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Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion

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ClinicalTrials.gov Identifier: NCT02594761
Recruitment Status : Completed
First Posted : November 3, 2015
Last Update Posted : November 3, 2015
Sponsor:
Collaborator:
Mylan GmbH
Information provided by (Responsible Party):
Mylan Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 29, 2015
First Posted Date  ICMJE November 3, 2015
Last Update Posted Date November 3, 2015
Study Start Date  ICMJE August 2013
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
  • 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%.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
  • Incidence of Treatment-Emergent Adverse Events (AEs) [ Time Frame: 71 days ]
  • Local Infusion Tolerance [ Time Frame: 71 days ]
  • Immunogenicity [ Time Frame: 71 days ]
  • Measurement of C-reactive Protein [ Time Frame: 71 days ]
  • Monitoring of Heart Function (ECG and Echocardiography) [ Time Frame: 71 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion
Official Title  ICMJE Pharmacokinetic Study Comparing Hercules, EU-approved Herceptin® and US-Licensed Herceptin® Administered as a Single Intravenous Infusion to Healthy Male Volunteers
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Condition  ICMJE Healthy
Intervention  ICMJE
  • Biological: Hercules
    Powder Concentrate for Intravenous Infusion, 150 mg/vial
    Other Name: Trastuzumab
  • Biological: Herceptin EU
    Powder for Concentrate for Solution for Infusion, 150 mg/vial
    Other Name: Trastuzumab
  • Biological: Herceptin US
    Intravenous Infusion, 440 mg/vial
    Other Name: Trastuzumab
Study Arms  ICMJE
  • Experimental: Treatment A
    Hercules: 8 mg/kg i.v. infusion over 90 minutes
    Intervention: Biological: Hercules
  • Active Comparator: Treatment B
    Herceptin EU: 8 mg/kg i.v. infusion over 90 minutes
    Intervention: Biological: Herceptin EU
  • Active Comparator: Treatment C
    Herceptin US: 8 mg/kg i.v. infusion over 90 minutes
    Intervention: Biological: Herceptin US
Publications * Waller CF, Vutikullird A, Lawrence TE, Shaw A, Liu MS, Baczkowski M, Sharma R, Barve A, Goyal P, Donnelly C, Sengupta N, Pennella EJ. A pharmacokinetics phase 1 bioequivalence study of the trastuzumab biosimilar MYL-1401O vs. EU-trastuzumab and US-trastuzumab. Br J Clin Pharmacol. 2018 Oct;84(10):2336-2343. doi: 10.1111/bcp.13689. Epub 2018 Jul 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 30, 2015)
132
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02594761
Other Study ID Numbers  ICMJE Myl-Her 1002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mylan Pharmaceuticals
Study Sponsor  ICMJE Mylan Pharmaceuticals
Collaborators  ICMJE Mylan GmbH
Investigators  ICMJE
Principal Investigator: Apinya Vutikullird, D.O. WCCT Global
PRS Account Mylan Pharmaceuticals
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP