Clinical trial NCT01603264: A Pharmacokinetic Study Comparing PF-05280014 And Trastuzumab In Healthy Male Volunteers (REFLECTIONS B327-01)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Bioequivalence
Biosimilarity
Similarity
PK
Phase I
Trastuzumab
Healthy Male Volunteers
Single-dose
HER-2
Oncology
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-05-22
Enrollment: 105
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of PF-05280014 compared to trastuzumab-EU.
timeFrame: Day 1 - Day 71
measure: Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of PF-05280014 compared to trastuzumab-US.
timeFrame: Day 1 - Day 71
measure: Pharmacokinetic parameters Area-Under-the-Curve (AUC) and Maximal Concentration (Cmax) of trastuzumab-EU to trastuzumab-US.
timeFrame: Day 1 - Day 71
Secondary outcomes:
measure: Incidence of anti-trastuzumab antibodies (ADAs), including neutralizing antibodies (Nab).
timeFrame: Day 1 - LSLV or Day 71 whichever occurs later
measure: Pharmacokinetic parameters Maximal Concentration (Cmax) and Area-Under-the-Curve (AUC) for the combined groups of trastuzumab-US and trastuzumab EU.
timeFrame: Day 1 - Day 71
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Yin D, Barker KB, Li R, Meng X, Reich SD, Ricart AD, Rudin D, Taylor CT, Zacharchuk CM, Hansson AG. A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01). Br J Clin Pharmacol. 2014 Dec;78(6):1281-90. doi: 10.1111/bcp.12464.