Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion

October 30, 2015 updated by: Mylan Pharmaceuticals Inc

Pharmacokinetic Study Comparing Hercules, EU-approved Herceptin® and US-Licensed Herceptin® Administered as a Single Intravenous Infusion to Healthy Male Volunteers

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

132

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment A
Hercules: 8 mg/kg i.v. infusion over 90 minutes
Biological: Hercules
Powder Concentrate for Intravenous Infusion, 150 mg/vial
Other Names:
  • Trastuzumab
Active Comparator: Treatment B
Herceptin EU: 8 mg/kg i.v. infusion over 90 minutes
Biological: Herceptin EU
Powder for Concentrate for Solution for Infusion, 150 mg/vial
Other Names:
  • Trastuzumab
Active Comparator: Treatment C
Herceptin US: 8 mg/kg i.v. infusion over 90 minutes
Biological: Herceptin US
Intravenous Infusion, 440 mg/vial
Other Names:
  • Trastuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%.
71 days
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%.
71 days
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%.
71 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of Treatment-Emergent Adverse Events (AEs)
Time Frame: 71 days
71 days
Local Infusion Tolerance
Time Frame: 71 days
71 days
Immunogenicity
Time Frame: 71 days
71 days
Measurement of C-reactive Protein
Time Frame: 71 days
71 days
Monitoring of Heart Function (ECG and Echocardiography)
Time Frame: 71 days
71 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mylan Pharmaceuticals Inc

Collaborators

Mylan GmbH

Investigators

  • Principal Investigator: Apinya Vutikullird, D.O., WCCT Global

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

October 29, 2015

First Submitted That Met QC Criteria

October 30, 2015

First Posted (Estimate)

November 3, 2015

Study Record Updates

Last Update Posted (Estimate)

November 3, 2015

Last Update Submitted That Met QC Criteria

October 30, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Myl-Her 1002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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