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

NCT06547164 | Completed Phase 1

• 1 other identifier: D8532C00006
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted in order to determine the effect of repeated oral doses of camizestrant on the pharmacokinetics (PK) of midazolam and to determine the effect of repeated oral titrated doses of carbamazepine on the PK of camizestrant in healthy post-menopausal female participants.

Conditions

Healthy Participants

Keywords

Midazolam; Camizestrant; Carbamazepine; Post-menopausal; Estrogen receptor (ER) positive disease; Breast Cancer; Cytochrome P450, family 3, subfamily A (CYP3A)

Outcome Measures

Primary Outcomes (6)

• Part A: Area under concentration-time curve from time 0 to infinity (AUCinf) of midazolam

  To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants.

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Area under concentrationcurve from time 0 to the last quantifiable concentration (AUClast) of midazolam

  To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants.

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Maximum observed plasma (peak) drug concentration (Cmax) of midazolam

  To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants.

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part B: Area under concentration-time curve from time 0 to infinity (AUCinf) of camizestrant

  To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants.

  Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)

• Part B: Area under concentrationcurve from time 0 to the last quantifiable concentration (AUClast) of camizestrant

  To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants.

  Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)

• Part B: Maximum observed plasma (peak) drug concentration (Cmax) of camizestrant

  To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants.

  Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)

Secondary Outcomes (12)

• Part A: Time to reach maximum observed concentration (tmax) of midazolam

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Terminal elimination half-life (t½λz) of midazolam

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Terminal rate constant (λz) of midazolam

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Apparent total body clearance (CL/F) of midazolam

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

• Part A: Apparent volume of distribution based on the terminal phase (Vz/F) of midazolam

  Period 1 (Day 1) and Period 3 (Day 7 to Day 8)

Study Arms (2)

Part A: Midazolam + Camizestrant

EXPERIMENTAL

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; Drug: Camizestrant

Part B: Camizestrant + Carbamazepine

EXPERIMENTAL

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 15 with single oral dose of camizestrant on Day 13 with PK sampling on Day 16 in Period 2.

Drug: Camizestrant; Drug: Carbamazepine

Interventions

Midazolam DRUG

Midazolam will be administered orally.

Part A: Midazolam + Camizestrant

Camizestrant DRUG

Camizestrant will be administered orally.

Also known as: AZD9833

Part A: Midazolam + Camizestrant; Part B: Camizestrant + Carbamazepine

Carbamazepine DRUG

Carbamazepine will be administered orally.

Part B: Camizestrant + Carbamazepine

Eligibility Criteria

• Age: 50 Years - 70 Years
• Gender Eligibility Details: Healthy post-menopausal female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Midazolam; AZD9833; Carbamazepine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Study Design

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

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 9, 2024
• Study Start: August 27, 2024
• Primary Completion: August 20, 2025
• Study Completion: August 20, 2025
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer 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 anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

GB (1)