| Eligibility |
PART I and II (postmenopausal women):
Inclusion Criteria:
- Healthy Caucasian female volunteers between 45 and 65 years (inclusive) at screening.
- Female volunteers must be either naturally (spontaneously) post-menopausal: Natural
(spontaneous) postmenopause is defined as being amenorrheic for at least 12 months
without an alternative medical cause with a screening follicle stimulating hormone
level >25.8 IU/L and 17ß-oestradiol serum levels less than 183 pmol/L (or the local
laboratory levels for post-menopause) OR must have had a bilateral
oophorectomy/bilateral salpingo-oophorectomy. Hysterectomised women can be included
only if they have had bilateral oophorectomy.
- Volunteers not taking hormone replacement therapy (HRT).
- Has a body weight between 50kg and 100kg inclusive and a body mass index (BMI) between
18.0-32.0 kg/m^2 inclusive.
- Satisfactory medical assessment with no clinically significant or relevant
abnormalities as determined by medical history, physical examination, vital signs,
12-lead electrocardiogram (ECG), and clinical laboratory evaluation (haematology,
biochemistry, coagulation and urinalysis) that is reasonably likely to interfere with
the volunteer's participation in or ability to complete the study as assessed by the
investigator.
- Ability to provide written, personally signed, and dated informed consent to
participate in the study, in accordance with the International Conference on
Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and
applicable regulations, before completing any study-related procedures.
- Ability to swallow multiple capsules at a time or (consecutively) one capsule at a
time.
- An understanding, ability, and willingness to fully comply with study procedures and
restrictions.
Exclusion Criteria:
- Post-menopausal women with less than 12 months amenorrhoea or women with amenorrhoea
due to other medical causes.
- Current or recurrent disease (e.g., cardiovascular, haematological, neurological,
endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that
could affect the action, absorption, or disposition of FOR-6219, or could affect
clinical assessments or clinical laboratory evaluations.
- Current or relevant history of physical or psychiatric illness that are not stable or
may require a change in treatment, use of prohibited therapies during the study or
make the subject unlikely to fully comply with the requirements of the study or
complete the study, or any condition that presents undue risk from the investigational
product or study procedures.
- Any other significant disease or disorder which, in the opinion of the Investigator,
may either put the subject at risk because of participation in the study may influence
the result of the study, or the subject's ability to participate in the study.
- The history or presence of any of the following cardiac conditions: known structural
cardiac abnormalities; family history of long QT syndrome; cardiac syncope or
recurrent, idiopathic syncope; exercise related clinically significant cardiac events.
- Any clinically significant abnormalities in rhythm, conduction or morphology of
resting ECG or clinically important abnormalities that may interfere with the
interpretation of corrected QT (QTc) interval changes.
- Has vital signs consistently outside of the following normal range. Supine blood
pressure (after at least 5 minutes of supine rest):
- Systolic blood pressure: 90 - 145 mmHg.
- Diastolic blood pressure: 40 - 95 mmHg.
- Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening.
- Evidence of pregnancy.
- Any other abnormal findings on vital signs, ECG, physical examination or laboratory
evaluation of blood and urine samples that the Investigator judges as likely to
interfere with the study or pose an additional risk in participating.
- Positive test results for alcohol or drugs of abuse.
- History or clinical evidence of substance and/or alcohol abuse within the two years
before screening.
- Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing
products in any form (e.g., gum, patch, electronic cigarettes) within three months
prior to the planned first day of dosing.
- Has used any medication that is either an inhibitor or inducer of CYP3A4 within 28
days or 10 half-lives (whichever is longer) prior to the planned first day of dosing.
Additionally, subjects must not have consumed other substances known to be potent
inhibitors or inducers of cytochrome P450 (CYP P450s) in the two weeks before the
planned first study drug administration.
- Has used any other prescription or over-the-counter medication (including herbal or
homeopathic preparations; excluding vitamin/mineral supplements and occasional
paracetamol) within 14 days or 10 half-lives (whichever is longer) prior to the
planned first day of dosing that the Investigator judges is likely to interfere with
the study or pose an additional risk in participating.
- Consumption of herbal remedies or dietary supplements containing St. John's Wort in
the 3 weeks before the planned Day 1 of the dosing period.
- Has received an investigational product or been treated with an investigational device
within 90 days prior to first drug administration and will not start any other
investigational product or device study within 90 days after last study drug
administration.
- Known or suspected intolerance or hypersensitivity to the investigational product, any
closely related compound, or any of the stated ingredients.
- History of significant allergic reaction (anaphylaxis, angioedema) to any product
(food, pharmaceutical, etc).
- Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first
day of dosing.
- Has a mental incapacity or language barriers precluding adequate understanding,
cooperation, and compliance with the study requirements.
- An inability to follow a standardised diet and meal schedule or inability to fast, as
required during the study.
- Prior screen failure (where the cause of the screen failure is not deemed to be
temporary), randomisation, participation, or enrolment in this study. Subjects who
initially failed due to temporary non-medically significant issues are eligible for
rescreening once the cause has resolved.
PART III (premenopausal women):
Inclusion Criteria:
- Healthy female volunteers between age 18-39 years (inclusive) at screening and not
planning pregnancy during the month following the study completion.
- The subject is premenopausal with a regular ovulatory menstrual cycle with an interval
of 26-31 days based on medical history during the past 3 months and as confirmed by
the control menstrual cycle prior to dosing.
- Volunteers not taking oral contraceptives.
- Has a body weight between 45kg and 90kg inclusive and a body mass index (BMI between
18.0-30.0 kg/m^2 inclusive).
- Satisfactory medical assessment with no clinically significant or relevant
abnormalities as determined by medical history, physical examination, vital signs,
12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry,
coagulation and urinalysis) that is reasonably likely to interfere with the
volunteer's participation in or ability to complete the study as assessed by the
investigator.
- Satisfactory medical assessment with no clinically significant or relevant
abnormalities as determined by gynaecological examination and transvaginal ultrasound
(TVUS), that would interfere with the assessment of the endometrial thickness or
endometrial biopsy.
- Ability to provide written, personally signed, and dated informed consent to
participate in the study, in accordance with the ICH Good Clinical Practice (GCP)
Guideline E6 (R2) (2016) and applicable regulations, before completing any
study-related procedures.
- Ability to swallow multiple capsules at a time or (consecutively) one capsule at a
time.
- An understanding, ability, and willingness to fully comply with study procedures and
restrictions.
- The subjects must agree to use the study-specific contraceptive methods from screening
up to 30 days after the follow-up visit.
Exclusion Criteria:
- Post-menopausal women, defined as with more than 12 months amenorrhoea.
- Current or recurrent disease (e.g., cardiovascular, haematological, neurological,
endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that
could affect the action, absorption, or disposition of FOR-6219, or could affect
clinical assessments or clinical laboratory evaluations.
- Current or recurrent gynaecological disease that could affect the clinical
assessments.
- Current or relevant history of physical or psychiatric illness that are not stable or
may require a change in treatment, use of prohibited therapies during the study or
make the subject unlikely to fully comply with the requirements of the study or
complete the study, or any condition that presents undue risk from the investigational
product or study procedures.
- Any other significant disease or disorder which, in the opinion of the Investigator,
may either put the subject at risk because of participation in the study may influence
the result of the study, or the subject's ability to participate in the study.
- The history or presence of any of the following cardiac conditions: known structural
cardiac abnormalities; family history of long QT syndrome; cardiac syncope or
recurrent, idiopathic syncope; exercise related clinically significant cardiac events.
- Any clinically significant abnormalities in rhythm, conduction or morphology of
resting ECG or clinically important abnormalities that may interfere with the
interpretation of QTc interval changes.
- Has vital signs consistently outside of the following normal range. Supine blood
pressure (after at least 5 minutes of supine rest):
- Systolic blood pressure: 90 - 140 mmHg.
- Diastolic blood pressure: 40 - 90 mmHg.
- Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening.
- Evidence of pregnancy
- Any other abnormal findings on vital signs, ECG, physical examination or laboratory
evaluation of blood and urine samples that the Investigator judges as likely to
interfere with the study or pose an additional risk in participating.
- Positive test results for alcohol or drugs of abuse.
- History or clinical evidence of substance and/or alcohol abuse within the two years
before screening.
- Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing
products in any form (e.g., gum, patch, electronic cigarettes) within three months
prior to the planned first day of dosing.
- Has used any medication that is either an inhibitor or inducer of CYP3A4 within 28
days or 10 half-lives (whichever is longer) prior to the planned first day of dosing.
Additionally, subjects must not have consumed other substances known to be potent
inhibitors or inducers of cytochrome P450 (CYP P450s) in the two weeks before the
planned first study drug administration.
- Has used any other prescription or over-the-counter medication (including herbal or
homeopathic preparations; excluding vitamin/mineral supplements, measures for pain
relief during biopsy (such as use of local anaesthetic and/or NSAIDs) and occasional
paracetamol) within 14 days or 10 half-lives (whichever is longer) prior to the
planned first day of dosing that the Investigator judges is likely to interfere with
the study or pose an additional risk in participating.
- Consumption of herbal remedies or dietary supplements containing St. John's Wort in
the 3 weeks before the planned Day 1 of the dosing period.
- Use of oral contraceptives, contraceptive intrauterine device, or any other hormonal
medication that may have an impact on the hormonal levels, assessment of endometrium
or follicle assessment during the menstrual cycle. The wash-out period for any
hormonal treatment is at least 3 menstrual cycles before dosing.
- Has received an investigational product or been treated with an investigational device
within 90 days prior to first drug administration and will not start any other
investigational product or device study within 90 days after last study drug
administration.
- Known or suspected intolerance or hypersensitivity to the investigational product, any
closely related compound, or any of the stated ingredients.
- History of significant allergic reaction (anaphylaxis, angioedema) to any product
(food, pharmaceutical, etc).
- Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first
day of dosing.
- Has a mental incapacity or language barriers precluding adequate understanding,
cooperation, and compliance with the study requirements.
- An inability to follow a standardised diet and meal schedule or inability to fast, as
required during the study.
- Prior screen failure (where the cause of the screen failure is not deemed to be
temporary), randomisation, participation, or enrolment in this study. Subjects who
initially failed due to temporary non-medically significant issues are eligible for
rescreening once the cause has resolved.
|
