Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion

NCT ID: NCT02594761

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-02-28

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: DOUBLE

Study Groups

Treatment A

Hercules: 8 mg/kg i.v. infusion over 90 minutes

Group Type: EXPERIMENTAL

Hercules

Intervention Type: BIOLOGICAL

Powder Concentrate for Intravenous Infusion, 150 mg/vial

Treatment B

Herceptin EU: 8 mg/kg i.v. infusion over 90 minutes

Group Type: ACTIVE_COMPARATOR

Herceptin EU

Intervention Type: BIOLOGICAL

Powder for Concentrate for Solution for Infusion, 150 mg/vial

Treatment C

Herceptin US: 8 mg/kg i.v. infusion over 90 minutes

Group Type: ACTIVE_COMPARATOR

Herceptin US

Intervention Type: BIOLOGICAL

Intravenous Infusion, 440 mg/vial

Interventions

Hercules

Powder Concentrate for Intravenous Infusion, 150 mg/vial

Intervention Type: BIOLOGICAL

Herceptin EU

Powder for Concentrate for Solution for Infusion, 150 mg/vial

Intervention Type: BIOLOGICAL

Herceptin US

Intravenous Infusion, 440 mg/vial

Intervention Type: BIOLOGICAL

Other Intervention Names

Trastuzumab; Trastuzumab; Trastuzumab

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Mylan GmbH

INDUSTRY

Sponsor Role: collaborator

Mylan Pharmaceuticals Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Apinya Vutikullird, D.O.

Role: PRINCIPAL_INVESTIGATOR

WCCT Global

References

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.

Reference Type: DERIVED

PMID: 29926514 (View on PubMed)

Other Identifiers

Myl-Her 1002

Identifier Type: -

Identifier Source: org_study_id