An Open-Label, Fixed Sequence Study in Healthy Post Menopausal Female Subjects to Assess the Pharmacokinetics of Camizestrant (AZD9833) When Administered Alone and in Combination With Itraconazole
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Camizestrant
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 50 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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:
- •Subject has a positive test for SARS-CoV-2 prior to admission.
- •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.
- •Subject has been previously hospitalized with COVID-19 infection within the last 12 months.
Arms & Interventions
Treatment Arm
Subjects 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.
Intervention: Camizestrant (Drug)
Treatment Arm
Subjects 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.
Intervention: Itraconazole (Drug)
Outcomes
Primary Outcomes
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Camizestrant
Time Frame: Day 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 Camizestrant
Time Frame: Day 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 Camizestrant
Time Frame: Day 1 to Day 4 (Period 1 and Period 3)
To assess the effect of Itraconazole on AUCinf of Camizestrant.
Secondary Outcomes
- 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 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])