| Eligibility |
Inclusion Criteria:
1. Understand the study procedures in the informed consent form (ICF) and be willing and
able to comply with the protocol restrictions and requirements.
2. Males and Females older than 18 years.
3. Body mass index between 18.0 and 40.0 kg/m^2, inclusive.
4. Females must have non-functioning ovaries defined as postmenopausal and/or bilateral
salpingo - oophorectomy. All female subjects must have a negative pregnancy test at
screening and at check-in.
5. Males who are non-sterilized and sexually active with a female partner of childbearing
potential must agree to use highly effective contraception from admission and for 120
days after IMP dose.
6. Males must agree not to donate sperm from admission and for 120 days after
investigational medicinal product dose.
7. Non-smoker or light smoker, i.e. no more than 10 cigarettes or 10 mg equivalent use of
Nicotine per day by e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch,
nicotine gum, AND able or willing to refrain from smoking and tobacco use for 2 hours
prior to dose and 4 hours after IMP dose.
Additional inclusion criteria applicable to subjects with Normal Hepatic Function Only
8. In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory
evaluations. NOTE: Congenital nonhemolytic hyperbilirubinemia/Gilbert's syndrome based
on total and direct bilirubin is not acceptable.
9. Matched to subjects with severe hepatic impairment in gender, age (±10 years), weight
(±10 kg) and race.
Additional inclusion criteria applicable to subjects with Severe Hepatic Impairment
Only
10. Documented chronic stable severe liver disease according to Child Pugh (CP)
classification (CP score C) with diagnosis of hepatic impairment due to parenchymal
liver disease. This will exclude biliary liver cirrhosis or other causes of hepatic
impairment not related to parenchymal disorder.
- 'Documented' is defined by medical history and physical examination, and
confirmed by at least 1 of the following: hepatic ultrasound, computed axial
tomography scan, magnetic resonance imaging, and/or liver biopsy.
- 'Chronic' is defined as >6 months.
- 'Stable' is defined as no clinically significant change in disease status within
the last 6 weeks, as documented by the subject's recent medical history (eg, no
worsening of clinical signs of hepatic impairment, or no worsening of total
bilirubin or prothrombin time by more than 50%).
11. Subjects with severe hepatic impairment may have medical findings consistent with
their hepatic dysfunction as determined by medical history, physical examination,
12-lead ECG, vital sign measurements, and clinical laboratory evaluations at screening
and check-in (Day -1), as assessed by the Investigator, provided that the followings
are satisfied:
- Non-hepatic impairment-related, abnormal clinical laboratory evaluations must not
be clinically relevant, as judged by the Investigator and approved by the study
assigned medical monitor.
- Values outside the normal ranges for liver function tests are acceptable as
consistent with the subject's hepatic condition, provided they are stable for at
least 1 month prior to screening, as judged by the Investigator and approved by
the study assigned medical monitor.
- Subjects may enter with non-clinically significant Grade 1 anemia per CTCAE
version 5.0, i.e. with Hb > 10 mg/dL.
- Subjects must have a platelet count = 35 × 109 /L
12. Subjects with stable, mild, chronic concurrent diseases, such as degenerative joint
disease, hypertension or hyperlipidaemia, etc. may be included. Subjects with diabetes
mellitus may be included, provided the subjects have:
- Glycosylated hemoglobin A1c values = 9.5% at screening; eligibility in case of
outside values should be evaluated by the study assigned medical monitor on a
case-by-case basis.
- Blood glucose values = 240 mg/dL at screening and check-in (Day -1) while on
subjects' normal diabetes medication.
13. Currently on a stable medication regimen, defined as not starting new drug(s) or
changing drug dose(s) within 28 days of administration of study drug (Day 1).
Concomitant medications administered within 28 days prior to administration of study
drug (Day 1) must be approved by the Investigator and the study assigned medical
monitor.
Exclusion Criteria:
1. Presence of any condition or circumstance that prevents the subject from understanding
and signing the ICF.
2. Presence or history of any disorder that may prevent the successful completion of the
study.
3. History of significant hypersensitivity, intolerance, or allergy to food, or any
medical product or relevant excipient, unless approved by the Investigator.
4. History of allergy to Elacestrant or drugs in a similar pharmacology class (selective
ER modulator or SERD) or excipients used in the formulations of these drugs.
5. History of stomach or intestinal surgery or resection, or any significant
gastrointestinal disease (eg, Crohn's disease) that would potentially alter absorption
and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia
repair will be allowed). Cholecystectomy will be allowed at the discretion of the
Investigator.
6. Acute disease state (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to
check-in.
7. History of drug/chemical abuse within 1 year prior to check-in.
8. History of alcohol abuse within 3 months prior to screening and/or consume > 21 units
per week for males and > 14 units for females. One unit of alcohol equals 12 oz (360
mL) beer, 1 1/2 oz (45 mL) liquor, or 5 oz (150 mL) wine.
9. Positive drug screen at screening, or positive alcohol or drug screen at check-in.
10. Participation in a clinical study involving administration of an investigational drug
(new chemical entity) or device in the past 28 days or 5 half-lives (whichever is
longer) prior to dosing.
11. Received Elacestrant within 60 days prior to dosing.
12. Corrected value of the interval between the Q and T waves on the ECG tracing, using
Fridericia's formula, is > 450 ms (for healthy males) or > 470 ms (for healthy
females), is > 470 ms (for hepatic impairment males) or > 480 ms (for hepatic
impairment females); or has ECG findings deemed abnormal with clinical significance by
the Investigator at screening. ECGs will be collected in triplicate.
13. Use of any drugs or herbal remedies known to be strong or moderate inhibitors or
inducers of CYP3A enzymes for 28 days prior to dosing or 5 half-lives (whichever is
longer) and throughout the study.
14. Not willing to follow on-study diet requirements.
15. Ingestion of Seville orange- or grapefruit- containing foods or beverages within 28
days prior to check-in.
16. Receipt of blood products within 2 months prior to check-in.
17. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to
screening, or platelets from 6 weeks prior to screening.
18. Poor peripheral venous access.
19. Subjects who, in the opinion of the Investigator, should not participate in this
study.
Additional exclusion criteria applicable to Subjects with Normal Hepatic Function Only
20. Significant history or clinical manifestation of any metabolic, allergic,
dermatological, hepatic, renal, hematological, pulmonary, cardiovascular (including
any prior history of cardiomyopathy or cardiac failure), gastrointestinal,
neurological, or psychiatric disorder.
21. Unable to refrain from or anticipate the use of any non-prescription medications,
herbal remedies, or vitamin supplements within 14 days prior to dosing and throughout
the study.
NOTE: After check-in, acetaminophen (up to 2 g per 24 hours), and 1% hydrocortisone
cream may be administered at the discretion of the Investigator.
22. Unable to refrain from or anticipate the use of any prescription medications within 28
days prior to dosing or 5 half-lives (whichever is longer) and throughout the study,
unless approved by the Investigator and the study assigned medical monitor.
NOTE: slow-release medications / products considered to still be active prior to
check-in must be approved by the Investigator and the study assigned medical monitor.
23. Positive hepatitis B panel test and/or positive hepatitis C RNA test. Subjects whose
results are compatible with prior immunization may be included.
24. History of diabetes mellitus.
Additional exclusion criteria applicable to Subjects with Hepatic Impairment Only
25. Grade 3 and Grade 4 encephalopathy as determined by the CP score.
26. Portal systemic shunt.
27. Subject has shown evidence of hepatorenal syndrome or abnormal serum creatinine levels
(above upper limit for the local lab) and estimated glomerular filtration rate < 60
mL/min or abnormal sodium and potassium levels. The determination of the severity and
clinical relevance of the latter 2 abnormalities will be at the discretion of the
Investigator.
28. Treatment for gastrointestinal bleeding within the 3 months prior to check-in.
29. New medication or a change in dose for hepatic encephalopathy within the 3 months
prior to check-in, unless approved by the Investigator and the study assigned medical
monitor.
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