Study to Investigate Hepatic Impairment on PK, Safety, Tolerability of Camizestrant in Post-Menopausal Female Subjects

NCT05790304 | Completed Phase 1 FDA Drug

• 2 other identifiers: D8532C000022022-502277-41-00
• Study Type: interventional
• Target: 22
• Locations: 3 countries
• Sites: 4

Brief Summary

This will be a Phase I, multicentre, single-dose, non-randomized, open-label, parallel-group study to examine the PK, safety, and tolerability of camizestrant 75 mg in post-menopausal female participants with moderate or severe hepatic impairment compared with post-menopausal female participants with normal hepatic function. Participants will be enrolled within the following groups based on their CP classification score as determined at screening:

• Group 1: Matched-control healthy participants with normal hepatic function.
• Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).
• Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15).

Conditions

Hepatic Impairment

Keywords

hepatic impairment; Moderate; Severe

Outcome Measures

Primary Outcomes (8)

• PK parameters Cmax

  Cmax: maximum concentration

  5 days

• PK parameters tmax

  tmax : time to maximum concentration

  5 days

• PK parameters AUClast,

  area under the concentration-time curve (AUC) from zero to the last measurable concentration (AUClast)

  5 days

• PK parameters AUCinf.;

  area under the concentration-time curve (AUC) from zero to infinity (AUCinf)

  5 days

• PK parameters tlast

  tlast: time of the last measurable concentration

  5 days

• PK parameters t1/2λz

  t1/2λz: apparent terminal elimination half-life

  5 days

• PK parameters CL/F

  CL/F: apparent clearance;

  5 days

• PK parameters Vz/F.

  Vz/F: apparent volume of distribution.

  5 days

Secondary Outcomes (2)

• Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

  4.5 weeks

• Number of participants with an AE causally related to IMP leading to study discontinuation

  4.5 weeks

Study Arms (3)

Group 1

OTHER

Matched-control healthy participants with normal hepatic function.

Drug: Camizestrant

Group 2

OTHER

Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).

Drug: Camizestrant

Group 3

OTHER

Participants with severe hepatic impairment (CP Class C, score of 10 to 15).

Drug: Camizestrant

Interventions

Camizestrant DRUG

Camizestrant 75 mg tablets. Experimental drug.

Also known as: AZD9833

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 50 Years - 75 Years
• Gender Eligibility Details: Female, post-menopausal.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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

You may not qualify if:

• 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:
• 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.
• Use of any prescribed or non-prescribed medication
• 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.
• Human immunodeficiency virus protease inhibitor, anticoagulant within 14 days prior to the dose of study drug and throughout the study.
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

San Antonio, Texas, 78215, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

Sofia, 1612, Bulgaria

Location

Research Site

Bratislava, 831 01, Slovakia

Location

Related Links

• D8532C00002\_CSR Synopsis\_redacted
• astrazenecaclinicaltrails.com study results

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

AZD9833

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be enrolled within the following groups based on their CP classification score as determined at screening: * Group 1: Matched-control healthy participants with normal hepatic function. * Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). * Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15).

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: March 30, 2023
• Study Start: February 20, 2023
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (2); SL (1); BU (1)