Healthy Subjects
Conditions
Keywords
Pharmacokinetics, Breast Cancer, Selective Estrogen Receptor Degrader (SERD), ER-Positive, HER2- Negative Breast Cancer
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.
Interventions
DRUGCamizestrant
Subjects will be administered a single oral dose of Camizestrant on Day 1 of treatment period 1 and treatment period 3.
DRUGItraconazole
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.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 70 Years
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: 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United Kingdom
Outcome results
None listed