A Study to Assess the Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers

A Randomized, 6-period, 6-treatment, Single-dose, Open-label, Single-center, Crossover Study to Assess the Relative Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers

In this study, the relative bioavailability of different formulations of AZD5718 will be determined in order to compare it with the formulation used in a previous Phase 2a study and confirm appropriate drug exposure. This study consist of 2 parts. In Part 1, 5 different formulations of AZD5718 would be provided to the participant in fasting condition in a randomized order. After evaluation of Part 1 a single formulation would be selected for dosing in fed condition in Part 2. Each participant will be involved in the study for approximately 5 to 6 weeks. Fourteen participants will be randomized to ensure at least 10 evaluable participants at the end of the last treatment period.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Form 1 of AZD5718 tablets; Drug: Form 2 of AZD5718 tablets; Drug: Form 3 of AZD5718 tablets; Drug: Form 4 of AZD5718 tablets; Drug: Form 5 of AZD5718 tablets; Drug: Selected form (Form 2 - 5) of AZD5718 tablets

Detailed Description

This is a Randomized, 6-period, 6-treatment, Single-dose, Open-label, Single-center, Crossover, phase I Study to Assess the Relative Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers. In this study, the relative bioavailability of different formulations of AZD5718 will be determined in order to compare it with the formulation used in a previous Phase 2a study and confirm appropriate drug exposure. The optimal pharmacokinetic (PK) profile of AZD5718 is currently not known but working hypothesis is that a flatter PK profile will deliver the same efficacy at a lower dose/exposure compared to a fluctuating AZD5718 profile. Thus, formulations with different release rates will be evaluated. Potential food effect of a selected formulation would be determined in order to provide appropriate dose and dosing instructions for further development of AZD5718. This study would consist of 2 parts. In Part 1, 5 different formulations of AZD5718 would be provided to the participants in fasting condition in a randomized order. After evaluation of Part 1 a single formulation would be selected for dosing in fed condition in Part 2. Part 1 of the study will be an open-label, randomized, 5-period, 5-treatment, single dose crossover study in 14 healthy participants (males and females of non-childbearing potential), performed at a single study center to ensure that at least 10 participants are evaluable. Each participant would be randomized to 1 of 10 treatment sequence according to a Williams design to receive the 5 treatments as following: Form 1 of AZD5718 tablets, Treatment B: Form 2 of AZD5718 tablets, Treatment C: Form 3 of AZD5718 tablets, Treatment D: Form 4 of AZD5718 tablets, and Treatment E: Form 5 of AZD5718 tablets. Participants will receive 1 treatment per treatment period. During each treatment period, participants would be dosed following an overnight fast of at least 10 hours. No fluids will be allowed apart from water which can be given until 2 hours before administration of the investigational medicinal product (IMP) and then from 1 hours after administration of the IMP. The dose would be administered with 240 mL of water. A standard meal would be given 4 hours after administration of the IMP. Participants should not lie fully supine (unless specified for certain assessments) for 4 hours after dosing. After completion the PK evaluation in Part 1, the formulation for Part 2 would be selected. At least 10 participants from Part 1 will be included in Part 2, to ensure that at least 8 participants are evaluable. For each participant included in Part 2, there would be minimum period of at least 2 weeks between the last dose of IMP in Part 1 and the dose of IMP in Part 2. During the treatment period in Part 2, participants would be dosed with the selected formulation of IMP with food. Participants would fast at least 10 hours prior to receiving the test meal. Participants should start the recommended meal 30 minutes prior to administration of the IMP. Participants would be required to consume the meal in 25 minutes; however, the IMP should be administered 30 minutes after start of the meal with 240 mL of water. No fluids would be allowed apart from water which can be given until 1 hour before administration of the IMP and then from 2 hours after administration of the IMP. Each participant will be involved in the study for approximately 5 to 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, HA1 3UJ
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated, written informed consent before any study specific procedures.
2. Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.

3. Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria 3.1. Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range.

   3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not 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 described in this protocol.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at-risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
2. History or presence of gastrointestinal (GI), hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
3. Participants with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.
4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
5. Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results, at screening and/or admission to the study unit as judged by the PI.
6. Any clinically significant abnormal findings in vital signs at screening, as judged by the PI.
7. Any clinically significant abnormalities on 12-lead ECG at screening and/or admission to the study unit, as judged by the PI.
8. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
9. Known of suspected Gilbert's syndrome and known or suspected history of drug abuse, as judged by the PI.

10. Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest.

    Note: Participants consented and screened, but not randomized in this study or a previous phase I study, are not excluded.

11. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months before screening.
12. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718.
13. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months before screening.
14. Positive screen for drugs of abuse or cotinine (screening only) at screening or on each admission to the study center or positive screen for alcohol on each admission to the study center.
15. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks before the first administration of IMP.
16. Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks before the first administration of IMP or longer if the medication has a long half life.
17. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.
18. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
19. Subjects who have previously received AZD5718.
20. Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent 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.
22. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; The participant will be administered with Form 1 of AZD5718 tablets with an overnight fast of at least 10 hours.	Drug: Form 1 of AZD5718 tablets; The participants will be dosed with Form 1 of AZD5718 following an overnight fast of at least 10 hours.
Experimental: Treatment B; The participant will be administered with Form 2 of AZD5718 tablets with an overnight fast of at least 10 hours.	Drug: Form 2 of AZD5718 tablets; The participants will be dosed with Form 2 of AZD5718 following an overnight fast of at least 10 hours.
Experimental: Treatment C; The participant will be administered with Form 3 of AZD5718 tablets with an overnight fast of at least 10 hours.	Drug: Form 3 of AZD5718 tablets; The participants will be dosed with Form 3 of AZD5718 following an overnight fast of at least 10 hours.
Experimental: Treatment D; The participant will be administered with Form 4 of AZD5718 tablets with an overnight fast of at least 10 hours.	Drug: Form 4 of AZD5718 tablets; The participants will be dosed with Form 4 of AZD5718 following an overnight fast of at least 10 hours.
Experimental: Treatment E; The participant will be administered with Form 5 of AZD5718 tablets with an overnight fast of at least 10 hours.	Drug: Form 5 of AZD5718 tablets; The participants will be dosed with Form 5 of AZD5718 following an overnight fast of at least 10 hours.
Experimental: Treatment F; The participant will be administered with selected form (one of Form 2-5) of AZD5718 tablets 30 minutes after start of the meal.	Drug: Selected form (Form 2 - 5) of AZD5718 tablets; The participant will be administered with selected form (one of Form 2-5) of AZD5718 tablets 30 minutes after start of the meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve (AUC) of AZD5718	To assess the pharmacokinetics (PK) parameter AUC to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
AUC from time zero to time of last quantifiable concentration (AUC[0-t]) of AZD5718	To assess the PK parameter AUC(0-t)to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Observed maximum plasma concentration (Cmax) of AZD5718	To assess the PK parameter Cmax to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Observed plasma concentration at 24 hours post dose (C24) of AZD5718	To assess the PK parameter C24 to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	24 hour post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of AZD5718 in fed and fasted conditions	To assess the ratio of Cmax of a selected AZD5718 formulation when administered in fed and fasted conditions and relative bioavailability of the tested formulations.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
C24 of AZD5718 in fed and fasted conditions	To assess the ratio of C24 of a selected AZD5718 formulation when administered in fed and fasted conditions and relative bioavailability of the tested formulations.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
AUC(0-t) of AZD5718 in fed and fasted conditions	To assess the ratio of AUC(0-t) of a selected AZD5718 formulation when administered in fed and fasted conditions and relative bioavailability of the tested formulations.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
AUC of AZD5718 in fed and fasted conditions	To assess the ratio of AUC of a selected AZD5718 formulation when administered in fed and fasted conditions and relative bioavailability of the tested formulations.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Number of participants with adverse events	All adverse events will be coded using MedDRA vocabulary, and will be listed for each subject.	From randomization throughout the treatment period (Day 1 to 3) and follow-up Visit (Day 5 to 7) assessed maximum upto 6 weeks.
Assessment of systolic blood pressure	To assess the systolic blood pressure as a criteria of safety and tolerability.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose].
Assessment of diastolic blood pressure	To assess the Diastolic blood pressure as a criteria of safety and tolerability.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose].
Assessment of pulse rate	To assess Pulse rate as a criteria of safety and tolerability.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose].
Assessment of 12-lead electrocardiogram (ECG)	To assess the ECG as a criteria of safety and tolerability. A 10 second 12 lead ECG will be obtained after 10 minutes supine rest.	At screening (From Day -28 to Day -2 - Part 1); 5 to 7 days post final dose (Part 2).
Assessment of physical examination	Assessment of physical examinations will include an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose].
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) of AZD5718	To assess PK parameter t½λz to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Time to reach maximum observed plasma concentration (Tmax) of AZD5718	To assess the PK parameter Tmax to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD5718	To assess the PK parameter CL/F to evaluate the relative bioavailability of different formulations of AZD5718 and compare with the formulation (Form 1 of AZD5718 tablets) used in the Phase 2a clinical study.	At pre dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36 and 48 hours post dose.
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (Hematology)- white blood cell (WBC) count	Safety and tolerability of AZD5718 by assessment of WBC count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- red blood cell (RBC) count	Safety and tolerability of AZD5718 by assessment of RBC count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- haemoglobin (HB)	Safety and tolerability of AZD5718 by assessment of HB.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- hematocrit (HCT)	Safety and tolerability of AZD5718 by assessment of HCT.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- platelets	Safety and tolerability of AZD5718 by assessment of platelets.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- reticulocytes absolute count	Safety and tolerability of AZD5718 by assessment of reticulocytes absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- mean corpuscular hemoglobin (MCH)	Safety and tolerability of AZD5718 by assessment of MCH.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (hematology)- mean corpuscular hemoglobin concentration (MCHC)	Safety and tolerability of AZD5718 by assessment of MCHC.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- creatinine	Safety and tolerability of AZD5718 by assessment of creatinine.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- creatine kinase	Safety and tolerability of AZD5718 by assessment of creatine kinase.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- total bilirubin	Safety and tolerability of AZD5718 by assessment of total bilirubin.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- unconjugated bilirubin	Safety and tolerability of AZD5718 by assessment of unconjugated bilirubin.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- alkaline phosphatase	Safety and tolerability of AZD5718 by assessment of alkaline phosphatase.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- aspartate aminotransferase (AST)	Safety and tolerability of AZD5718 by assessment of AST.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- gamma glutamyl transpeptidase (GGT)	Safety and tolerability of AZD5718 by assessment of GGT.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- albumin	Safety and tolerability of AZD5718 by assessment of albumin.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- potassium	Safety and tolerability of AZD5718 by assessment of potassium.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- sodium	Safety and tolerability of AZD5718 by assessment of sodium.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (clinical chemistry)- calcium	Safety and tolerability of AZD5718 by assessment of calcium.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- C-reactive protein	Safety and tolerability of AZD5718 by assessment of C-reactive protein.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical Laboratory evaluations (clinical chemistry)- urea	Safety and tolerability of AZD5718 by assessment of urea.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- phosphate	Safety and tolerability of AZD5718 by assessment of phosphate.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- glucose (fasting)	Safety and tolerability of AZD5718 by assessment of glucose (fasting).	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations- urinalysis (blood)	Safety and tolerability of AZD5718 by assessment of urinalysis (blood). If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell [WBC], casts [cellular, granular, hyaline]).	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations- urinalysis (glucose)	Safety and tolerability of AZD5718 by assessment of urinalysis (glucose).	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Mean corpuscular volume (MCV)	Safety and tolerability of AZD5718 by assessment of MCV.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- Alanine aminotransferase (ALT)	Safety and tolerability of AZD5718 by assessment of ALT	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (clinical chemistry)- Thyroxine 4 (T4)	Safety and tolerability of AZD5718 by assessment of T4.	At screening (From Day -28 to Day-2)
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations(clinical chemistry)- Thyroid stimulating hormone (TSH)	Safety and tolerability of AZD5718 by assessment of TSH.	At screening (From Day -28 to Day-2)
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations(clinical chemistry)- Follicle stimulating hormone (FSH)	Safety and tolerability of AZD5718 by assessment of FSH in female participants.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Neutrophils absolute count	Safety and tolerability of AZD5718 by assessment of neutrophils absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Lymphocytes absolute count	Safety and tolerability of AZD5718 by assessment of lymphocytes absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Monocytes absolute count	Safety and tolerability of AZD5718 by assessment of monocytes absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Basophils absolute count	Safety and tolerability of AZD5718 by assessment of basophils absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations- urinalysis (protein)	Safety and tolerability of AZD5718 by assessment of urinalysis (protein). If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]
Safety and tolerability of AZD5718 by assessment of clinical laboratory evaluations (hematology)- Eosinophils absolute count	Safety and tolerability of AZD5718 by assessment of eosinophils absolute count.	[Part 1 - At screening (From Day -28 to Day-2); Treatment period 1 (Day-1), Treatment period 1 to 5 (Day 1 to 3)] and [Part 2- At Day-1, Day 1 to 3, 5 to 7 days post final dose]

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel
• Investigators: Principal Investigator: Pablo Forte Soto, MD, Parexel Early Phase Clinical Unit London

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2018
• Primary Completion (Actual): April 18, 2018
• Study Completion (Actual): April 18, 2018

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: bioavailability; vasoactive leukotrienes by leukocytes
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: D7550C00005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No