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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:
Each subject will receive 5 treatments. The following treatments will be given:
Each subject will be involved in the study for approximately 8 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | 10 mg rosuvastatin tablet alone (fasting state) |
|
| Treatment B | Experimental | 10 mg rosuvastatin tablet + 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state) |
|
| Treatment C | Experimental | 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fasting state) |
|
| Treatment D | Experimental | 200 mg of AZD5718 oral suspension 50 mg/mL (fasting state) |
|
| Treatment E | Experimental | 200 mg of AZD5718 IR tablet (2 x 100 mg tablet) (fed state) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5718 IR tablet | Drug |
| ||
| AZD5718 oral suspension |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 h post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½) of Rosuvastatin - | Assessment of 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) |
| Time to reach maximum observed plasma concentration (tmax) of rosuvastatin |
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Inclusion Criteria:
For inclusion in the study, subjects should fulfill the following criteria:
Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male and/or female subjects (of non childbearing potential) aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
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.
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.
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 exclusion criteria are fulfilled:
20. Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
21. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order In addition, the following is considered a criterion for the exclusion from the optional genetic component of the study: 22. Previous bone marrow transplant. 23. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.
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| Name | Affiliation | Role |
|---|---|---|
| Dr. Muna Albayaty, MBChB, MSc, MFPM | PAREXEL Early Phase Clinical Unit London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31793171 | Derived | Ericsson H, Nelander K, Heijer M, Kjaer M, Lindstedt EL, Albayaty M, Forte P, Lagerstrom-Fermer M, Skrtic S. Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability. Clin Pharmacol Drug Dev. 2020 Apr;9(3):411-421. doi: 10.1002/cpdd.756. Epub 2019 Dec 2. |
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| Drug |
|
| Rosuvastatin tablet | Drug |
|
Assessment of 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) |
| AUC of AZD5718 | Assessment of 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) |
| AUC(0-last) of AZD5718 | Assessment of 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) |
| Cmax of AZD5718 | Assessment of 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) |
| tmax of AZD5718 | Assessment of 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) |
| t½ of AZD5718 | Assessment of 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) |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD5718 | Assessment of 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) |
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD5718 | Assessment of 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) |
| Adverse events (AEs) | Assessment of the safety in terms of the incidences of the AEs. | 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). | 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. | 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. | 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). | 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) |
| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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