Single-dose capivasertib testing in people with moderate liver impairment

A Phase I, Single-dose, Non-randomized, Open-label, Parallel Group Study to Assess the Pharmacokinetics and Safety of Capivasertib in Participants With Moderate Hepatic Impairment

This trial will test how a single oral dose of capivasertib is processed and tolerated in adults with moderate liver impairment compared with people who have normal liver function.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 2 sites (Rialto, California and 1 other locations)
• Trial ID: NCT07343960 on ClinicalTrials.gov

What this trial studies

This is a single-dose, open-label, non-randomized, parallel-group pharmacokinetic and safety study comparing participants with moderate hepatic impairment (Child-Pugh class B) to participants with normal hepatic function. Eligible participants will be resident at the site from the day before dosing through Day 4, receive one oral dose of capivasertib on Day 1, and return for a follow-up visit on Days 9–11. The study will collect blood samples for pharmacokinetic analysis and monitor safety and tolerability through clinical assessments and laboratory tests. The goal is to characterize how liver impairment affects drug exposure and short-term safety signals to inform dosing recommendations.

Who should consider this trial

Good fit: Adults with documented moderate hepatic impairment (Child-Pugh class B, total bilirubin ~1.5–3× ULN) who meet weight/BMI limits, are non-smokers, can tolerate repeated blood draws, and can stay at the site for the residential period are ideal candidates.

Not a fit: People with severe liver impairment (Child-Pugh C), unstable liver disease, active smoking within 3 months, or those unable to remain at the site for inpatient monitoring are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, results could inform safer dosing or monitoring guidelines for people with moderate liver impairment who may need capivasertib.

How similar studies have performed: Dedicated single-dose pharmacokinetic and safety studies in patients with hepatic impairment are a common regulatory approach and have successfully guided dosing for many oncology drugs, and capivasertib has prior safety and PK data from oncology trials though this focused moderate‑impairment study is specific.

Eligibility criteria

Key Inclusion Criteria:

* Body weight of at least 50 kg and Body Mass Index (BMI) of between ≥ 18 up to ≤ 40 kg/m2.
* Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Participants must have suitable veins for cannulation or repeated venipuncture.
* Non-smoker, defined as a participant who has not smoked previously or who has discontinued smoking or the use of other nicotine/nicotine-containing products at least 3 months before the Screening Visit.
* Supporting documents confirming the participant's hepatic impairment must be available (a liver biopsy is preferable but not mandatory); participants must be classified by the Investigator as Child Pugh class B.
* Participants must meet National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG) classification of total bilirubin 1.5 to 3\*upper limit of normal (ULN) and any Aspartate aminotransferase/transaminase (AST) for moderate hepatic impairment.
* Stable hepatic impairment
* For participants with normal hepatic function, Bilirubin \< 1.5 × ULN, alanine aminotransferase (ALT), AST, albumin, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) \< 1.2 × ULN. Creatinine \< ULN. White blood cell count \> lower limit of normal (LLN).

Key Exclusion Criteria:

* Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, significant aneurysm, renal transplant and active bleeding diseases) which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
* Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of capivasertib.
* History of primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
* Active tuberculosis infection.
* Known Human Immunodeficiency Virus (HIV) infection, active hepatitis B or C infection, positive hepatitis C antibody, and/or positive hepatitis B virus surface antigen.
* Clinically significant abnormalities of glucose metabolism as defined by HemoglobinA1c (HbA1c) ≥ 8.0% (63.9 mmol/mol) at screening.
* Moderate or severe renal dysfunction according to age-related creatinine clearance estimated using CKD-EPI formula (i.e., creatinine clearance less than 60 mL/min).
* Fluctuating or rapidly deteriorating hepatic function.
* Presence of a hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.
* Severe portal hypertension or surgical porto-systemic shunts.
* Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
* Clinically relevant hepatic encephalopathy (Grade 3 or more).
* Severe ascites.
* Esophageal variceal bleeding (unless banded) within the past 2 months.
* Post-liver transplantation.

Where this trial is running

Rialto, California and 1 other locations

• Research Site — Rialto, California, United States (Recruiting)
• Research Site — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Moderate Hepatic Impairment; Hepatic function; Anti-cancer agent; Pyrrolopyrimidine-derived compound; Liver metabolism; Serine/threonine protein kinase AKT; Pharmacokinetics