Pharmacokinetic Study Comparing Hercules, EU-approved Herceptin® and US-Licensed Herceptin® Administered as a Single Intravenous Infusion to Healthy Male Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Mylan Pharmaceuticals Inc
- Enrollment
- 132
- Primary Endpoint
- Peak Plasma Concentration (Cmax)
Study Overview
Brief Summary
The primary objective of this study was to demonstrate pharmacokinetic similarity of Mylan trastuzumab (Hercules) versus EU-approved Herceptin® and US-licensed Herceptin® and pharmacokinetic similarity of EU-approved Herceptin® versus US-licensed Herceptin® after 8 mg/kg as single dose administered as intravenous infusion over 90 minutes in healthy male subjects based on the equivalence criterion that AUC0-∞, AUC0-last, and Cmax least square mean ratios are bounded within the 90% confidence intervals, 80.00% - 125.00%. Three similarity assessments were performed, 1) Hercules vs. EU-approved Herceptin®, 2) Hercules vs. US-licensed Herceptin® and 3) EU-approved Herceptin® vs. US-licensed Herceptin®. Secondary objectives included further pharmacokinetic assessment of similarity of Hercules, EU-approved Herceptin® and US-licensed Herceptin® λz, tmax and t1/2 along with assessment of safety (including immunogenicity) and local tolerance.
Detailed Description
All subjects checked into the clinical facility on the day prior to dosing. On study day 1, each subject received either a single i.v. infusion of 8 mg/kg BW in 250 mL normal saline over a 90 minute period of Mylan trastuzumab (Hercules), EU-approved Herceptin®, or US-licensed Herceptin®. Dosing occurred following an overnight fast of at least 8 hours. On the day of dosing, subjects fasted for the first 3 hours after the start of the infusion then received standard meals approximately 3, 6 and 9 hours post-dose. In each study period, blood samples were collected just immediately prior to dose administration (0 hour) and at 45 and 90 minutes (just prior to end of infusion). Blood samples were collected post-dose at 3, 6, 9, 24 and 48 hours, relative to the start of infusion. The subjects were allowed to leave the clinical facility after the 48-hour blood sample collection. Subjects returned to the clinical facility for the scheduled blood sample collections post-dose on Day 5, 8, 11, 15, 22, 29, 43, 57, and 71. Serum samples were stored at -80°C ± 15°C until shipment for analysis. Blood samples for anti-drug antibodies (ADA) were collected prior to dosing on Day 1 and on Day 71. Blood samples for C-reactive protein (CRP) were obtained at Screening, prior to dosing and at 3, 24 and 48 hours post-dose and on Day 8 and 71. Blood samples for analysis of immunoglobulins were collected prior to dosing on Day 1 and on Day 8 and 71.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •healthy adult subjects, age 18 to 55 years old
- •able to understand procedures, agree to participate and willing to give informed consent
Exclusion Criteria
- •history of any significant disease
- •use of any medication 7 days prior to start of study
- •participation in a clinical trial within 30 days of start of study
Outcomes
Primary Outcomes
Peak Plasma Concentration (Cmax)
Time Frame: 71 days
The primary pharmacokinetic variables for assessment of bioequivalence are dose-normalized Cmax based on the equivalence criterion that Cmax least square mean ratios are bounded within the 90% confidence intervals, 80.00% - 125.00%.
Area Under the Plasma Concentration Versus Time Curve (AUC) - Time 0 to Last Blood Draw (AUC0-last)
Time Frame: 71 days
The primary pharmacokinetic variables for assessment of bioequivalence are dose-normalized AUC0-last based on the equivalence criterion that AUC0-last least square mean ratios are bounded within the 90% confidence intervals, 80.00% - 125.00%.
Area Under the Plasma Concentration Versus Time Curve (AUC) - Time 0 to Infinity AUC0-∞)
Time Frame: 71 days
The primary pharmacokinetic variables for assessment of bioequivalence are dose-normalized AUC0-∞, based on the equivalence criterion that AUC0-∞ least square mean ratios are bounded within the 90% confidence intervals, 80.00% - 125.00%.
Secondary Outcomes
- Monitoring of Heart Function (ECG and Echocardiography)(71 days)
- Measurement of C-reactive Protein(71 days)
- Incidence of Treatment-Emergent Adverse Events (AEs)(71 days)
- Local Infusion Tolerance(71 days)
- Immunogenicity(71 days)