Effect of moderate or severe liver impairment on the pharmacokinetics, safety and tolerability of camizestrant in post‑menopausal women

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What is this study about?

The study looks at women who have stopped having periods naturally (post‑menopausal) and who have moderate or severe hepatic impairment, which means the liver does not work as well as it should. The medication being tested is an oral tablet called Camizestrant (AZD9833), taken as a single dose of 75 mg.

The aim of the research is to compare how the body handles the drug (pharmacokinetics) in participants with liver problems versus those with normal liver function. Participants will receive one tablet, then stay for a short period of observation during which blood samples are taken and basic health checks such as heart rhythm, blood pressure, and lab tests are performed to see if any side effects occur.

The study follows each participant for a limited time after the dose to record any safety concerns and to determine whether the medication is tolerated well enough to consider further testing.

1 baseline assessments

on the first visit after enrollment, a series of baseline checks are performed. these include a review of medical history, a physical examination, measurement of vital signs such as blood pressure and heart rate, an electrocardiogram (ecg) to record heart activity, and laboratory tests of blood and urine to evaluate liver function and overall health. the purpose is to document the condition before receiving the study drug.

2 receive study medication

after the baseline checks, the participant takes a single oral dose of camizestrant. the tablet is film‑coated, contains 75 mg of the active substance, and is swallowed with water under the supervision of study staff. this is the only dose taken during the trial.

3 blood sampling for drug level measurement

following the dose, blood samples are collected at several time points to determine how the drug is absorbed, distributed, metabolized, and eliminated (the study of pharmacokinetics). samples are usually taken within the first few hours and later in the day to capture the peak concentration and how quickly the drug level declines.

4 immediate safety monitoring

while the participant remains at the clinic, staff monitor for any immediate reactions. vital signs are checked regularly, the ecg may be repeated, and the participant is asked about any new symptoms or discomfort, known as adverse events (aes).

5 follow‑up visits

after leaving the clinic, the participant returns for scheduled follow‑up visits, typically on the next day and several days later (for example, day 2, day 7, and day 14). during these visits, vital signs, laboratory tests, and the ecg are repeated, and the participant is asked again about any adverse events. these visits help assess the safety and tolerability of the single dose.

6 final assessment and study completion

at the last study visit, a final set of safety checks is performed, including vital signs, laboratory tests, and an ecg. the participant receives a summary of the study procedures completed and is discharged from the trial. no further doses of camizestrant are taken.

Who Can Join the Study?

Be a woman who is post‑menopausal, meaning you have not had a period for at least 12 months and there is no other medical or surgical reason for it; this will be confirmed with a blood test showing FSH (follicle‑stimulating hormone) level of 30 IU/L or higher.
Be between 50 and 75 years old (inclusive) at the time you sign the consent form if you have liver problems.
If you have normal liver function, your age must be within ±10 years of a participant with liver problems.
If you have liver problems, you must have a medical history, physical exam, vital signs, an ECG (heart rhythm test), and lab tests that show a diagnosis of liver impairment, and you must otherwise be judged to be in good health.
If you have liver problems, you must have chronic (more than 6 months) and stable liver insufficiency with signs of cirrhosis (scarring of the liver) from any cause, and you must not have had any sudden worsening of liver function in the past 2 months.
If you have normal liver function, you must be medically healthy with no significant medical history, normal physical exam, normal vital signs, and normal lab results—including tests for serum amylase and lipase (pancreas enzymes), blood counts, and thyroid function—and a normal 12‑lead ECG.
If you have liver problems, your body weight must be between 50 kg and 100 kg, and your BMI (body‑mass index) must be between 19.0 and 35.0 kg/m².
If you have normal liver function, your weight must be within ±20 % of the weight of the matched participant with liver problems.
You must be able to understand the study and sign an informed consent form, agreeing to follow all study rules.
You must agree not to take warfarin or phenytoin (or any similar blood‑thinning medicines that affect vitamin K) from the time you are screened, during the study, and for two weeks after receiving the study drug.

Who Cannot Join the Study?

Having a history of or current serious eye problems such as visual hallucinations, migraines with visual symptoms, blurry vision, or frequent flashes/floaters with dizziness at the time of screening.
Having a serious or unstable medical or mental health condition that the doctor thinks could affect the study, noted at screening.
Being mentally or legally unable to give consent, or having strong emotional problems at screening or during the study.
Having any illness that the doctor believes could confuse the study results or add extra risk for the participant.
Having an ongoing systemic bacterial, fungal, or viral infection (including common colds or flu), except for a simple skin fungal infection.
Having had a major surgery within 30 days before receiving the study drug.
Having any condition that might change how the study drug is absorbed, such as stomach surgery (e.g., gastric bypass) or severe stomach restrictions.
Showing signs of COVID‑19 infection or having a confirmed COVID‑19 test at screening.
Being unable to avoid certain medicines, including:
- Drugs that can lengthen the heart’s QT interval (which can cause a dangerous rhythm called Torsades de pointes) within 4 weeks or 5 drug half‑lives before and during the study.
- Any prescribed or over‑the‑counter medication without approval.
- Strong inhibitors or inducers of the enzymes CYP3A or transporter P‑gp (for example, St. John’s Wort) within 14–28 days before and during the study.
- HIV protease‑inhibitor medicines or blood thinners (anticoagulants) within 14 days before and during the study.
- Acetaminophen (Tylenol) and ethacrynic acid within 24 hours before and during the study.
Having taken part in another clinical trial within 28 days or 5 drug half‑lives (whichever is longer) before receiving the study drug.
Having previously enrolled in this same study.
Having any significant abnormal findings on a 12‑lead ECG (electrocardiogram) at screening.
Having a known allergy (hypersensitivity) to camizestrant, its inactive ingredients, or to drugs with a similar chemical structure.
Having donated more than 500 mL of blood or having lost a large amount of blood within 56 days before the study drug dose.
Having donated plasma within 28 days before the study drug dose.
Working at the study site or having an immediate family member (spouse or child) who works there, or being a sponsor staff member directly involved with the study.
Being involved in planning or running the study (e.g., staff at the sponsor or study site).
Being judged by the investigator as unlikely to follow the study procedures, restrictions, or requirements.
For participants with liver (hepatic) impairment: having a history of drug abuse within the past 2 years, a positive alcohol or drug test at screening, a positive test for hepatitis B surface antigen or hepatitis C virus, a known HIV infection, evidence of hepatorenal syndrome (a severe liver‑kidney problem) or a kidney function measure (creatinine clearance) less than 60 mL/min, unstable diabetes, or having a transjugular intrahepatic portosystemic shunt (a special liver blood‑flow tube).
For participants with normal liver function: having significant thyroid disease, a history of alcoholism or drug abuse within the past 2 years, a positive alcohol or drug test at screening, a known HIV infection, a positive test for hepatitis B surface antigen or hepatitis C virus, a kidney function measure (creatinine clearance) less than 80 mL/min, low or high blood pressure while lying down (below 90/40 mmHg or above 150/95 mmHg), a low or high pulse rate while lying down (below 50 bpm or above 99 bpm), or a hemoglobin level below the normal range.

Where you can join this trial?

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Other Sites

Site Name	City	Country
Mksvkep Cxudyv Cbeuv Mkibfui Lcbj	Sofia	Bulgaria
Scbzqj Cbvuuzen Ribduzje swgjwn	Nove Mesto	Slovakia
Mtcrejo Cesaox Eqqdmofqof Eanx	Sofia	Bulgaria

Trial status

Country	Status	Recruitment Start
Bulgaria	Not recruiting	01.05.2023
Slovakia	Not recruiting	01.05.2023

Trial locations

Investigated Drugs:

Camizestrant

Camizestrant is an experimental oral medication that works by breaking down estrogen receptors, which can help treat hormone‑driven conditions in post‑menopausal women. In this study, participants take a single film‑coated tablet. The trial is looking at how the drug is absorbed, processed, and cleared in women whose liver function is normal, moderately reduced, or severely reduced. Researchers will also monitor any side effects and how well the drug is tolerated in each group.

moderate or severe hepatic impairment – Hepatic impairment means reduced liver function, which can affect the organ’s ability to process substances and clear waste. In moderate impairment the liver’s capacity is partially decreased, leading to slower clearance of many compounds. In severe impairment the liver’s function is markedly reduced, causing significant accumulation of substances and further loss of metabolic activity. The condition often develops gradually as chronic liver diseases such as hepatitis, fatty liver disease, or cirrhosis cause progressive loss of healthy liver cells. As liver damage advances, the production of essential proteins and detoxification processes continue to decline.

Trial ID:

2022-502277-41-00

Protocol code:

D8532C00002

Trial Phase:

Human Pharmacology (Phase I) – Other

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Effect of moderate or severe liver impairment on the pharmacokinetics, safety and tolerability of camizestrant in post‑menopausal women

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?