A Phase I, Randomised, Double-Blinded, Placebo Controlled, Safety and Pharmacokinetic Study of (Z)-Endoxifen in Healthy Female Volunteers
Atossa Genetics AUS Pty Ltd
24 participants
Jul 9, 2019
Interventional
Conditions
Summary
The purpose of this study is to test the safety and tolerability of two types of a potential breast cancer treatment called endoxifen. Who is it for? You may be eligible for this study if you are a healthy female aged 18-65. [***Please note participants who have cancer are not eligible for this study.***] Study details Participants in this study will be organised into two groups. One group will receive capsules to be taken by mouth, and the other group will receive tablets, to be taken by mouth. Within the capsule and tablet groups, participants will be randomised (by chance) to either the active drug or a placebo. Neither the participant nor investigators will know who gets the active or placebo drug. Initially, only a single capsule or tablet will be taken. After checking the results of this first day, participants may take their assigned tablet/capsule once a day for another 14 days. As part of this study, all participants will need to provide blood samples, urine samples, answer questionnaires and have a physical exam.
Eligibility
Inclusion Criteria19
- Healthy adult females, 18 to 65 years of age (inclusive) at the time of screening;
- Body Mass Index (BMI) within the range of 18 to 32 kg/m2 inclusive at screening;
- Absence of significant diseases which, at the physician's discretion, could have an impact on the volunteer's participation in the trial, according to protocol requirements, and study evaluations;
- Medically healthy without clinically significant abnormalities at the screening visit or Day -1,including:
- a. Electrocardiogram (ECG),
- b. Physical examination, vital signs including temperature, heart rate, respiratory rate and
- blood pressure;
- Screening laboratory tests that are deemed to be non-clinically significant by the investigator;
- Negative cotinine, drug and alcohol tests at screening and check in;
- Ability to understand the nature and objectives of the trial, including risks and adverse events;
- willingness to cooperate with the researcher and proceed according to all study requirements;
- Participants of child-bearing potential (a woman is considered of child-bearing potential unless she is permanently sterilized or post-menopausal for at least 12 months with no menses and no alternative medical cause) must agree to use one of the following appropriate contraceptive methods (hormonal contraception is not permitted)
- Complete abstinence from intercourse (with a male partner) for at least 14 days prior to dosing with study drug through the End-of-Study and at least 60 days after the conclusion of study drug administration, provided it is true abstinence consistent with the usual and ongoing lifestyle of the participant.
- b. A double-barrier method, i.e., condom and IUD;
- c. Sterilization (vasectomy) of male partner prior to commencement of the volunteer’s last normal menstrual
- Have no air travel commitments during the study and for four weeks following completion of the
- study treatment;
- Have suitable venous access for blood sampling;
- Willing and able to comply with the requirements of the study protocol.
Exclusion Criteria19
- Current or recent use of (within 3 months) of cigarettes or any other tobacco-containing product.
- Unexplained vaginal bleeding
- History or presence of:
- a. a clinically significant disorder including but not limited to: cardiovascular, pulmonary (with the exception of mild asthma – no prevention treatment within prior 6 months), hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past three months determined by the PI to be clinically relevant;
- b. deep vein thrombosis, pulmonary embolism or significant thrombosis in any other vein
- c. endometrial cancer, premalignant condition of the endometrium or a strong family history of endometrial cancer;
- d. arterial thrombotic disease such as stroke, coronary artery disease or peripheral vascular disease
- e. cataracts or retinal vein occlusion
- f. drug addiction, including alcohol, within 1 year;
- A family history (first degree relative) of venous thrombosis that was NOT due to a transient major risk factor, i.e., hip surgery, knee replacement.
- Current or recent (within 3 months) use of alcohol that exceeds 3 standard drinks per day
- Have a hypersensitivity or allergy to the investigational compound/compound class being used in this study or any ingredients of this medication;
- Treatment, within 3 months before the trial, with any drugs known to have a well-established toxic potential to major organs;
- Have participated in any other investigational study within 30 days of screening;
- 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 (including analgesics (paracetamol up to and including 2 g per day is permitted), herbal products or diet aids);
- Have received hormonal treatment (including use of hormonal contraceptives (oral contraceptive pills or implant)) within 3 months prior to commencement of study treatment;
- Pregnancy, labour or miscarriage within 12 weeks before commencement of study treatment;
- 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.
- Any conditions, that according to investigator's best judgment, prevent participation in the trial.
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Interventions
n=24healthy female subjects will be divided evenly into 2 groups, Group 1 (n = 12) receiving Z-endoxifen 4mg capsules or matching placebo and Group 2 (n = 12) receiving Z-endoxifen 4mg tablets or placebo. Subjects will all complete screening procedures from day -28 to day -2 prior to dosing. subjects will then check into the clinical facility on Day -1. Following confirmation of eligibility on Day 1 each subject will be receive 1 dose of study drug in the clinic. Subjects will remain in-house until Day 2, when they will check out of the facility. On Days 4, 6 and 15 subjects will return to the clinical facility to attend out-patient visits including safety tests and pharmacokinetics (PK). A Safety and PK Review Committee will review safety and PK data for all patients (Group 1 and Group 2) up to and including up to Day 6 samples. The Committee we determine if the study can safely move to the Multiple Administration Dosing (MAD) and whether Group 1 and Group 2 or Group 2 alone will be dosed in MAD. If the SAD PK results show equivalence for capsule and tablet, only the tablet group will be dosed in the MAD. On Day 26 subjects will attend an out-patient visit for safety and PK and will then be administered one dose of allocated study drug. The subject will continue to take 1 daily dose of study drug at home (or in clinic on out-patient days) for 14 days. Participants will complete a daily (paper) diary to record when study drug is dosed; adverse events and concomitant medications can also be recorded in the diary. Subjects will be reminded to return the study drug bottle, even if empty, at their clinic visit for the site to perform accountability and, together with the diary, to assess participant study drug compliance. Subjects will return to the clinic for safety assessments and PK on Day 32. Subjects will check in to the clinical facility on Day 38 and on Day 39 and undergo study assessments including blood draws for safety and PK before taking the final dose of study medication (Day 39). Subjects will remain at the clinical facility until Day 40 when they will be discharged. Subjects will then attend out-patient visits on Days 42, 44 and 46 for safety assessments. All study visits (out patient and in-house) will consist of PK and safety assessments.
Locations(1)
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ACTRN12619000961145