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A Study to Assess the Pharmacokinetics of Camizestrant (AZD9833) When Administered Alone and in Combination With Itraconazole

Phase 1
Completed
Conditions
Healthy Subjects
Interventions
Registration Number
NCT05551897
Lead Sponsor
AstraZeneca
Brief Summary

This study will be conducted in healthy post-menopausal female subjects to assess the pharmacokinetics (PK) of Camizestrant (AZD9833) when administered alone and in combination with Itraconazole.

Detailed Description

This open-label, fixed sequence study will comprise of:

* A screening period of 28 days;

* A fixed sequence of three treatment period:

Treatment Period 1: Camizestrant only, Treatment Period 2: Itraconazole only, Treatment Period 3: Camizestrant and Itraconazole in combination.

• A Follow-up Visit at 7 to 14 days after the last Camizestrant PK sample in Period 3.

There will be a washout period of 7 to 10 days between Period 1 and Period 2. Each subject will be involved in the study for approximately 8 or 9 weeks.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
14
Inclusion Criteria
  • Healthy post-menopausal female subjects aged 50 to 70 years with suitable veins for cannulation or repeated venipuncture

  • Subjects must be post-menopausal by fulfilling the following criterion:

    a. Post-menopausal defined as amenorrhea for at least 12 months or more without an alternative medical or surgical cause and confirmed by an FSH result of ≥ 30 IU/L.

  • Have a body mass index (BMI) 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) from screening, and for 2 weeks after last administration of the study drug.

Exclusion Criteria
  • History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study

  • 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 clinically significant cardiovascular, chronic respiratory, neurological, or psychiatric disorder

  • 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

  • Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the study drug.

  • Any clinically significant abnormal findings in vital signs or 12-lead Electrocardiogram (ECG).

  • Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human Immunodeficiency Virus (HIV) antibody.

  • Known or suspected history of drug or alcohol abuse.

  • History of significant allergy or hypersensitivity.

  • Current smokers or those who have smoked or used nicotine products (including e-cigarettes and nicotine replacement products) within the 3 months prior to screening.

  • Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to first dose in the study.

  • Have any active indication for therapeutic anticoagulation, and/or having taken an anticoagulant within 14 days of beginning the study.

  • Any of the following signs or confirmation of COVID-19 infection:

    1. Subject has a positive test for SARS-CoV-2 prior to admission.
    2. Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or at admission.
    3. Subject has been previously hospitalized with COVID-19 infection within the last 12 months.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment ArmCamizestrantSubjects will receive a single oral dose of Camizestrant on Day 1 of treatment period 1. Following washout period of 7 to 10 days, subjects will receive Itraconazole on Days 1, 2, and 3 of treatment period 2, and single oral dose of Camizestrant plus a dose of Itraconazole on Day 1, followed by Itraconazole alone on Day 2 and Day 3 of treatment period 3.
Treatment ArmItraconazoleSubjects will receive a single oral dose of Camizestrant on Day 1 of treatment period 1. Following washout period of 7 to 10 days, subjects will receive Itraconazole on Days 1, 2, and 3 of treatment period 2, and single oral dose of Camizestrant plus a dose of Itraconazole on Day 1, followed by Itraconazole alone on Day 2 and Day 3 of treatment period 3.
Primary Outcome Measures
NameTimeMethod
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of CamizestrantDay 1 to Day 4 (Period 1 and Period 3)

To assess the effect of Itraconazole on AUClast of Camizestrant.

Maximum observed plasma (peak) drug concentration (Cmax) of CamizestrantDay 1 to Day 4 (Period 1 and Period 3)

To assess the effect of Itraconazole on Cmax of Camizestrant.

Area under plasma concentration time curve from zero to infinity (AUCinf) of CamizestrantDay 1 to Day 4 (Period 1 and Period 3)

To assess the effect of Itraconazole on AUCinf of Camizestrant.

Secondary Outcome Measures
NameTimeMethod
Number of subjects with adverse events leading to the discontinuation of study drug (DAEs)From Day 1 (period 1) up to follow-up visit (7 to 14 days after last Pharmacokinetic Sample) [approximately 9 weeks]

Number of subjects who discontinue the study drug due to adverse events will be assessed.

Number of subjects with adverse events (AEs) and serious adverse events (SAEs)From Screening (Day -28 to Day -2) up to follow-up visit (7 to 14 days after last Pharmacokinetic Sample) [approximately 9 weeks]

Safety and tolerability of Camizestrant alone and in combination with Itraconazole will be assessed.

Trial Locations

Locations (1)

Research Site

🇬🇧

Harrow, United Kingdom

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