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Trial registered on ANZCTR


Registration number
ACTRN12616000084482
Ethics application status
Approved
Date submitted
22/01/2016
Date registered
27/01/2016
Date last updated
17/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A study comparing the blood levels of two trastuzumab formulations given as a single dose in healthy adult males.
Scientific title
A randomized, double-blind, parallel, single dose comparative pharmacokinetic study of two humanized monoclonal antibodies targeting HER2 receptors (i.e. trastuzumab) in healthy adult male subjects
Secondary ID [1] 288395 0
none
Universal Trial Number (UTN)
Trial acronym
TZ-01-003
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 297401 0
Condition category
Condition code
Cancer 297590 297590 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
trastuzumab 150 mg single dose by intravenous infusion by a healthcare provider
Intervention code [1] 293701 0
Treatment: Drugs
Comparator / control treatment
Herceptin 150 mg single dose by intravenous infusion.
Control group
Active

Outcomes
Primary outcome [1] 297133 0
Area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration, estimated using linear up/log down trapezoidal summation, assessed in the serum sample.
Timepoint [1] 297133 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Primary outcome [2] 297134 0
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinity, calculated by linear up/log down trapezoidal summation and extrapolated to infinity, assessed from serum sample.
Timepoint [2] 297134 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Primary outcome [3] 297135 0
Maximum observed concentration over the entire sampling interval, assessed in the serum sample.
Timepoint [3] 297135 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Secondary outcome [1] 320119 0
Time to maximum observed concentration, assessed in the serum sample.
Timepoint [1] 320119 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Secondary outcome [2] 320120 0
Apparent terminal rate constant, assessed in serum sample.
Timepoint [2] 320120 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Secondary outcome [3] 320121 0
Terminal half-life, assessed in serum sample.
Timepoint [3] 320121 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.
Secondary outcome [4] 320122 0
Incidence of adverse events/ serious adverse events. The most
common adverse reactions in patients receiving trastuzumab in the adjuvant and metastatic breast cancer setting are:
- Fever
- Nausea, vomiting
- Infusion reactions
- Diarrhoea
- Infections
- Increased cough, dyspnoea
- Headache, fatigue, myalgia, rash, neutropenia/anaemia. Adverse events are reported by the investigator and recorded on the case report form, as are out of range laboratory test results.
Timepoint [4] 320122 0
All AEs/SAEs are reported from the start of dose administration until the end-of-study visit.
Secondary outcome [5] 320123 0
Incidence of antibodies against trastuzumab in the serum sample.
Timepoint [5] 320123 0
Serum samples taken at the end of infusion and at 0.5, 1, 6, 24, 48, 72, 96 and 168 hours, and at Days 15, 22, 29, 36, 50, 64 and 78.

Eligibility
Key inclusion criteria
- Signed and dated written informed consent prior to any study-specific procedures, ability to understand and willingness to comply with the study procedures, restrictions
and requirements as judged and confirmed by the Investigator
- Healthy adult male subjects, 18 to 55 years (both inclusive) of age at the time of signing informed consent.
- Having body mass index (BMI) between 18-30 kg/m2 and body weight between 50 – 100 kg (all inclusive).
- Subjects with no clinically relevant abnormalities detected during baseline history, physical examination and vital signs (blood pressure, pulse rate, body temperature, including respiratory rate).
- Subjects who are considered healthy as determined by clinically acceptable findings of hemogram, biochemistry, coagulation tests, negative serology (HIV, Hepatitis B and
Hepatitis C), urinalysis, 12 lead ECG and echocardiogram.
- Subjects having normal thyroid function (subjects on thyroid supplementation therapy are not allowed for study participation).
- Subjects must refrain from donating sperm or fathering a child during the study and until 6 months after the last study drug (DRL_TZ and EU-approved Herceptin Registered Trademark) administration by agreeing to use (with their female partner) 02 acceptable contraceptives such as intrauterine device (IUD); oral, transdermal, injected, or implanted contraceptive; condoms; occlusive cap (diaphragm or cervical vault caps); spermicidal foam/gel/cream, etc.
- Non-smokers or ex-smokers who have not smoked within the previous 6 months from the screening visit and who agree to continue to abstain from smoking and using tobacco products throughout the course of the study.
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known history of hypersensitivity or allergic reactions to trastuzumab or any of its excipients.
- History of cardiovascular, hepatic, ophthalmic, pulmonary, neurological, metabolic, haematological, gastrointestinal, endocrine, immunological, psychiatric or any other disease which in the opinion of the investigator would make the subject inappropriate for study participation.
- Abnormal and clinically relevant (in the opinion of the Investigator) ECG, history of angina, exertional dyspnea, orthopnoea, congestive heart failure or myocardial infarction.
- History of any cancer, including carcinoma in situ.
- Use of prescription or non-prescription drugs, including herbal and dietary supplements (including St. John’s Wort, but with the exception of paracetamol at doses up to 4 grams
per day, or vitamins) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise subject safety.
- Use of haematopoetic growth factors, monoclonal antibodies or immunoglobulins within last 6 months or 5 half-lives, whichever is longer.
- Major surgery or major trauma within past one year of screening or anticipated need for any surgery during the study duration.
- Difficulty in blood sampling or difficulty in accessibility of veins.
- Prior history of or current alcohol abuse or excessive intake of alcohol (defined as alcohol intake of > 3 standard drinks/day) and/or a positive test result in breath alcohol test
done before check-in.
- Positive test result for cotinine (>500 ng/ml) or drugs of abuse at screening or on admission to the study centre.
- Blood donation within 90 days prior to commencement of
study and during the study.
- Participation in an investigational antibody based study within 120 days and any other investigational study within 90 days prior to dosing.
- Participation in a study with trastuzumab or HER 2 targeted antibody or any prior exposure to these drugs.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 292748 0
Commercial sector/Industry
Name [1] 292748 0
Dr Reddy's Laboratories Limited
Address [1] 292748 0
Bachupally, Qutublapur Mandal, R.R Dist, Hyderabad 500090
Country [1] 292748 0
India
Primary sponsor type
Commercial sector/Industry
Name
Dr Reddy's laboratories (Australia) Pty Ltd
Address
Level 9, 492 St Kilda Road, Melbourne, Victoria 3004
Country
Australia
Secondary sponsor category [1] 291478 0
None
Name [1] 291478 0
Address [1] 291478 0
Country [1] 291478 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294235 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 294235 0
55 Commercial Rd, Prahran, VIC, 3181
Ethics committee country [1] 294235 0
Australia
Date submitted for ethics approval [1] 294235 0
26/11/2015
Approval date [1] 294235 0
10/12/2015
Ethics approval number [1] 294235 0
542/15

Summary
Brief summary
The primary purpose of this study is to compare two formulations of trastuzumab to determine whether a new formulation produces similar blood levels to the current product. Who is it for? You may be eligible to participate in this study if you are a healthy male, aged 18 to 55, with a BMI of 18-30 and body weight of 50-100kg. Study details Participants enrolled in this trial will be randomly allocated (by chance) to receive a single dose of either the existing formulation of trastuzumab (known as Herceptin), or the new formulation of trastuzumab. After the single dose has been administered, blood samples will be taken [at the end of infusion and at 0.5, 1 6, 24, 48, 72, 96 and 168 hours and at Days 15, 22, 29, 36, 50, 64 and 78], to check the concentration of the drug in the blood over time. Researchers will also monitor participants for side effects e.g. by physical examination etc, until Day 78. It is hoped that the findings of this study will provide information on whether the new formulation of trastuzumab is equivalent to the existing formulation in the manner in which it is moved through and absorbed by the body.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62994 0
Dr Jason Lickliter
Address 62994 0
Centre for Clinical studies
Level 5, Burnet Tower
AMREP Precinct
89 Commercial Road
Melbourne, 3004 VIC
Country 62994 0
Australia
Phone 62994 0
+61 3 9076 8960
Fax 62994 0
Email 62994 0
j.licliter@nucleusnetwork.com.au
Contact person for public queries
Name 62995 0
Dr Jason Lickliter
Address 62995 0
Centre for Clinical studies
Level 5, Burnet Tower
AMREP Precinct
89 Commercial Road
Melbourne, 3004 VIC
Country 62995 0
Australia
Phone 62995 0
+61 3 9076 8960
Fax 62995 0
Email 62995 0
j.licliter@nucleusnetwork.com.au
Contact person for scientific queries
Name 62996 0
Dr Jason Lickliter
Address 62996 0
Centre for Clinical studies
Level 5, Burnet Tower
AMREP Precinct
89 Commercial Road
Melbourne, 3004 VIC
Country 62996 0
Australia
Phone 62996 0
+61 3 9076 8960
Fax 62996 0
Email 62996 0
j.licliter@nucleusnetwork.com.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary