Clinical trial NCT03314298: A Single Dose Trial to Evaluate the Pharmacokinetics of Testosterone and Anastrozole
Official title: A Single Dose Trial to Evaluate the Pharmacokinetics of Testosterone and Anastrozole From Subcutaneous Testosterone and Anastrozole (T+Ai) in Premenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mammographic Density
Lead sponsor: Havah Therapeutics Pty Ltd
Sponsor class: INDUSTRY
First posted: 2017-10-19
Enrollment: 11
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open labelled pharmacokinetic study
Primary purpose: PREVENTION

Brief summary: A single dose trial to evaluate the pharmacokinetics of testosterone and anastrozole from subcutaneous testosterone and anastrozole (T+Ai) in premenopausal women

Detailed description: The trial is of open label single centre design. The serum concentrations of testosterone and plasma concentrations of anastrozole will be measured in 12 premenopausal women. Participants will be stratified in a 50:50 manner in two BMI (Body Mass Index) groups, \<25 and 25 kg/m2, respectively. There will be a lead group of two participants in whom the serum/plasma concentrations will be examined after the first four weeks, to determine whether the sampling schedule adequately describes the serum/plasma concentration-time profiles or should be adjusted.

Eligibility criteria: Inclusion Criteria:

1. Agree to and be capable of understanding and signing an Informed Consent Form.
2. Patients seeking treatment with Investigational Product for the reduction in high mammographic breast density (MBD).
3. Pre-menopausal levels of Follicular stimulating hormone/Leutinizing hormone/estradiol(follicle stimulating hormone/luteinizing hormone/oestrogen) according to the definition of "pre-menopausal range" for the laboratory involved.
4. Volpara Density volumetric breast density of ≥15.5% (combined average both breasts)
5. Age between 35-55 years inclusive.
6. Body weight between 50-90 kg inclusive.
7. BMI between 20-30 kg/m2 inclusive.
8. Good venous access for venepuncture.
9. In good general health without clinically significant cardiac, respiratory, or psychiatric disease.
10. Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilisation), no more than seven days before the first dose of Investigational Product.
11. For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception (Mirena (TM) allowed) during and for at least six months after completion of treatment with Investigational Product; OR, a fertile male partner willing and able to use effective non-hormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilisation) during and for at least six months after completed dosing Investigational Product.

Exclusion Criteria:

1. Presence of breast cancer.
2. Previous or concomitant other malignancy (non-breast, other than skin) within the previous five years.
3. Diabetes mellitus or glucose intolerance defined as a fasting glucose of ≥ 6 mmol/L.
4. History of coronary artery disease.
5. Risk of transmitting Human Immunodeficiency Virus or viral hepatitis via infected blood.
6. Existing testosterone, oestrogen and/or anastrozole treatment.
7. Concomitant medication which induces or inhibits CYP3A4 (Listed in Appendix A).
8. Current warfarin usage.
9. Prolonged systemic corticosteroid treatment, inhalation and topical steroids allowed.
10. Known hypersensitivity to any component of Investigational Product.
11. Systemic reproductive hormone replacement therapy.
12. Systemic hormonal contraception.
13. Participation in another clinical trial of an Investigational Product within 30 days of entry into the present trial or within 4-5 half-lives of the Investigational Product, whichever is the longer.
14. Use of any product containing ginseng within 30 days of screening.
15. Pregnant or lactating women.
16. Unable to comply with trial requirements.

Primary outcomes:
measure: testosterone Cmax
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
measure: testosterone AUC
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
measure: testosterone T1/2
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
measure: anastrozole Cmax
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
measure: anastrozole AUC
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
measure: anastrozole T1/2
timeFrame: Day 1, blood samples will be taken pre-dose and at 1, 2, 4, 8 and 12 hours and 9 am in the morning on Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71 and 85.
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: The outcome measures will be reported weekly until study completion-3 months
measure: dihydrotestosterone metabolism
timeFrame: 3 months
measure: breast elasticity
timeFrame: Breast tissue elasticity will be measured by shear wave ultrasound at baseline and on Days 29, 57 and 85
Other outcomes:
Locations:
city: Toorak Gardens
country: Australia
facility: Wellend Health
state: South Australia
Study officials:
affiliation: Wellend Health
name: Stephen N Birrell, Md PhD
role: PRINCIPAL_INVESTIGATOR
References: