Cardiovascular Disease, Healthy Male Subjects
Conditions
Keywords
AZD5718 oral suspension crystalline, AZD5718 oral suspension amorphous, Single ascending dose/multiple ascending dose (SAD/MAD), Placebo-controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics
Brief summary
This is a phase I, randomised, single-blind, placebo-controlled, first-in-human (FIH) single and multiple ascending dose study consisting of two parts (Part A \[SAD\] and Part B \[MAD\]) to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5718 in healthy male subjects
Detailed description
This is a phase I, randomised, single-blind, placebo-controlled, first-in-human (FIH) single and multiple ascending dose study consisting of two parts (Part A \[SAD\] and Part B \[MAD\]) to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5718 in healthy male subjects
Interventions
DRUGAZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A)
Oral suspension single dose
DRUGAZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A)
Single and multiple doses
DRUGAZD5718 placebo oral suspension
Single and multiple doses
DRUGAZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)
Single and multiple doses
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated, written informed consent prior to any study specific procedures 2. Healthy male subjects aged 18 - 50 years, inclusive, with suitable veins for cannulation or repeated venepuncture 3. 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 4. Provision of signed, written and dated informed consent for optional genetic research
Exclusion criteria
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject'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. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of investigational medicinal product (IMP) 4. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results at screening and check-in, as judged by the investigator, including: * Alanine aminotransferase (ALT) \> upper limit of normal (ULN); * Aspartate aminotransferase (AST) \> ULN; * Bilirubin (total) \> ULN; and * Gamma glutamyl transpeptidase (GGT) \> ULN 5. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) 6. Suspicion or known Gilbert's syndrome 7. Abnormal vital signs, after 10 minutes supine rest, at screening and check-in, defined as any of the following: * Systolic blood pressure(BP) (SBP) \< 90mmHg or ≥ 140 mmHg; * Diastolic BP (DBP) \< 50mmHg or ≥ 90 mmHg; and * Pulse \< 45 or \> 85 beats per minute (bpm) 8. Any clinically significant abnormalities (at screening and check-in) in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy 9. Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) \> 450 ms or shortened QTcF \< 340 ms or family history of long QT syndrome, at screening and check-in 10. PR(PQ) interval (ECG interval measured from the onset of the P wave to the onset of the QRS complex) shortening \< 120 ms (PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation), at screening and check-in 11. PR (PQ) interval prolongation (\> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation, at screening and check-in 12. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms. Subjects with QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation, at screening and check-in 13. Known or suspected history of drug abuse, as judged by the investigator 14. Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening 15. Any history of alcohol abuse or excessive intake of alcohol, as judged by the investigator 16. Positive screen for drugs of abuse, alcohol or cotinine (nicotine) at screening or admission to the unit 17. History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5718 18. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator 19. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP 20. 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 prior to the administration of IMP or longer if the medication has a long half-life 21. Plasma donation within 1 month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening 22. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the administration of IMP in this study. The period of exclusion is 3 months after the final dose from a previous study 23. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order 24. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives 25. Judgment by the investigator 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 26. Subjects who are vegans or have medical dietary restrictions 27. Subjects who cannot communicate reliably with the investigator In addition, any of the following is regarded as a criterion for exclusion from the genetic research: 28. Previous bone marrow transplant 29. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | From screening to last followup visit (7-10 days after last dose), up to 6 weeks (Part A) and up to 8 weeks (Part B) | To assess the safety and tolerability of AZD5718 following oral administration of SAD (Part A) and MAD (Part B). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension | Day 1 of Part B | To assess the rate and extent of absorption of AZD5718 by evaluation of the area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess area under the area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUC(0-last)) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 1, Day 9 and Day 10 of Part B | To assess the rate and extent of absorption of AZD5718 by evaluation of the area under the plasma concentration-curve over the dosing interval (AUC(0-τ)) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess observed maximum plasma concentration (Cmax) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 1, Day 9 and Day 10 (Part B only) | To assess the rate and extent of absorption of AZD5718 by evaluation of the observed maximum plasma concentration (Cmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess the time to reach the observed maximum plasma concentration (tmax) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 1, Day 9 and Day 10 (Part B only) | To assess the rate and extent of absorption of AZD5718 by evaluation of the time to reach the observed maximum plasma concentration (tmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess Rate and extent of absorption of AZD5718 by assessment of the half-life associated with terminal slope of a semi-logarithmic plasma concentration-time curve (t½λz) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 1 and Day 10 (Part B only) | To assess the rate and extent of absorption of AZD5718 by evaluation of the half-life associated with terminal slope of a semi-logarithmic plasma concentration-time curve (t½λz) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess rate and extent of absorption of AZD5718 by assessment of the apparent total body clearance after extravascular administration estimated as dose divided by AUC (CL/F) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 1 and Day 10 of Part B | To assess rate and extent of absorption of AZD5718 by assessment of the Rate and extent of absorption of AZD5718 by assessment of CL/F estimated as dose divided by AUC (for Day 1 only) and dose divided by AUCτ on Day 10 following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) | To assess rate and extent of absorption of AZD5718 by assessment of the apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of AUC for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) | To assess the relative bioavailability by AUC between the cohort receiving the crystalline suspension and the corresponding data from the cohort receiving the same dose of the amorphous suspension (Part A only). Crystalline suspension was compared to the reference amorphous suspension. Note: Geometric mean ratios for crystalline/amorphous suspensions were calculated |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess area under the concentration-time curve from time zero extrapolated to infinity and was estimated by AUC(0-last) + Clast/λz (Clast - the last observed quantifiable concentration) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension | Day 1 and Day 9 (Part B only) | To assess rate and extent of absorption of AZD5718 by assessment of the Rate and extent of absorption of AZD5718 by assessment of accumulation ratio for AUC(0-τ) (RAC AUC(0-τ)) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) Accumulation ratio calculated as AUC0-τ Day 10/AUC0-τ Day 1 (first dose) for Part B under fasted condition and presented values for Day 10 |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition | Day 1 and Day 9 (Part B only) | To assess the rate and extent of absorption of AZD5718 by evaluation of accumulation ratio for Cmax (RAC Cmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B). Accumulation ratio calculated as Cmax Day 10/Cmax Day 1 (first dose) for Part B under fasted condition. |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition | At Day 10 (Part B only) | To assess rate and extent of absorption of AZD5718 by assessment of the temporal change parameter in systemic exposure (TCP) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B). TCP calculated as AUCτDay10/AUCDay 1 and presented values for Day 10 |
| Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | At Day 9 and Day 10 (Part B only) | The effect of food was evaluated by the assessment of the PK parameter (Cmax) following multiple daily doses of 180 mg AZD5718 under fasted condition (Part B Day 10) and immediately following a high-fat breakfast (Part B Day 9) |
| Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | Part A pre-dose and pooled intervals up to 24 hours post-dose | To assess urine PK parameter (CumAe0-24) after a single administration of AZD5718 Amorphous suspension in Part A |
| Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | Part A pre-dose and pooled intervals up to 24 hours post-dose | To assess urine PK parameter (Cumfe0-24) estimated by dividing Ae(0-last) by dose after a single administration of AZD5718 Amorphous suspension in Part A |
| Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | Part A pre-dose and pooled intervals up to 24 hours post-dose | To assess the urine PK parameter (CLR) after a single administration of AZD5718 Amorphous suspension in Part A |
| Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose | To assess the urine PK parameter (CumAe0-24) after a single administration of AZD5718 Amorphous suspension in Part B Day 9 |
| Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose | To assess urine PK parameter (Cumfe0-24) estimated by dividing Ae(0-last) by dose after a single administration of AZD5718 Amorphous suspension in Part B Day 9 |
| Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose | To assess the urine PK parameter (CLR) after a single administration of AZD5718 Amorphous suspension in Part B Day 9 |
| Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | Admission to 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose (Part A only) | To assess the change from baseline in the ex vivo stimulated LTB4 production using calcium ionophore in venous blood samples following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only) |
| Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Admission, predose and 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose | To assess the change from baseline in the ex vivo stimulated LTB4 production using calcium ionophore in venous blood samples following multiple administration of AZD5718 Amorphous suspension (Part B only) |
| To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of Cmax for Part A - Amorphous and Crystalline Suspension | At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only) | To assess the relative bioavailability by Cmax between the cohort receiving the crystalline suspension and the corresponding data from the cohort receiving the same dose of the amorphous suspension (Part A only). Crystalline suspension was compared to the reference amorphous suspension. Note: Geometric mean ratios for crystalline/amorphous suspensions were calculated |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted on 96 healthy male participants at a single center: PAREXEL Early Phase Clinical Unit - London. This study consisted of 2 parts: Part A - single ascending dose (SAD) and Part B - multiple ascending dose (MAD).
Pre-assignment details
Screening period was from Day -28 and Day -1. Participants signed informed consent form; demographic data, medical history and concomitant medication details were collected; weight, height and body mass index were measured; inclusion/exclusion criteria were checked, serology and screening of urinary drugs of abuse, alcohol and cotinine were done
Participants by arm
| Arm | Count |
|---|---|
| Part A (Amorphous Suspension) Participants received single dose of oral suspension of AZD5718 in amorphous state at dose levels 25 mg, 50 mg, 100 mg, 300 mg, 600 mg & 1200mg with 6 participants in each dose level | 36 |
| Part A (Crystalline Suspension) Participants received single dose of oral suspension of AZD5718 in crystalline state at dose levels 100 mg & 300 mg with 6 participants in each dose level | 12 |
| Part B (Amorphous Suspension) Participants received multiple daily doses of oral suspension of AZD5718 in amorphous state at dose levels 60 mg, 180 mg, 360 mg & 600 mg with 6 participants in each dose level | 24 |
| Placebo - Part A (Amorphous Suspension) 2 participants per dose level received single dose of placebo in Part A (Amorphous suspension) | 12 |
| Placebo - Part A (Crystalline Suspension) 2 participants per dose level received single dose of placebo in Part A (Crystalline suspension) | 4 |
| Placebo - Part B (Amorphous Suspension) 2 participants per dose level received single dose of placebo in Part B (Amorphous suspension) | 8 |
| Total | 96 |
Baseline characteristics
| Characteristic | Part A (Amorphous Suspension) | Total | Part A (Crystalline Suspension) | Part B (Amorphous Suspension) | Placebo - Part A (Amorphous Suspension) | Placebo - Part A (Crystalline Suspension) | Placebo - Part B (Amorphous Suspension) |
|---|---|---|---|---|---|---|---|
| Age, Continuous Part A (Amorphous Suspension) | 34.3 Years STANDARD_DEVIATION 8.85 | 34.3 Years STANDARD_DEVIATION 8.85 | — | — | — | — | — |
| Age, Continuous Part A (Crystalline Suspension) | — | 33.2 Years STANDARD_DEVIATION 11.64 | 33.2 Years STANDARD_DEVIATION 11.64 | — | — | — | — |
| Age, Continuous Part B (Amorphous Suspension) | — | 35.5 Years STANDARD_DEVIATION 7.32 | — | 35.5 Years STANDARD_DEVIATION 7.32 | — | — | — |
| Age, Continuous Placebo - Part A (Amorphous Suspension) | — | 34.9 Years STANDARD_DEVIATION 10.23 | — | — | 34.9 Years STANDARD_DEVIATION 10.23 | — | — |
| Age, Continuous Placebo - Part A (Crystalline Suspension) | — | 33.3 Years STANDARD_DEVIATION 5.62 | — | — | — | 33.3 Years STANDARD_DEVIATION 5.62 | — |
| Age, Continuous Placebo - Part B (Amorphous Suspension) | — | 38.3 Years STANDARD_DEVIATION 5.31 | — | — | — | — | 38.3 Years STANDARD_DEVIATION 5.31 |
| Body mass index (BMI) Part A (Amorphous Suspension) | 24.71 Kilogram/square meter STANDARD_DEVIATION 3.014 | 24.71 Kilogram/square meter STANDARD_DEVIATION 3.014 | — | — | — | — | — |
| Body mass index (BMI) Part A (Crystalline Suspension) | — | 22.94 Kilogram/square meter STANDARD_DEVIATION 2.265 | 22.94 Kilogram/square meter STANDARD_DEVIATION 2.265 | — | — | — | — |
| Body mass index (BMI) Part B (Amorphous Suspension) | — | 24.56 Kilogram/square meter STANDARD_DEVIATION 2.456 | — | 24.56 Kilogram/square meter STANDARD_DEVIATION 2.456 | — | — | — |
| Body mass index (BMI) Placebo - Part A (Amorphous Suspension) | — | 24.68 Kilogram/square meter STANDARD_DEVIATION 2.764 | — | — | 24.68 Kilogram/square meter STANDARD_DEVIATION 2.764 | — | — |
| Body mass index (BMI) Placebo - Part A (Crystalline Suspension) | — | 26.55 Kilogram/square meter STANDARD_DEVIATION 1.634 | — | — | — | 26.55 Kilogram/square meter STANDARD_DEVIATION 1.634 | — |
| Body mass index (BMI) Placebo - Part B (Amorphous Suspension) | — | 24.14 Kilogram/square meter STANDARD_DEVIATION 1.133 | — | — | — | — | 24.14 Kilogram/square meter STANDARD_DEVIATION 1.133 |
| Height Part A (Amorphous Suspension) | 179.0 Centimeter STANDARD_DEVIATION 6.32 | 179.0 Centimeter STANDARD_DEVIATION 6.32 | — | — | — | — | — |
| Height Part A (Crystalline Suspension) | — | 180.9 Centimeter STANDARD_DEVIATION 6.95 | 180.9 Centimeter STANDARD_DEVIATION 6.95 | — | — | — | — |
| Height Part B (Amorphous Suspension) | — | 178.0 Centimeter STANDARD_DEVIATION 7.07 | — | 178.0 Centimeter STANDARD_DEVIATION 7.07 | — | — | — |
| Height Placebo - Part A (Amorphous Suspension) | — | 176.3 Centimeter STANDARD_DEVIATION 5.33 | — | — | 176.3 Centimeter STANDARD_DEVIATION 5.33 | — | — |
| Height Placebo - Part A (Crystalline Suspension) | — | 174.3 Centimeter STANDARD_DEVIATION 3.3 | — | — | — | 174.3 Centimeter STANDARD_DEVIATION 3.3 | — |
| Height Placebo - Part B (Amorphous Suspension) | — | 175.5 Centimeter STANDARD_DEVIATION 7.37 | — | — | — | — | 175.5 Centimeter STANDARD_DEVIATION 7.37 |
| Race/Ethnicity, Customized Asian | 4 Participants | 11 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 12 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 35 Participants | 91 Participants | 11 Participants | 23 Participants | 12 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Other: Mixed: Black And White | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 69 Participants | 9 Participants | 20 Participants | 9 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 96 Participants | 12 Participants | 24 Participants | 12 Participants | 4 Participants | 8 Participants |
| Weight Part A (Amorphous Suspension) | 79.24 Kilogram STANDARD_DEVIATION 10.982 | 79.24 Kilogram STANDARD_DEVIATION 10.982 | — | — | — | — | — |
| Weight Part A (Crystalline Suspension) | — | 74.89 Kilogram STANDARD_DEVIATION 5.45 | 74.89 Kilogram STANDARD_DEVIATION 5.45 | — | — | — | — |
| Weight Part B (Amorphous Suspension) | — | 77.95 Kilogram STANDARD_DEVIATION 10.369 | — | 77.95 Kilogram STANDARD_DEVIATION 10.369 | — | — | — |
| Weight Placebo - Part A (Amorphous Suspension) | — | 76.70 Kilogram STANDARD_DEVIATION 9.547 | — | — | 76.70 Kilogram STANDARD_DEVIATION 9.547 | — | — |
| Weight Placebo - Part A (Crystalline Suspension) | — | 80.50 Kilogram STANDARD_DEVIATION 2.647 | — | — | — | 80.50 Kilogram STANDARD_DEVIATION 2.647 | — |
| Weight Placebo - Part B (Amorphous Suspension) | — | 74.34 Kilogram STANDARD_DEVIATION 5.532 | — | — | — | — | 74.34 Kilogram STANDARD_DEVIATION 5.532 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 1 / 6 | 3 / 6 | 1 / 6 | 4 / 6 | 1 / 12 | 0 / 6 | 2 / 6 | 1 / 4 | 2 / 6 | 3 / 6 | 2 / 6 | 3 / 6 | 4 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B).
To assess the safety and tolerability of AZD5718 following oral administration of SAD (Part A) and MAD (Part B).
Time frame: From screening to last followup visit (7-10 days after last dose), up to 6 weeks (Part A) and up to 8 weeks (Part B)
Population: All randomized subjects who received at least 1 dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 15 Participants |
| Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 2 Participants |
| Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 10 Participants |
| Placebo - Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 1 Participants |
| Placebo - Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Placebo - Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Placebo - Part A (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Placebo - Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Placebo - Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Placebo - Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Placebo - Part A (Crystalline Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 1 Participants |
| Placebo - Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE with outcome = death | 0 Participants |
| Placebo - Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any SAE (including events with outcome = death) | 0 Participants |
| Placebo - Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE leading to discontinuation of IMP | 0 Participants |
| Placebo - Part B (Amorphous Suspension) | Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B). | Any AE | 4 Participants |
Secondary
Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension
To assess the change from baseline in the ex vivo stimulated LTB4 production using calcium ionophore in venous blood samples following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: Admission to 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose (Part A only)
Population: All subjects who received at least 1 dose of AZD5718 or placebo and who had at least 1 pre-dose and one post-dose measurement of stimulated LTB4 and who had no major protocol deviations thought to impact on the analysis of the PD data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 1.03 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 1.48 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.948 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0.415 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.858 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.874 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.889 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.616 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.443 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.672 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.91 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 1.05 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.124 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0.0234 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.22 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.0177 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.00669 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.553 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.334 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.470 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.877 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.0271 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.560 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0.000518 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.739 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.0213 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 0.813 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.000715 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.000165 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.435 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.000304 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.000249 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.0515 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.000219 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.0000451 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.00116 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 0.379 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.560 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.0698 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.0000318 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.290 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.000106 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 0.0142 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.00100 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 0.00108 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.0632 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 1.36 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 1.20 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.943 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 1.04 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.965 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.70 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.877 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 1.41 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.952 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.930 Nanogram/liter (ng/L) |
| 100 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 1.23 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.472 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0.0634 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.0187 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.638 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.247 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.0449 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.245 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.497 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.04 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.781 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.0267 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.646 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 0.188 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.852 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 0.00880 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.0329 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.369 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.0532 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.00819 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.292 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.940 Nanogram/liter (ng/L) |
| 300 mg - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.04 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 12.0 hours post-dose | 1.50 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 24.0 hours post-dose | 0.986 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 48.0 hours post-dose | 0.893 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 1.0 hours post-dose | 0.833 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 6.0 hours post-dose | 0.842 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 3.0 hours post-dose | 0.647 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 36.0 hours post-dose | 1.31 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 0.5 hours post-dose | 0.934 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 8.0 hours post-dose | 1.39 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 2.0 hours post-dose | 0.841 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of Leukotriene B4 (LTB4) Production Using Calcium Ionophore for Part A -Amorphous and Crystalline Suspension | 4.0 hours post-dose | 0.635 Nanogram/liter (ng/L) |
Secondary
Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension
To assess the change from baseline in the ex vivo stimulated LTB4 production using calcium ionophore in venous blood samples following multiple administration of AZD5718 Amorphous suspension (Part B only)
Time frame: Admission, predose and 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose
Population: All subjects who received at least 1 dose of AZD5718 or placebo and who had at least 1 pre-dose and one post-dose measurement of stimulated LTB4 and who had no major protocol deviations thought to impact on the analysis of the PD data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 2 hours post-dose | 0 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 6 hours post-dose | 0.000109 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 6, pre-dose | 0.472 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 12 hours post-dose | 0.0143 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 7, pre-dose | 0.511 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 11, 24 hours post-dose | 0.194 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 8, pre-dose | 0.583 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 2, pre-dose | 0.654 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 12, 48 hours post-dose | 0.550 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 3, pre-dose | 0.557 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 9, pre-dose | 0.288 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 4, pre-dose | 0.731 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, pre-dose | 0.164 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 1, 12 hours post-dose | 0.116 Nanogram/liter (ng/L) |
| Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 5, pre-dose | 0.421 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 2 hours post-dose | 0.000198 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 2, pre-dose | 0.434 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 12 hours post-dose | 0.00247 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 6 hours post-dose | 0.0000944 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 6, pre-dose | 0.227 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 1, 12 hours post-dose | 0.00171 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 9, pre-dose | 0.0360 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 5, pre-dose | 0.159 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 4, pre-dose | 0.294 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, pre-dose | 0.0266 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 3, pre-dose | 0.203 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 12, 48 hours post-dose | 0.906 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 7, pre-dose | 0.376 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 8, pre-dose | 0.134 Nanogram/liter (ng/L) |
| Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 11, 24 hours post-dose | 0.0901 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 8, pre-dose | 0.00187 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 9, pre-dose | 0.00171 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 2 hours post-dose | 0 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 1, 12 hours post-dose | 0.0000984 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 2, pre-dose | 0.00350 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 3, pre-dose | 0.00609 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 11, 24 hours post-dose | 0.000426 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 4, pre-dose | 0.00328 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, pre-dose | 0.000908 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 12 hours post-dose | 0 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 5, pre-dose | 0.00467 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 6, pre-dose | 0.00242 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 12, 48 hours post-dose | 0.304 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 7, pre-dose | 0.00210 Nanogram/liter (ng/L) |
| Part B (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 6 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 2, pre-dose | 0.000771 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 3, pre-dose | 0.000893 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 12, 48 hours post-dose | 0.0583 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 1, 12 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 4, pre-dose | 0.000152 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 5, pre-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 6, pre-dose | 0.000158 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 7, pre-dose | 0.000195 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 8, pre-dose | 0.000342 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 9, pre-dose | 0.000130 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, pre-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 2 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 6 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 12 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Amorphous Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 11, 24 hours post-dose | 0 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 8, pre-dose | 0.904 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 7, pre-dose | 1.05 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 1, 12 hours post-dose | 1.49 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 6, pre-dose | 0.895 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 5, pre-dose | 0.893 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 4, pre-dose | 0.950 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 6 hours post-dose | 0.921 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 12 hours post-dose | 1.20 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 3, pre-dose | 1.10 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 12, 48 hours post-dose | 1.05 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 11, 24 hours post-dose | 1.20 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, pre-dose | 0.982 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 9, pre-dose | 0.661 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 2, pre-dose | 1.01 Nanogram/liter (ng/L) |
| Placebo - Part A (Crystalline Suspension) | Pharmacodynamic Analysis by ex Vivo Stimulation of LTB4 Production Using Calcium Ionophore for Part B - Amorphous Suspension | Day 10, 2 hours post-dose | 0.812 Nanogram/liter (ng/L) |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A)
To assess urine PK parameter (CumAe0-24) after a single administration of AZD5718 Amorphous suspension in Part A
Time frame: Part A pre-dose and pooled intervals up to 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 206.9 nmol | Standard Deviation 125 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 439.8 nmol | Standard Deviation 85.95 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 1030 nmol | Standard Deviation 449.7 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 5960 nmol | Standard Deviation 2027 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 13610 nmol | Standard Deviation 3850 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 23600 nmol | Standard Deviation 8577 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 292.4 nmol | Standard Deviation 80.5 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted at the Last Sampling Interval (CumAe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 425.9 nmol | Standard Deviation 190.2 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9)
To assess the urine PK parameter (CumAe0-24) after a single administration of AZD5718 Amorphous suspension in Part B Day 9
Time frame: Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 953.0 nmol | Standard Deviation 253.2 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 2219 nmol | Standard Deviation 612 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 13720 nmol | Standard Deviation 612 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Cumulative Amount of Analyte Excreted From 0 to 24 Hours (CumAe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 18920 nmol | Standard Deviation 6717 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9)
To assess urine PK parameter (Cumfe0-24) estimated by dividing Ae(0-last) by dose after a single administration of AZD5718 Amorphous suspension in Part B Day 9
Time frame: Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.7092 Percentage of Dose Excreted | Standard Deviation 0.1884 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.5504 Percentage of Dose Excreted | Standard Deviation 0.1518 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 1.702 Percentage of Dose Excreted | Standard Deviation 0.2911 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 1.408 Percentage of Dose Excreted | Standard Deviation 0.4999 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A)
To assess urine PK parameter (Cumfe0-24) estimated by dividing Ae(0-last) by dose after a single administration of AZD5718 Amorphous suspension in Part A
Time frame: Part A pre-dose and pooled intervals up to 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.3695 Percentage of Dose Excreted | Standard Deviation 0.2232 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.3927 Percentage of Dose Excreted | Standard Deviation 0.07675 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.4598 Percentage of Dose Excreted | Standard Deviation 0.2008 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.8870 Percentage of Dose Excreted | Standard Deviation 0.3017 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 1.013 Percentage of Dose Excreted | Standard Deviation 0.2865 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.8781 Percentage of Dose Excreted | Standard Deviation 0.3191 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.1306 Percentage of Dose Excreted | Standard Deviation 0.03594 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Percentage of Dose Excreted Unchanged Into the Urine From 0 to 24 Hours (Cumfe0-24) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.06339 Percentage of Dose Excreted | Standard Deviation 0.02831 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9)
To assess the urine PK parameter (CLR) after a single administration of AZD5718 Amorphous suspension in Part B Day 9
Time frame: Part B only, Day 9 at pooled 3 hour intervals until 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.6490 Liter/hour | Standard Deviation 0.1029 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.7172 Liter/hour | Standard Deviation 0.07593 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.9831 Liter/hour | Standard Deviation 0.04645 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Multiple Daily Doses Administration of AZD5718 Amorphous Suspension (Part B Day 9) | 0.7368 Liter/hour | Standard Deviation 0.1654 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A)
To assess the urine PK parameter (CLR) after a single administration of AZD5718 Amorphous suspension in Part A
Time frame: Part A pre-dose and pooled intervals up to 24 hours post-dose
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.7241 Liter/hour | Standard Deviation 0.264 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.6221 Liter/hour | Standard Deviation 0.09344 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.6782 Liter/hour | Standard Deviation 1.599 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.6860 Liter/hour | Standard Deviation 0.1634 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.7093 Liter/hour | Standard Deviation 0.1118 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.6206 Liter/hour | Standard Deviation 0.07438 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.4502 Liter/hour | Standard Deviation 0.1043 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of Renal Clearance (CLR) Following a Single Administration of AZD5718 Amorphous and Crystalline Suspension (Part A) | 0.4312 Liter/hour | Standard Deviation 0.07115 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension
To assess rate and extent of absorption of AZD5718 by assessment of the Rate and extent of absorption of AZD5718 by assessment of accumulation ratio for AUC(0-τ) (RAC AUC(0-τ)) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B) Accumulation ratio calculated as AUC0-τ Day 10/AUC0-τ Day 1 (first dose) for Part B under fasted condition and presented values for Day 10
Time frame: Day 1 and Day 9 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension | 1.368 Ratio |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension | 1.387 Ratio |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension | 1.253 Ratio |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for AUC(0-τ) (RAC AUC(0-τ)) for Part B - Amorphous Suspension | 1.444 Ratio |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition
To assess the rate and extent of absorption of AZD5718 by evaluation of accumulation ratio for Cmax (RAC Cmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B). Accumulation ratio calculated as Cmax Day 10/Cmax Day 1 (first dose) for Part B under fasted condition.
Time frame: Day 1 and Day 9 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition | 1.368 Ratio, no units |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition | 1.387 Ratio, no units |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition | 1.253 Ratio, no units |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Accumulation Ratio for Cmax (RAC Cmax) for Part B (Amorphous Suspension) Under Fasted Condition | 1.444 Ratio, no units |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension
To assess rate and extent of absorption of AZD5718 by assessment of the apparent total body clearance after extravascular administration estimated as dose divided by AUC (CL/F) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 157.3 Liters/Hours | Standard Deviation 60.18 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 155.5 Liters/Hours | Standard Deviation 22.31 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 168.1 Liters/Hours | Standard Deviation 74.1 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 80.84 Liters/Hours | Standard Deviation 18.41 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 76.30 Liters/Hours | Standard Deviation 29.08 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 78.88 Liters/Hours | Standard Deviation 31.04 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 324.5 Liters/Hours | Standard Deviation 77.99 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part A - Amorphous and Crystalline Suspension | 714.6 Liters/Hours | Standard Deviation 292.2 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension
To assess rate and extent of absorption of AZD5718 by assessment of the Rate and extent of absorption of AZD5718 by assessment of CL/F estimated as dose divided by AUC (for Day 1 only) and dose divided by AUCτ on Day 10 following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1 and Day 10 of Part B
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 1 | 126.6 Liter/Hour | Standard Deviation 31.39 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 10 | 99.85 Liter/Hour | Standard Deviation 26.4 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 10 | 85.06 Liter/Hour | Standard Deviation 35.38 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 1 | 112.2 Liter/Hour | Standard Deviation 45.1 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 1 | 77.96 Liter/Hour | Standard Deviation 24.8 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 10 | 65.65 Liter/Hour | Standard Deviation 20.14 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 1 | 85.85 Liter/Hour | Standard Deviation 36.98 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F) for Part B - Amorphous Suspension | Day 10 | 63.07 Liter/Hour | Standard Deviation 28.39 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension
To assess rate and extent of absorption of AZD5718 by assessment of the apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 2608 Liters | Standard Deviation 447.6 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 2940 Liters | Standard Deviation 1063 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 3490 Liters | Standard Deviation 2433 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 1770 Liters | Standard Deviation 992.9 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 1264 Liters | Standard Deviation 446.6 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 1189 Liters | Standard Deviation 538.9 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 8801 Liters | Standard Deviation 2072 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Part A - Amorphous and Crystalline Suspension | 14630 Liters | Standard Deviation 5751 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension
To assess the rate and extent of absorption of AZD5718 by evaluation of the area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1 of Part B
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension | 1087 h*nmol/L | Geometric Coefficient of Variation 24.01 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension | 3834 h*nmol/L | Geometric Coefficient of Variation 40.94 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension | 10720 h*nmol/L | Geometric Coefficient of Variation 28.8 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension | 17010 h*nmol/L | Geometric Coefficient of Variation 47.74 |
Comparison: Day 190% CI: [1.08, 1.36]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension
To assess area under the concentration-time curve from time zero extrapolated to infinity and was estimated by AUC(0-last) + Clast/λz (Clast - the last observed quantifiable concentration) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 376.3 h*nmol/L | Geometric Coefficient of Variation 38.09 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 727.0 h*nmol/L | Geometric Coefficient of Variation 15.39 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 1441 h*nmol/L | Geometric Coefficient of Variation 45.26 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 8462 h*nmol/L | Geometric Coefficient of Variation 20.05 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 18810 h*nmol/L | Geometric Coefficient of Variation 42.09 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 35840 h*nmol/L | Geometric Coefficient of Variation 33.71 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 706.7 h*nmol/L | Geometric Coefficient of Variation 24.24 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension | 1006 h*nmol/L | Geometric Coefficient of Variation 43.72 |
90% CI: [1.17, 1.31]
90% CI: [-0.0124, 0.656]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension
To assess area under the area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUC(0-last)) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 264.5 h*nmol/L | Geometric Coefficient of Variation 87.15 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 701.5 h*nmol/L | Geometric Coefficient of Variation 15.83 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 1408 h*nmol/L | Geometric Coefficient of Variation 47.23 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 8395 h*nmol/L | Geometric Coefficient of Variation 20.61 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 18740 h*nmol/L | Geometric Coefficient of Variation 42.13 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 35760 h*nmol/L | Geometric Coefficient of Variation 33.81 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 642.9 h*nmol/L | Geometric Coefficient of Variation 21.55 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension | 933.2 h*nmol/L | Geometric Coefficient of Variation 41.61 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension
To assess the rate and extent of absorption of AZD5718 by evaluation of the area under the plasma concentration-curve over the dosing interval (AUC(0-τ)) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1, Day 9 and Day 10 of Part B
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 1 | 1018 h*nmol/L | Geometric Coefficient of Variation 22.4 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 10 | 1386 h*nmol/L | Geometric Coefficient of Variation 27.4 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 9 | 1441 h*nmol/L | Geometric Coefficient of Variation 24.92 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 1 | 3732 h*nmol/L | Geometric Coefficient of Variation 41.19 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 10 | 5128 h*nmol/L | Geometric Coefficient of Variation 46.9 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 9 | 3312 h*nmol/L | Geometric Coefficient of Variation 33.26 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 9 | 13790 h*nmol/L | Geometric Coefficient of Variation 20.56 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 1 | 10350 h*nmol/L | Geometric Coefficient of Variation 28.84 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 10 | 12760 h*nmol/L | Geometric Coefficient of Variation 31 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 1 | 16290 h*nmol/L | Geometric Coefficient of Variation 48.56 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 10 | 23170 h*nmol/L | Geometric Coefficient of Variation 47.49 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension | Day 9 | 24890 h*nmol/L | Geometric Coefficient of Variation 44.2 |
Comparison: Day 1090% CI: [1.08, 1.38]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10)
The effect of food was evaluated by the assessment of the PK parameter(tmax) following multiple daily doses of 180 mg AZD5718 under fasted condition (Part B Day 10) and immediately following a high-fat breakfast (Part B Day 9)
Time frame: At Day 9 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 3.51 Hours |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 1.00 Hours |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10)
The effect of food was evaluated by the assessment of the PK parameter (Cmax) following multiple daily doses of 180 mg AZD5718 under fasted condition (Part B Day 10) and immediately following a high-fat breakfast (Part B Day 9)
Time frame: At Day 9 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 349.8 nmol/L | Geometric Coefficient of Variation 34.99 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 1243 nmol/L | Geometric Coefficient of Variation 55.23 |
Comparison: Cmax90% CI: [20.98, 37.73]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10)
The effect of food was evaluated by the assessment of the PK parameter (AUC(0-t) following multiple daily doses of 180 mg AZD5718 under fasted condition (Part B Day 10) and immediately following a high-fat breakfast (Part B Day 9)
Time frame: At Day 9 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 3312 h*nmol/L | Geometric Coefficient of Variation 33.26 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Effect of Food Following Administration of 180 mg AZD5718 With Food (Part B Day 9) and Fasted (Part B Day 10) | 5128 h*nmol/L | Geometric Coefficient of Variation 46.9 |
Comparison: AUC(0-τ)90% CI: [54.34, 76.74]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension
To assess Rate and extent of absorption of AZD5718 by assessment of the half-life associated with terminal slope of a semi-logarithmic plasma concentration-time curve (t½λz) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 11.90 Hours | Standard Deviation 5.063 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 13.14 Hours | Standard Deviation 4.684 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 13.30 Hours | Standard Deviation 4.357 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 14.62 Hours | Standard Deviation 5.361 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 11.62 Hours | Standard Deviation 2.198 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 10.41 Hours | Standard Deviation 1.851 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 19.97 Hours | Standard Deviation 6.763 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part A - Amorphous and Crystalline Suspension | 14.18 Hours | Standard Deviation 2.653 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension
To assess the rate and extent of absorption of AZD5718 by evaluation of the half-life associated with terminal slope of a semi-logarithmic plasma concentration-time curve (t½λz) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 1 -From sampling time to 24 hrs; not true t½λz | 7.450 Hours | Standard Deviation 0.8084 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 10 | 11.65 Hours | Standard Deviation 0.7718 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 10 | 11.29 Hours | Standard Deviation 1.432 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 1 -From sampling time to 24 hrs; not true t½λz | 5.489 Hours | Standard Deviation 1.168 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 1 -From sampling time to 24 hrs; not true t½λz | 5.920 Hours | Standard Deviation 0.5085 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 10 | 9.156 Hours | Standard Deviation 1.014 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 1 -From sampling time to 24 hrs; not true t½λz | 6.799 Hours | Standard Deviation 2.036 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Half-life Associated With Terminal Slope of a Semi-logarithmic Plasma Concentration-time Curve (t½λz) for Part B - Amorphous Suspension | Day 10 | 10.23 Hours | Standard Deviation 3.144 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension
To assess observed maximum plasma concentration (Cmax) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 27.14 nmol/L | Geometric Coefficient of Variation 75.96 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 81.62 nmol/L | Geometric Coefficient of Variation 36.39 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 170.3 nmol/L | Geometric Coefficient of Variation 54.86 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 2358 nmol/L | Geometric Coefficient of Variation 32.89 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 5052 nmol/L | Geometric Coefficient of Variation 45.82 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 6875 nmol/L | Geometric Coefficient of Variation 34.94 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 54.62 nmol/L | Geometric Coefficient of Variation 28.35 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension | 80.24 nmol/L | Geometric Coefficient of Variation 39.73 |
90% CI: [1.43, 1.66]
90% CI: [0.0315, 0.669]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension
To assess the rate and extent of absorption of AZD5718 by evaluation of the observed maximum plasma concentration (Cmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1, Day 9 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 1 | 167.3 nmol/L | Geometric Coefficient of Variation 19.81 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 10 | 219.8 nmol/L | Geometric Coefficient of Variation 31.93 |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 9 | 225.4 nmol/L | Geometric Coefficient of Variation 31.7 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 1 | 846.9 nmol/L | Geometric Coefficient of Variation 48 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 10 | 1243 nmol/L | Geometric Coefficient of Variation 55.23 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 9 | 349.8 nmol/L | Geometric Coefficient of Variation 34.99 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 9 | 3372 nmol/L | Geometric Coefficient of Variation 22.69 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 1 | 2561 nmol/L | Geometric Coefficient of Variation 31.72 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 10 | 3209 nmol/L | Geometric Coefficient of Variation 40.01 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 1 | 4933 nmol/L | Geometric Coefficient of Variation 47.63 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 10 | 5693 nmol/L | Geometric Coefficient of Variation 59.95 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part B - Amorphous Suspension | Day 9 | 5297 nmol/L | Geometric Coefficient of Variation 43.52 |
Comparison: For Day 190% CI: [1.34, 1.63]
Comparison: Day 1090% CI: [1.25, 1.6]
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition
To assess rate and extent of absorption of AZD5718 by assessment of the temporal change parameter in systemic exposure (TCP) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B). TCP calculated as AUCτDay10/AUCDay 1 and presented values for Day 10
Time frame: At Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition | 1.280 Ratio, no units |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition | 1.349 Ratio, no units |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition | 1.211 Ratio, no units |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Temporal Change Parameter in Systemic Exposure (TCP) for Part B (Amorphous Suspension) Under Fasted Condition | 1.385 Ratio, no units |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension
To assess the time to reach the observed maximum plasma concentration (tmax) following a single administration of AZD5718 Amorphous and Crystalline suspension (Part A only)
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 2.99 Hours | Full Range 75.96 |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.02 Hours | Full Range 36.39 |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.00 Hours | Full Range 54.86 |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.00 Hours | Full Range 32.89 |
| Placebo - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.00 Hours | Full Range 45.82 |
| Placebo - Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.51 Hours | Full Range 34.94 |
| 100 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 3.00 Hours | Full Range 28.35 |
| 300 mg - Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part A - Amorphous and Crystalline Suspension | 1.98 Hours | Full Range 39.73 |
Secondary
Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension
To assess the rate and extent of absorption of AZD5718 by evaluation of the time to reach the observed maximum plasma concentration (tmax) following a single AZD5718 dose on Day 1 and multiple daily dosing on Days 9 or 10 under fasted conditions (Part B)
Time frame: Day 1, Day 9 and Day 10 (Part B only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 1 | 0.76 Hours |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 10 | 0.50 Hours |
| Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 9 | 1.00 Hours |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 1 | 1.00 Hours |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 10 | 1.00 Hours |
| Part A (Crystalline Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 9 | 3.51 Hours |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 9 | 0.99 Hours |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 1 | 1.01 Hours |
| Part B (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 10 | 1.00 Hours |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 1 | 1.00 Hours |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 10 | 1.49 Hours |
| Placebo - Part A (Amorphous Suspension) | Rate and Extent of Absorption of AZD5718 by Assessment of the Time to Reach the Observed Maximum Plasma Concentration (Tmax) for Part B - Amorphous Suspension | Day 9 | 2.00 Hours |
Secondary
To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of AUC for Part A - Amorphous and Crystalline Suspension
To assess the relative bioavailability by AUC between the cohort receiving the crystalline suspension and the corresponding data from the cohort receiving the same dose of the amorphous suspension (Part A only). Crystalline suspension was compared to the reference amorphous suspension. Note: Geometric mean ratios for crystalline/amorphous suspensions were calculated
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of AUC for Part A - Amorphous and Crystalline Suspension | 49.1 h*nmol/L | 90% Confidence Interval 2433 |
| Part A (Crystalline Suspension) | To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of AUC for Part A - Amorphous and Crystalline Suspension | 11.9 h*nmol/L | 90% Confidence Interval 992.9 |
Secondary
To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of Cmax for Part A - Amorphous and Crystalline Suspension
To assess the relative bioavailability by Cmax between the cohort receiving the crystalline suspension and the corresponding data from the cohort receiving the same dose of the amorphous suspension (Part A only). Crystalline suspension was compared to the reference amorphous suspension. Note: Geometric mean ratios for crystalline/amorphous suspensions were calculated
Time frame: At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)
Population: All subjects in the safety analysis set for whom at least one dose of AZD5718 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (Amorphous Suspension) | To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of Cmax for Part A - Amorphous and Crystalline Suspension | 32.1 nmol/L | 90% Confidence Interval 2433 |
| Part A (Crystalline Suspension) | To Evaluate the Relative Bioavailability Between the Amorphous and Crystalline Form of AZD5718 (Part A) by Assessment of Cmax for Part A - Amorphous and Crystalline Suspension | 3.40 nmol/L | 90% Confidence Interval 992.9 |