Healthy Participants
Conditions
Keywords
Drug-drug interaction, Pharmacokinetics, Breast Cancer Resistance Protein
Brief summary
The purpose of the study is to assess the effect of capivasertib on the pharmacokinetics (PK) of oral rosuvastatin in healthy participants.
Detailed description
This study is an open-label, fixed-sequence, drug-drug interaction study of orally administered rosuvastatin in the presence and absence of capivasertib in healthy participants. The study will comprise: 1. A Screening Period of maximum 28 days. 2. Two Treatment Periods * Period 1: Participants will receive single oral dose of rosuvastatin. * Period 2: Participants will receive two single oral doses of capivasertib administered 12 hours apart, with the first capivasertib dose being concomitantly administered with a single oral dose of rosuvastatin. 3. A final Follow-up Visit within 7 to 10 days after the last study intervention administration. There will be a minimum washout period of at least 7 days between the first dose of rosuvastatin (in Treatment Period 1) and the second dose of rosuvastatin (in Treatment Period 2).
Interventions
DRUGCapivasertib
Capivasertib will be administered orally twice in Period 2.
DRUGRosuvastatin
Rosuvastatin will be administered orally once in both Period 1 and Period 2.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Healthy male and/or female participants with suitable veins for cannulation or repeated venipuncture. 2. Body Mass Index (BMI) between 18 and 32 kg/m² inclusive and weigh at least 50 kg and no more than 150 kg inclusive. 3. All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit and must not be lactating. 4. Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: 1. Postmenopausal (≥12 months of amenorrhea + hormone confirmation). 2. Irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy, and/or bilateral salpingectomy (excluding tubal ligation) at least 6 months prior to screening. 5. Male participants must be vasectomized (at least 6 months prior to screening), with documented post-procedural medical assessment of surgical success. 6. Participants must be willing to use study-specific contraceptive methods. Key
Exclusion criteria
1. History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study. 2. History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically important illness, medical/surgical procedure, or trauma. 4. Any clinically significant skin abnormalities that are chronic or currently active. 5. Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results. 6. Any positive result on screening for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus antibody (HCV antibody), or Human Immunodeficiency Virus (HIV). 7. Any clinically significant abnormalities in blood lipid profiles (triglycerides, high-density lipoprotein, low-density lipoprotein, and total cholesterol). 8. Any clinically significant abnormalities in glucose metabolism, including: 1. Diagnosis of type I or II diabetes mellitus (irrespective of management), 2. Fasting blood glucose ≥ 100 mg/dL, or 3. Hemoglobin A1c \> 5.7% after at least 8 hours of fasting at screening. 9. Any clinically significant abnormal findings in vital signs. 10. Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) and defined as Sick sinus syndrome, arrhythmia, prolonged QTcF \> 450 ms, family history of long QT syndrome, persistent or intermittent bundle branch block, and atrio-ventricular block Grade II or III. 11. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months. 12. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. 13. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to capivasertib or rosuvastatin or history of hypersensitivity to any component of the finished dosage form of capivasertib. 14. Plasma donation or any blood donation/blood loss prior to the Screening Visit. 15. Participants who have previously received capivasertib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (AUCinf) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (AUClast) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Maximum observed drug concentration (Cmax) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (Cmax) of rosuvastatin when administered orally alone and in combination with capivasertib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of AUCinf (R AUCinf) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (R AUCinf) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Ratio of AUClast (R AUClast) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (R AUClast) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Ratio of Cmax (R Cmax) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (R Cmax) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Terminal elimination half-life (t½λz) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (t½λz) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Terminal elimination rate constant (λz) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (λz) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| Time to reach maximum observed concentration (tmax) of rosuvastatin | Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3 | To evaluate the PK (tmax) of rosuvastatin when administered orally alone and in combination with capivasertib. |
| AUClast of capivasertib | Period 2: Day 1 to Day 3 | To evaluate the PK (AUClast) of capivasertib following oral dosing. |
| Concentration at the end of a dosing interval (Ctrough) of capivasertib | Period 2: Day 1 to Day 3 | To evaluate the PK (Ctrough) of capivasertib following oral dosing. |
| Cmax of capivasertib | Period 2: Day 1 to Day 3 | To evaluate the PK (Cmax) of capivasertib following oral dosing. |
| Number of participants with adverse events (AEs) and serious AEs | From Screening (Day -30 to Day -2) to follow-up visit (Day 10) | To assess the safety and tolerability of capivasertib when administered with rosuvastatin. |
| Change in serum bilirubin levels | Day 1 (pre-capivasertib dose) to Day 3 (post-capivasertib dose) | To evaluate the effect of capivasertib dosing on total, conjugated, and unconjugated bilirubin levels. |
Countries
United States
Outcome results
None listed