A Pharmacokinetic Study Comparing PF-05280014 And Trastuzumab In Healthy Male Volunteers (REFLECTIONS B327-01)

Study Overview
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Brief Summary
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In this study, healthy male volunteers will receive a single intravenous administration of either PF-05280014 or trastuzumab (United States) or trastuzumab (European Union). During the course of the study, the 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-05280014 and the US-licensed and EU-approved trastuzumab products. Safety, tolerability, and immunologic response also will 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-05280014 And Trastuzumab Sourced From US And EU Administered To Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: PF-05280014
* Biological: Herceptin
* Biological: Herceptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight > 50 kg (110 lbs). Male subjects must agree that they and their female spouse/partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non-childbearing potential. Left ventricular ejection fraction (LVEF) within the normal range as measured by echocardiogram (ECHO) within 8 weeks prior to randomization. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease, or clinical findings at screening excluding untreated, asymptomatic seasonal allergies at time of dosing. Clinically significant abnormalities in laboratory test results. Previous exposure to a monoclonal antibody or current use of other biologics. History of allergic or anaphylactic reaction to a therapeutic drug or benzyl alcohol. Use of prescription or non prescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements must be discontinued 28 days prior to the first dose of study medication. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

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
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>PF-05280014 | Biological: PF-05280014<br>* Concentrate for solution for infusion, sterile vial 150 mg, single-dose 6 mg/kg administered as 90-minute infusion on day 1<br>* Other names: Trastuzumab-Pfizer;|
| Active Comparator: B<br>Trastuzumab-EU | Biological: Herceptin<br>* Concentrate for solution for infusion, sterile vial 150 mg, single-dose 6 mg/kg administered as 90-minute infusion on day 1<br>* Other names: Trastuzumabum (European Union);|
| Active Comparator: C<br>Trastuzumab-US | Biological: Herceptin<br>* Concentrate for solution for infusion, sterile vial 440 mg, single-dose 6 mg/kg administered as 90-minute infusion on day 1<br>* Other names: Trastuzumab (United States);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of PF-05280014 compared to trastuzumab-EU. |  | Day 1 - Day 71 | 
| Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of PF-05280014 compared to trastuzumab-US. |  | Day 1 - Day 71 | 
| Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of trastuzumab-EU to trastuzumab-US. |  | Day 1 - Day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-trastuzumab antibodies (ADAs), including neutralizing antibodies (Nab). |  | Day 1 - LSLV or Day 71 whichever occurs later | 
| Pharmacokinetic parameters Maximal Concentration (Cmax) and Area-Under-the-Curve (AUC) for the combined groups of trastuzumab-US and trastuzumab EU. |  | Day 1 - Day 71 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER-2, Oncology, Bioequivalence, Biosimilarity, Similarity, PK, Phase I, Trastuzumab, Healthy Male Volunteers, Single-dose