None listed
Conditions
Brief summary
This study aims to evaluate the safety and pharmacokinetic study of (Z)-Endoxifen escalated doses in healthy female volunteers. Who is it for? You may be eligible to join this study if you are a healthy female aged between 18 and 65 years of age. Study details: This is a placebo controlled, dose escalation study. The study will be conducted in two parts in a total of 6 cohorts. In Part A, each participant will receive twenty eight doses of (Z)-Endoxifen or placebo as a topical application to the breast. In Part B, participants will receive fifteen doses of (Z)-Endoxifen or placebo capsules orally. Three different dose levels of (Z)-Endoxifen will be investigated in each part of the study. In both parts, sequential cohorts will be exposed to increasing doses of (Z)-Endoxifen. By substituting Tamoxifen treatment with Endoxifen the study will help in providing an improved approach towards treating patients with breast cancer because it bypasses the CYP2D6 enzyme that is required for metabolic activation of Tamoxifen.
Interventions
There are two parts for this study. Healthy female volunteers for both these parts will be screened within 28 days prior to commencement of dosing.
Part A (Topical Application) 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
There are two parts for this study. Healthy female volunteers for both these parts will be screened within 28 days prior to commencement of dosing. Part A (Topical Application) 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. Part B (Oral Administration) consists of 3 cohorts, each cohort consisting of 8 participants with 6 participants receiving (Z)-Endoxifen capsule and 2 participants receiving placebo capsule. Three dose levels of orally administered (Z)-Endoxifen (1 mg, 2 mg, and 4 mg) will be investigated in 3 cohorts. Two participants (Sentinels) will be dosed 24 hours prior to the remaining participants. One sentinel will be dosed with (Z)-Endoxifen and the other with placebo. The remaining six participants will only be dosed if no safety concerns are identified in the sentinel participants. There will be no sentinels in the other two cohorts. Participants will be admitted in the clinical facility on Day-1 and will receive the oral capsules on Day 1. PK blood draws will be performed, prior to discharge on Day 2. Additional PK sampling and safety assessments will be performed on Days 4 and 6. On Day 8 participants will commence daily administration of (Z)-Endoxifen capsules or placebo capsules for 14 consecutive days (Days 8-21) and will be supplied with study drug capsules and asked to self administer daily. Participants will visit the clinical facility on Days 11, 14 and 17, prior to dose administration, for PK blood draws and safety assessments. On Day 21, participants will return to the clinical facility prior to dose administration to allow for the collection of PK blood draws and safety assessments, and discharged the following day. Participants will return for PK blood draws and safety assessments on study Days 24, 26, and 28.
Sponsors
Atossa Genetics, Inc.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Body Mass Index (BMI) within the range of 18 to 30 kg/m2 inclusive at screening; 2. Absence of significant diseases based on physician's discretion; 3. 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; 4. Screening laboratory tests that are deemed to be non-clinically significant by the investigator; 5. Negative cotinine, drug and alcohol tests at screening and check in; 6. 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; 7. 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: a. 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 b. If unplanned intercourse a double-barrier method, i.e., condom and diaphragm or IUD must be used (hormonal contraception is not permitted); c. Sterilization (vasectomy) of male partner prior to commencement of the volunteer’s last normal menstrual period prior to Screening, and the male partner is the sole partner for that female volunteer; d. If the volunteer has a same sex partner, they must be willing to abstain from penile-vaginal intercourse. If penile-vaginal intercourse is to occur, the volunteer must be willing to comply with the contraceptive requirements above. 8. Have no air travel commitments during the study and for four weeks following completion of the study treatment; 9. Have suitable venous access for blood sampling;
Exclusion criteria
1. History or presence of a clinically significant disorder including but not limited to: cardiovascular, pulmonary, hepatic, renal, hematological, 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; 2. History of drug addiction, including alcohol within 1 year; 3. Have a hypersensitivity or allergy to the investigational compound/compound class being used in this study or any ingredients of this medication; 4. Treatment, within 3 months before the trial, with any drugs known to have a well established toxic potential to major organs; 5. Have participated in any other investigational study within 30 days of screening; 6. 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); 7. Have received hormonal treatment (including use of hormonal contraceptives (oral contraceptive pills or implant)) within 3 months prior to commencement of study treatment; 8. Pregnancy, labour or miscarriage within 12 weeks before commencement of study treatment; 9. Have recent history or evidence of procoagulant disorder, Deep Vein Thrombosis (DVT) or pulmonary embolism; 10. 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 enrollment. 11. Any conditions, that according to investigator's best judgment, prevent participation in the trial.
Outcome results
None listed