mg/kg administered as 90-minute infusion on day 1. | Biological: PF-06439535<br>* Solution for intravenous infusion, single dose of 5mg/kg, administered as 90-minute infusion.<br>* Other names: PF-06439535, a potential biosimilar to bevacizumab;|
| Active Comparator: B = Bevacizumab-EU<br>Intervention Description: Sterile vial 400mg, single-dose 5mg/kg administered as 90-minute infusion on day 1. | Biological: Avastin<br>* Solution for intravenous infusion, single dose of 5mg/kg, administered as 90-minute infusion.<br>* Other names: Bevacizumab (European Union);|
| Active Comparator: C = Bevacizumab-US<br>Intervention Description: Sterile vial 400mg, single-dose 5mg/kg administered as 90-minute infusion on day 1. | Biological: Avastin<br>* Solution for intravenous infusion, single dose of 5mg/kg, administered as 90-minute infusion.<br>* Other names: Bevacizumab (United States);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Day 1 - Day 71 | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) |  | Day 1 - Day 71 | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). | Day 1 - Day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Clearance (CL) |  | Day 1 - Day 71 | 
| Terminal Disposition Half-Life (t1/2) |  | Day 1 - Day 71 | 
| Volume of Distribution at Steady State (Vss) |  | Day 1 - Day 71 | 
| Incidence of anti-bevacizumab antibodies (ADA), including neutralizing antibodies (Nab) |  | Day 1 - Day 71 or LSLV, whichever occurs later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Biosimilarity, Similarity, PK, Phase 1, Bevacizumab, Healthy Volunteers, Single-Dose, Oncology