A Single Dose Trial to Evaluate the Pharmacokinetics of Testosterone and Anastrozole

Overview

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

Full Title of Study: “A Single Dose Trial to Evaluate the Pharmacokinetics of Testosterone and Anastrozole From Subcutaneous Testosterone and Anastrozole (T+Ai) in Premenopausal Women”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 17, 2018

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.

Interventions

  • Drug: testosterone anastrozole
    • subcutaneous testosterone and anastrozole

Arms, Groups and Cohorts

  • Experimental: testosterone anastrozole implant
    • testosterone 80mg Anastrozole 4 mg single as a subcutaneous pellet

Clinical Trial Outcome Measures

Primary Measures

  • testosterone Cmax
    • Time Frame: 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.
    • Peak Plasma Concentration
  • testosterone AUC
    • Time Frame: 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.
    • Area under the plasma concentration versus time curve
  • testosterone T1/2
    • Time Frame: 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.
    • plasma half-life
  • anastrozole Cmax
    • Time Frame: 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.
    • Peak Plasma Concentration
  • anastrozole AUC
    • Time Frame: 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.
    • Area under the plasma concentration versus time curve
  • anastrozole T1/2
    • Time Frame: 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.
    • plasma half-life

Secondary Measures

  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
    • Time Frame: The outcome measures will be reported weekly until study completion-3 months
    • To assess the safety and tolerability of T+Ai following a single dose of T+Ai by subcutaneous implantation. Biochemical and hematological will be evaluated and the number of participants with abnormal values or adverse events that are related to treatment will be recorded
  • dihydrotestosterone metabolism
    • Time Frame: 3 months
    • To description of the time course of dihydrotestosterone serum concentrations.
  • breast elasticity
    • Time Frame: Breast tissue elasticity will be measured by shear wave ultrasound at baseline and on Days 29, 57 and 85
    • Breast tissue elasticity will be measured by shear wave ultrasound at baseline and on Days 29, 57 and 85. A Supersonic Ultrasound will be carried out by four quadrant analysis of each breast with 6x3mm Q box analyses measured in kPa.

Participating in This Clinical Trial

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.

Gender Eligibility: Female

Minimum Age: 35 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Havah Therapeutics Pty Ltd
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Stephen N Birrell, Md PhD, Principal Investigator, Wellend Health

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