Investigating how camizestrant affects midazolam and carbamazepine in healthy post-menopausal women

A Phase I, Open-label, 2 Part, Fixed Sequence Study to Assess the Effect of Co-administration of Camizestrant (AZD9833) on the Pharmacokinetics of Midazolam Exposure (CYP3A4/5 Substrate) and of Carbamazepine (CYP3A4/5 Inducer) on Camizestrant Exposure in Healthy Post Menopausal Female Participants

This study is testing how the drug camizestrant affects the way midazolam works and how carbamazepine changes the way camizestrant works in healthy post-menopausal women.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 50 Years to 70 Years
• Sex: Female
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 1 site (Harrow)
• Trial ID: NCT06547164 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the pharmacokinetics of midazolam when administered alongside camizestrant and to assess how carbamazepine influences the pharmacokinetics of camizestrant in healthy post-menopausal female participants. The study is structured in two parts: Part A focuses on the interaction between camizestrant and midazolam, while Part B examines the interaction between carbamazepine and camizestrant. Participants will undergo a series of treatment periods with monitoring of drug levels and effects. The study is designed to provide insights into drug interactions that may inform future treatments.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy post-menopausal women aged 50 years and older with a suitable body mass index.

Not a fit: Patients with a history of clinically significant diseases or those with gastrointestinal, hepatic, or renal disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of drug interactions, leading to safer and more effective medication regimens for patients.

How similar studies have performed: While this study explores specific drug interactions, similar pharmacokinetic studies have shown success in understanding drug metabolism and interactions.

Eligibility criteria

Inclusion Criteria:

* Healthy post-menopausal female participants with suitable veins for cannulation or repeated venipuncture.
* Female participants must be post-menopausal as confirmed at the Screening Visit. Post-menopausal defined as amenorrhoea for at least 12 months or more without an alternative medical or surgical cause and confirmed by a follicle stimulating hormone (FSH) result of ≥ 30 Internation units/liter (IU/L).
* Have a body mass index between 19 and 35 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
* Must agree to not use warfarin or phenytoin (and other coumarin-derived vitamin K antagonist anticoagulants) during the study, and for 2 weeks after last administration of study intervention.

Exclusion Criteria:

* History of any clinically important disease or disorder.
* History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* History of any clinically significant cardiovascular, chronic respiratory disease, haematological, neurological or psychiatric disorder.
* History of acute pulmonary insufficiency marked neuromuscular respiratory weakness, obsessional states, phobic states, sleep apnoea syndrome, and unstable myasthenia gravis.
* Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
* Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis results.
* Any relevant history or known risk factors of QT prolongation or have received drugs known to prolong QT interval.
* Any positive result for serum Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV).
* History of or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to camizestrant or the formulation excipients.
* Presence of any contraindication to the probe substrate carbamazepine.
* Presence of any contraindication to midazolam.
* Have any active indication for therapeutic anticoagulation, and/or having taken an anticoagulant within 14 days of Screening Visit.
* Part B only: Participants identified to carry human leukocyte antigen (HLA)-A\*3101 and/or HLA-B\*1502 allele.
* Participants with bone marrow suppression or a history of bone marrow suppression or aplastic anaemia.
* History of or ongoing clinically significant visual disturbances including but not limited to visual hallucinations, migraine with visual symptoms, blurred vision, frequent floaters/flashes associated with other symptoms such as dizziness.
* Participants with family history of glaucoma or closed angle glaucoma or participants who are currently on anticholinergic medications.
* Participants with an anticipated need for major surgery and/or any surgery requiring general anaesthesia during the participation in the study.
* Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Where this trial is running

Harrow

• Research Site — Harrow, United Kingdom (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Healthy Participants; Midazolam; Camizestrant; Carbamazepine; Post-menopausal; Estrogen receptor positive disease; Breast Cancer; Cytochrome P450, family 3, subfamily A