| Eligibility |
Inclusion Criteria:
- For participant with hepatic impairment: Participant must be 50 to 75 years of age,
inclusive, at the time of signing the informed consent.
-. For participant with normal hepatic function: Participant must be matched to
participant with hepatic impairment by age (±10 years; determined at the time of
signing the informed consent).
- For participant with hepatic impairment:
1. Participant must have medical history, physical examination, vital signs, ECGs,
and laboratory safety tests consistent with a diagnosis of hepatic impairment,
but is otherwise judged to be in good health as determined by the investigator at
screening and Day -1.
2. Participant must have a diagnosis of chronic (>6 months), stable (no acute
episodes of illness within the previous 2 months due to deterioration in hepatic
function) hepatic insufficiency with features of cirrhosis due to any aetiology
at screening and Day -1.
- For participant with normal hepatic function: Participants must be medically healthy
with no clinically significant medical history, physical examination, laboratory
profiles (including serum amylase and lipase, haematology, and thyroid function),
vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1
- For participant with hepatic impairment: Body weight within 50 to 100 kg and BMI
within the range 19.0 to 35.0 kg/m2 (inclusive) as measured at screening.
- For participant with normal hepatic function: Participant must be matched to
participant with hepatic impairment by weight in kg (±20%; data obtained at
screening).
- Female, post-menopausal. (a) Women will be considered post-menopausal if they have
been amenorrhoeic for 12 months prior to the planned date of study intervention
without an alternative medical or surgical cause, confirmed by an FSH result of = 30
IU/L obtained at screening.
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
- Must agree to not use warfarin or phenytoin (and other coumarin-derived vitamin K
antagonist anticoagulants) from screening, throughout the study, and for 2 weeks after
the dose of study drug
Exclusion Criteria:
- History of or ongoing, clinically significant, in the opinion of the investigator,
visual disturbances including, but not limited to, visual hallucinations, migraine
with visual symptoms, blurred vision, and frequent floaters/flashes associated with
other symptoms such as dizziness at screening or Day -1
- History or presence of clinically significant or unstable medical or psychiatric
condition or disease in the opinion of the investigator at screening or Day -1
- Participant is mentally or legally incapacitated or has significant emotional problems
at the time of the screening or Day -1 visit or expected during the conduct of the
study
- History of any illness that, in the opinion of the investigator, might confound the
results of the study or poses an additional risk to the participant by their
participation in the study noted at screening or Day -1
- Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral
infections (including upper respiratory tract infections, but excluding localized
cutaneous fungal infections), in the opinion of the investigator at screening or Day
-1
- History of any major surgical procedure within 30 days prior to the dose of study drug
- Any clinically significant condition that may affect camizestrant absorption in the
opinion of the investigator, including gastric restrictions and bariatric surgery (eg,
gastric bypass), noted at screening or Day -1
- Signs or confirmation of COVID-19 infection at screening or Day -1
- Unable to refrain from or anticipates the use of:
1. Any drugs known to prolong QT interval or drugs associated with a known risk of
Torsades de pointes within 4 weeks or 5 PK half-lives (whichever is longer) prior
to the dose of study drug and throughout the study.
2. Use of any prescribed or non-prescribed medication
3. Any drug known to be moderate or strong inhibitors or inducers of CYP3A and/or
P-gp, including St. John's Wort, within 14 and 28 days, respectively, prior to
the dose of study drug and throughout the study unless they are deemed acceptable
following consultation with the sponsor medical monitor and the investigator.
4. Human immunodeficiency virus protease inhibitor, anticoagulant within 14 days
prior to the dose of study drug and throughout the study.
5. Acetaminophen and ethacrynic acid within 24 hours prior to the dose of study drug
and throughout the study.
- Dosed in another clinical trial within 28 days or 5 half-lives (if known), whichever
is longer, prior to the dose of study drug
- Previous enrolment in the present study.
- Any clinically significant abnormalities at screening or Day -1 on 12-lead ECG as
judged by the investigator
- Known history of hypersensitivity to active or inactive excipients of camizestrant or
drugs with a similar chemical structure or class to camizestrant noted at screening or
Day -1
- Donation of blood > 500 mL or significant blood loss within 56 days prior to the dose
of study drug
- Plasma donation within 28 days prior to the dose of study drug.
- Is working at or has an immediate family member (spouse or children) who works at the
investigational site or is a sponsor staff directly involved with this study."
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)."
- Judgment by the investigator that the participant should not participate in the study
if the participant is unlikely to comply with study procedures, restrictions, and
requirements.
- Participants with hepatic impairment are excluded from the study if any of the
following criteria apply:
- History or presence of drug abuse within the past 2 years prior to screening.
- Positive results for the alcohol test and/or urine drug screen at screening or
Day -1
- Positive results at screening for hepatitis B surface antigen or HCV
- Known history of HIV
- Participant has evidence of hepatorenal syndrome or creatinine clearance < 60
mL/minute
- History of unstable diabetes mellitus
- Presence of transjugular intrahepatic portosystemic shunt."
- Participants with normal hepatic function are excluded from the study if any of the
following criteria apply:
- History or presence of clinically significant thyroid disease
- History or presence of alcoholism and/or drug abuse within the past 2 years prior
to screening.
- Positive results for the alcohol test and/or urine drug screen at screening or
Day -1
- Known history of HIV, positive results at screening for hepatitis B surface
antigen or HCV.
- Participant has creatinine clearance <80 mL/minute
- Supine blood pressure < 90/40 mmHg or > 150/95 mmHg at screening or Day -1.
- Supine pulse rate < 50 bpm or > 99 bpm at screening or Day -1.
- Haemoglobin level below the lower limit of normal at screening or Day -1
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