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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000569202
Ethics application status
Approved
Date submitted
21/03/2018
Date registered
13/04/2018
Date last updated
18/03/2019
Date data sharing statement initially provided
25/02/2019
Date results information initially provided
25/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase I, placebo controlled, dose escalation safety and
pharmacokinetic study of Topical Endoxifen in healthy male volunteers.
Scientific title
A phase I, placebo controlled, dose escalation safety and
pharmacokinetic study of Topical Endoxifen in healthy male volunteers.
Secondary ID [1] 294402 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gynecomastia 307134 0
Condition category
Condition code
Metabolic and Endocrine 306252 306252 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy male volunteers will be screened within 28 days prior to commencement of dosing.

Study consists of 3 cohorts, each cohort consisting of 8 participants with 6 participants receiving (Z)-Endoxifen topical and 2 participants receiving placebo topical. Three dose levels of topically applied (Z)-Endoxifen (2mg, 6mg, and 10 mg) will be investigated in the 3 cohorts. Participants will be admitted in the clinical facility on Day-1 and will receive the IMP in pre-sealed sachets for topical application on Day 1. They will be discharged on Day 2 and supplied with study drug sachets and asked to self-administer daily one sachet to each of the breast for 28 days.
Participants will return to the clinic weekly for PK sampling and assessment, as well as on Days 4, 31, 33 and 35.

Intervention code [1] 300693 0
Treatment: Drugs
Comparator / control treatment
Placebo topical, Containing: Transcutol P, Isopropanol, Crodamol GTCC, Mineral oil
Control group
Placebo

Outcomes
Primary outcome [1] 305257 0
To assess the safety and tolerability of (Z)-endoxifen when administered topically to the breast of healthy male volunteers and will include recording the incidence and severity of adverse events, vital sign parameters, physical examination findings, electrocardiogram parameters and clinical laboratory parameters (serum chemistry, hematology, coagulation, urinalysis).
Timepoint [1] 305257 0
The safety assessments mentioned above are composite primary outcome and will be done at each of the visits, weekly for a month and on days 4, 31, 33 and 35.
The blood pressure and pulse will be assessed by pulse oximetry while respiratory rate, physical examination will be assessed clinically. Temperature will be assessed by using a tympanic thermometer while an ECG will be recorded by an instrument which involves the placement of electrodes on the chest wall.
Blood will be collected for hematology, coagulation and clinical chemistry lab assessments while urine will be collected for urinalysis.
Secondary outcome [1] 344646 0
To assess the pharmacokinetics of multiple doses of (Z)-endoxifen when administered topically to the breast of healthy male volunteers.
Pharmacokinetic parameters which will be assessed include Cmax, Tmax, AUC0-24h, t1/2
Timepoint [1] 344646 0
Blood sampling for pharmacokinetic analysis will be performed at Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 29, Day 31, Day 33 and Day 35.
Secondary outcome [2] 344685 0
Assess the side effects associated with (Z)-endoxifen treatment using the modified FACT-ES questionnaire.
Timepoint [2] 344685 0
To be performed on Day 1, Day 7, Day 14, Day 21, Day 28 and Day 35.

Eligibility
Key inclusion criteria
1. Healthy adult males, 18 to 65 years of age (inclusive) at the time of screening;
2. Body Mass Index (BMI) within the range of 18 to 32 kg/m2 inclusive at screening;
3. Absence of significant diseases which, at the physician's discretion, could have an impact on the volunteer's participation in the trial,
4. Medically healthy without clinically significant abnormalities at the screening visit or Day -1,
5. Screening laboratory tests that are deemed to be non-clinically significant by the investigator;
6. Negative cotinine, drug and alcohol tests at screening and check in;
7. Ability to understand the nature and objectives of the trial
8. Participants with partners of child-bearing potential must agree to use condom and one
of the following contraceptive methods:
a. Complete abstinence from intercourse during the dosing with study drug through the End-of-Study and at least 60 days after the conclusion of study drug administration; OR
b. The female partner must be using effective contraception such as hormonal, IUD, a double-barrier method, or is sterilized; OR
c. Sterilization (vasectomy);
9. Have no air travel commitments during the study and for four weeks following completion of the study treatment;
10. Have suitable venous access for blood sampling;
11. Willing and able to comply with the requirements of the study protocol.
Minimum age
18 Years
Maximum age
65 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of a clinically significant disorder including but not limited to: cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric or neurological disease, including any acute
illness or surgery within the past three months determined by the PI to be clinically relevant;
2. History of drug addiction, including alcohol within 1 year;
3. Smokes or uses e-cigarettes;
4. Have a hypersensitivity or allergy to the investigational compound;
5. Treatment, within 3 months before the trial, with any drugs known to have a well-established toxic potential to major organs;
6. Have participated in any other investigational study within 30 days or 5 half-lives of the drug (whichever is longer) of screening;
7. Use of any medications or over the-counter products within 7 days or 5 half-lives (whichever is longer) prior to administration of study medication;
8. Have any history or evidence of procoagulant disorder, Deep Vein Thrombosis (DVT) or pulmonary embolism;
9. Donation of blood or plasma within 30 days prior to randomization, or loss of whole blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of study enrolment.
10. Any conditions, that according to investigator's best judgment, prevent participation in the trial.

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
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] 299035 0
Commercial sector/Industry
Name [1] 299035 0
Atossa Genetics, Inc.
Address [1] 299035 0
107 Spring St
Seattle, WA 98104
Country [1] 299035 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Atossa Genetics, Inc.
Address
107 Spring St
Seattle, WA 98104
Country
United States of America
Secondary sponsor category [1] 298267 0
None
Name [1] 298267 0
Address [1] 298267 0
Country [1] 298267 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299970 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 299970 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 299970 0
Australia
Date submitted for ethics approval [1] 299970 0
14/02/2018
Approval date [1] 299970 0
16/03/2018
Ethics approval number [1] 299970 0
2018-02-108

Summary
Brief summary
This study aims to assess the safety and tolerability of Topical Endoxifen when administered as a topical application to the breast of healthy male volunteers.
Who is it for?
You may be eligible to join this study if you are a healthy male volunteers aged between 18 and 65 years
Study details: This is a double-blind, placebo controlled, dose escalation trial investigating the safety and pharmacokinetics of Topical Endoxifen applied to the breasts of healthy male volunteers.
Three dose levels of Topical Endoxifen will be investigated in 3 cohorts. In each cohort, participants will be randomized to receive Topical Endoxifen or placebo in a blinded fashion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82130 0
Dr Ben Snyder
Address 82130 0
Nucleus Network Pty Ltd
The Burnet Tower, 5th Floor
89 Commercial Road
Melbourne
Victoria, 3004
Country 82130 0
Australia
Phone 82130 0
+613 9076 8960
Fax 82130 0
Email 82130 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 82131 0
Ms Janet R Rea
Address 82131 0
C/O Atossa Genetics Inc.
107 Spring St
Seattle, WA 98104
Country 82131 0
United States of America
Phone 82131 0
+1.206.799.7186
Fax 82131 0
Email 82131 0
janet.rea@atossagenetics.com
Contact person for scientific queries
Name 82132 0
Ms Janet R Rea
Address 82132 0
C/O Atossa Genetics Inc.
107 Spring St
Seattle, WA 98104
Country 82132 0
United States of America
Phone 82132 0
+1.206.799.7186
Fax 82132 0
Email 82132 0
janet.rea@atossagenetics.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The Individual Participant clinical trial data and metadata arising from this study are considered confidential, commercial trade secret information which is subject to subsequent product development and potential patent fillings relating to the formulation of the investigational product
What supporting documents are/will be available?
Study protocol
Clinical study report
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary