High Risk Coronary Artery Disease
Conditions
Keywords
Pharmacokinetics (PK), Bioavailability (BA), Safety, Tolerability, Healthy Volunteers
Brief summary
This study is a randomized, open-label, 5-period, 5-treatment, single-dose, single-center, crossover study to estimate the effect of AZD5718 on the pharmacokinetics (PK) of rosuvastatin, and to assess the relative bioavailability of AZD5718 oral suspension vs AZD5718 immediate release (IR) Tablet Formulation and the Food Effect of AZD5718 in Healthy Volunteers. The study will be performed at a single study center.
Detailed description
The study will comprise: * A Screening period of maximum 28 days; * Five treatment periods during which subjects will be resident from the morning on the day before dosing with the IMP (Day -1) until at least 48 hours after dosing; discharge will be on the morning of Day 3, and * A Follow-up Visit within 7 to 10 days after the last administration of the IMPs. * There will be a minimum of a 7 days washout between each treatment period. Each subject will receive 5 treatments. The following treatments will be given: * Treatment A: 10 mg rosuvastatin tablet alone (fasting state) * Treatment B: 10 mg rosuvastatin tablet + 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state) * Treatment C: 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state) * Treatment D: 200 mg of AZD5718 oral suspension 50 mg/mL (fasting state) * Treatment E: 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fed state) Each subject will be involved in the study for approximately 8 weeks.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
For inclusion in the study, subjects should fulfill the following criteria: 1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male and/or female subjects (of non childbearing potential) aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture. 3. Females must have a negative pregnancy test at the Screening Visit and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria 3.1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range. 3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral ophorectomy or bilateral salpingectomy but excluding bilateral tubal ligation. 4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive. 5. Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study.
Exclusion criteria
Subjects will not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under plasma concentration-time curve from time zero to infinity (AUC) of Rosuvastatin | Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose | Assessment of AUC of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers. |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-last)] of Rosuvastatin | Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose | Assessment of AUC(0-last) of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers. |
| Maximum observed plasma concentration (Cmax) of Rosuvastatin | Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose | Assessment of Cmax of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-last) of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of AUC(0-last) of AZD5718. |
| Cmax of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of Cmax of AZD5718. |
| tmax of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of tmax of AZD5718. |
| t½ of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of t½ of AZD5718. |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of CL/F of AZD5718. |
| Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½) of Rosuvastatin - | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose. (Only Treatment A and B) | Assessment of t½ of rosuvastatin. |
| Adverse events (AEs) | Screening, Day -1 and Days 1 to 3 (treatment periods 1 to 5) and follow up visit (7-10 days post final dose) | Assessment of the safety in terms of the incidences of the AEs. |
| Vital signs (systolic and diastolic blood pressure, pulse rate and body temperature) | Screening, Day -1, Pre-dose, 48 h post-dose and Follow-up visit (7-10 days post final dose) | Assessment of the safety in terms of the Vital signs (systolic and diastolic blood pressure, pulse rate). |
| Electrocardiogram (ECG) | Screening, Day -1, Pre-dose, 48 h post-dose and Follow-up visit (7-10 days post final dose) | Assessment of the safety in terms of the ECG. |
| Physical examination | Screening, Day -1 (brief), 48 h (brief) post-dose | Assessment of the safety in terms of the physical examination. |
| Laboratory assessments (hematology, clinical chemistry and urinalysis). | Screening, Day -1 (only limited clinical laboratory evaluations will be performed), Pre-dose, 48 h post-dose and Follow-up Visit (7-10 days post final dose) | Assessment of the safety in terms of the Clinical laboratory assessments (hematology, clinical chemistry and urinalysis). |
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of Vz/F of AZD5718. |
| Time to reach maximum observed plasma concentration (tmax) of rosuvastatin | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose. (Only Treatment A and B) | Assessment of tmax of rosuvastatin. |
| AUC of AZD5718 | Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose (Only Treatment B, C, D, and E) | Assessment of AUC of AZD5718. |
Countries
United Kingdom
Outcome results
None listed