A Study to Investigate the Pharmacokinetics of Midazolam after Repeated Doses of Camizestrant (AZD9833) and to Investigate the Pharmacokinetics of Camizestrant when Administered Alone and in Combination with Carbamazepine in Healthy Post-Menopausal Female Participants

Study identifier:D8532C00006

ClinicalTrials.gov identifier:NCT06547164

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

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

Medical condition

Healthy Participants

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Midazolam, Camizestrant, Carbamazepine

Sex

Female

Estimated Enrollment

Study type

Interventional

Age

50 Years - 70 Years

Date

Study Start Date: 27 Aug 2024

Estimated Primary Completion Date: 23 Feb 2025

Estimated Study Completion Date: 23 Feb 2025

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2024 by AstraZeneca

Collaborators

Inclusion and exclusion 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.

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Part A: Midazolam + Camizestrant Participants will receive a single oral dose of midazolam on Day 1 in Period 1, followed by oral dose of camizestrant OD from Day 2 to Day 6 in Period 2, and then single oral dose of midazolam with camizestrant on Day 7 with PK sampling on Day 7 to Day 8 in Period 3.	Drug: Midazolam Midazolam will be administered orally. Drug: Camizestrant Camizestrant will be administered orally. Other Name: AZD9833
Experimental: Part B: Camizestrant + Carbamazepine Participants will receive a single oral dose of camizestrant on Day 1 with PK sampling on Day 1 to Day 4 in Period 1, followed by low oral doses of carbamazepine BID on Day 4 to Day 6, mid oral doses of carbamazepine BID on Day 7 to Day 9 and high oral doses of carbamazepine BID on Day 10 to Day 24 with single oral dose of camizestrant on Day 22 with PK sampling on Day 25 in Period 2.	Drug: Camizestrant Camizestrant will be administered orally. Other Name: AZD9833 Drug: Carbamazepine Carbamazepine will be administered orally.

Arms

Assigned Interventions

Experimental: Part A: Midazolam + Camizestrant
Participants will receive a single oral dose of midazolam on Day 1 in Period 1, followed by oral dose of camizestrant OD from Day 2 to Day 6 in Period 2, and then single oral dose of midazolam with camizestrant on Day 7 with PK sampling on Day 7 to Day 8 in Period 3.

Drug: Midazolam
Midazolam will be administered orally.

Drug: Camizestrant
Camizestrant will be administered orally.

Other Name: AZD9833

Experimental: Part B: Camizestrant + Carbamazepine
Participants will receive a single oral dose of camizestrant on Day 1 with PK sampling on Day 1 to Day 4 in Period 1, followed by low oral doses of carbamazepine BID on Day 4 to Day 6, mid oral doses of carbamazepine BID on Day 7 to Day 9 and high oral doses of carbamazepine BID on Day 10 to Day 24 with single oral dose of camizestrant on Day 22 with PK sampling on Day 25 in Period 2.