HealthyPhase 1NCT02594761
Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion
A Phase 1 study testing Hercules, Herceptin EU and Herceptin US in people with Healthy, run by Mylan Pharmaceuticals Inc.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Hercules, Herceptin EU and Herceptin US
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- No sites listed yet
- Study dates
- Aug 2013to Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy adult subjects, age 18 to 55 years old
- able to understand procedures, agree to participate and willing to give informed consent
Who cannot join
- 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
About this study
Official title: 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.
Read the 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
- Being tested
- Hercules, Herceptin EU, Herceptin US
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HerculesBiological
Also called Trastuzumab
Powder Concentrate for Intravenous Infusion, 150 mg/vial
Herceptin EUBiological
Also called Trastuzumab
Powder for Concentrate for Solution for Infusion, 150 mg/vial
Herceptin USBiological
Also called Trastuzumab
Intravenous Infusion, 440 mg/vial
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | Hercules: 8 mg/kg i.v. infusion over 90 minutes Receives: Biological: Hercules |
| Treatment B | Active comparator | Herceptin EU: 8 mg/kg i.v. infusion over 90 minutes Receives: Biological: Herceptin EU |
| Treatment C | Active comparator | Herceptin US: 8 mg/kg i.v. infusion over 90 minutes Receives: Biological: Herceptin US |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Concentration (Cmax)
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%.
Measured: 71 days
Area Under the Plasma Concentration Versus Time Curve (AUC) - Time 0 to Last Blood Draw (AUC0-last)
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%.
Measured: 71 days
Area Under the Plasma Concentration Versus Time Curve (AUC) - Time 0 to Infinity AUC0-∞)
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%.
Measured: 71 days
Secondary outcomes (5)
Incidence of Treatment-Emergent Adverse Events (AEs)
Measured: 71 days
Local Infusion Tolerance
Measured: 71 days
Immunogenicity
Measured: 71 days
Measurement of C-reactive Protein
Measured: 71 days
Monitoring of Heart Function (ECG and Echocardiography)
Measured: 71 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study startAug 2013
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mylan Pharmaceuticals Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mylan GmbH
- Responsible party
- Sponsor
- Investigators
- Apinya Vutikullird, D.O., Principal investigator, WCCT Global
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02594761
- Sponsor's protocol ID
- Myl-Her 1002
- Status last verified
- Oct 2015
- First submitted
- 29 Oct 2015
- Last updated
- 3 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 29926514
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Study Comparing Hercules, EU-approved Herceptin® and US-Licensed Herceptin® Administered as a Single Intravenous Infusion to Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT02594761
- Acronym / sponsor ID
- Myl-Her 1002
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Mylan Pharmaceuticals IncIndustry (pharma, biotech, devices)
- Collaborators
- Mylan GmbH
- Study start
- Aug 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Biological: HerculesHercules: 8 mg/kg i.v. infusion over 90 minutes |
| Treatment B | Active comparator | Biological: Herceptin EUHerceptin EU: 8 mg/kg i.v. infusion over 90 minutes |
| Treatment C | Active comparator | Biological: Herceptin USHerceptin US: 8 mg/kg i.v. infusion over 90 minutes |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- healthy adult subjects, age 18 to 55 years old
- able to understand procedures, agree to participate and willing to give informed consent
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HerculesAlso: TrastuzumabPowder Concentrate for Intravenous Infusion, 150 mg/vial | Biological | Treatment A |
| Herceptin EUAlso: TrastuzumabPowder for Concentrate for Solution for Infusion, 150 mg/vial | Biological | Treatment B |
| Herceptin USAlso: TrastuzumabIntravenous Infusion, 440 mg/vial | Biological | Treatment C |
Primary outcome
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%.
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
- Derived from this study: PubMed 29926514Waller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Apinya Vutikullird, D.O. principal investigator
WCCT Global
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hercules, Herceptin EU and Herceptin US in people with Healthy, run by Mylan Pharmaceuticals Inc.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Plasma Concentration (Cmax) (time frame: 71 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02594761, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.