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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
12
Research Site
London, United Kingdom
Area under plasma concentration-time curve from time zero to infinity (AUC) of Rosuvastatin
Assessment of AUC of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.
Time frame: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-last)] of Rosuvastatin
Assessment of AUC(0-last) of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.
Time frame: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose
Maximum observed plasma concentration (Cmax) of Rosuvastatin
Assessment of Cmax of rosuvastatin when administered alone and in combination with AZD5718 in healthy volunteers.
Time frame: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½) of Rosuvastatin -
Assessment of t½ of rosuvastatin.
Time frame: 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)
Time to reach maximum observed plasma concentration (tmax) of rosuvastatin
Assessment of tmax of rosuvastatin.
Time frame: 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)
AUC of AZD5718
Assessment of AUC of AZD5718.
Time frame: 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)
AUC(0-last) of AZD5718
Assessment of AUC(0-last) of AZD5718.
Time frame: 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)
Cmax of AZD5718
Assessment of Cmax of AZD5718.
Time frame: 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)
tmax of AZD5718
Assessment of tmax of AZD5718.
Time frame: 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)
t½ of AZD5718
Assessment of t½ of AZD5718.
Time frame: 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)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD5718
Assessment of CL/F of AZD5718.
Time frame: 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)
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD5718
Assessment of Vz/F of AZD5718.
Time frame: 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)
Adverse events (AEs)
Assessment of the safety in terms of the incidences of the AEs.
Time frame: Screening, Day -1 and Days 1 to 3 (treatment periods 1 to 5) and follow up visit (7-10 days post final dose)
Vital signs (systolic and diastolic blood pressure, pulse rate and body temperature)
Assessment of the safety in terms of the Vital signs (systolic and diastolic blood pressure, pulse rate).
Time frame: Screening, Day -1, Pre-dose, 48 h post-dose and Follow-up visit (7-10 days post final dose)
Electrocardiogram (ECG)
Assessment of the safety in terms of the ECG.
Time frame: Screening, Day -1, Pre-dose, 48 h post-dose and Follow-up visit (7-10 days post final dose)
Physical examination
Assessment of the safety in terms of the physical examination.
Time frame: Screening, Day -1 (brief), 48 h (brief) post-dose
Laboratory assessments (hematology, clinical chemistry and urinalysis).
Assessment of the safety in terms of the Clinical laboratory assessments (hematology, clinical chemistry and urinalysis).
Time frame: 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)
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