A Study to Assess the Pharmacokinetics of Camizestrant (AZD9833) When Administered Alone and in Combination With Itraconazole
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This open-label, fixed sequence study will comprise of:
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A screening period of 28 days;
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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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Camizestrant
Subjects will be administered a single oral dose of Camizestrant on Day 1 of treatment period 1 and treatment period 3.
Other Names:
Drug: Itraconazole
Subjects will be administered Itraconazole twice a day on Day 1 and once daily on Day 2 and Day 3 of treatment period 2, and once daily on Day 1, 2 and 3 of treatment period 3.
|
Outcome Measures
Primary Outcome Measures
- Area under plasma concentration time curve from zero to infinity (AUCinf) of Camizestrant [Day 1 to Day 4 (Period 1 and Period 3)]
To assess the effect of Itraconazole on AUCinf of Camizestrant.
- Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Camizestrant [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 [Day 1 to Day 4 (Period 1 and Period 3)]
To assess the effect of Itraconazole on Cmax of Camizestrant.
Secondary Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy post-menopausal female subjects aged 50 to 70 years with suitable veins for cannulation or repeated venipuncture
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Subjects must be post-menopausal by fulfilling the following criterion:
- 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.
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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.
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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:
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History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study
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History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
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History of clinically significant cardiovascular, chronic respiratory, neurological, or psychiatric disorder
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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
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Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the study drug.
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Any clinically significant abnormal findings in vital signs or 12-lead Electrocardiogram (ECG).
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Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human Immunodeficiency Virus (HIV) antibody.
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Known or suspected history of drug or alcohol abuse.
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History of significant allergy or hypersensitivity.
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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.
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Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to first dose in the study.
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Have any active indication for therapeutic anticoagulation, and/or having taken an anticoagulant within 14 days of beginning the study.
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Any of the following signs or confirmation of COVID-19 infection:
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Subject has a positive test for SARS-CoV-2 prior to admission.
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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.
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Subject has been previously hospitalized with COVID-19 infection within the last 12 months.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- AstraZeneca
- Parexel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D8532C00003
- 2022-002011-35