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AZD5718

Phase 2

Coronary Artery Disease | Small molecule | Cardiovascular |AstraZeneca PLC|Last Updated: Jun 30, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials2
Total Enrollment161
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03317002AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD).PHASE2 COMPLETED 129Oct 30, 2017Apr 8, 2020Jun 30, 20219 Denmark, Finland +1
NCT03400488A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Japanese MenPHASE1 COMPLETED 32Jan 16, 2018Jun 12, 2018Jun 15, 20181 United States
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Study Endpoints
Primary Endpoints
Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
Baseline and 4 weeks

Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine

Number of patients with Adverse Events (AEs) due to AZD5817
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the adverse events as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. Adverse Events will be collected from the start of randomization throughout the treatment period up to and including the follow-up visit. Serious adverse events (SAEs) will be recorded from the time of informed consent.

Supine vital sign (Systolic Blood pressure [BP])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the vital sign as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.

Supine vital sign (pulse rate)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Number of participants with abnormal findings in electrocardiograms (ECGs) (safety ECGs, digital ECGs [dECG])
From baseline up to follow-up (7 to 10 days post-(final) dose). For dECG: Days 1 to 12

To assess any clinically important abnormalities in the cardiovascular system functioning as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. A 12-lead 10-second safety ECG will be performed with the Schiller Cardiovit CS-200 recorder immediately following all scheduled dECGs. 12-lead continuous dECG will be recorded over at least 5 minutes with the Schiller Cardiovit CS-200 recorder and transmitted to the AstraZeneca central dECG repository, according to AstraZeneca ECG Center´s standard procedures for settings, recording, and transmission of dECGs. For dECG, QTcF (QT interval corrected for heart rate using Fridericia's formula) will be calculated as QTcF =(QT\*(RR/1000)\^(-1/3)), where RR (the time between corresponding points on 2 consecutive R waves on ECG) is presented in milliseconds. Heart rate (HR) will also be calculated, based on the RR interval.

Number of participants with abnormal cardiac telemetry
From baseline up to Day 10

To assess any clinically important abnormalities in the cardiovascular system functioning (heart beat/rythm) using 2-lead real-time telemetry ECG as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The telemetry monitoring system will be reviewed by the Investigator or research nurse and paper printouts of any clinically important events will be stored as source data.

Number of participants with abnormal findings in physical examinations
From baseline up to follow-up (7 to 10 days post-(final) dose)

To assess any clinically important abnormal findings in physical conditions as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses. The complete physical examinations include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations include an assessment of the general appearance, skin, cardiovascular system, respiratory and abdomen. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an adverse event.

Laboratory assessment: Hematology (leukocyte count)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the leukocyte count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Supine vital sign (diastolic BP)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the vital sign as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (sodium)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (sodium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Urinalysis (glucose)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess urinalysis (glucose) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Red blood cell [RBC] count)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the RBC count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Hemoglobin [Hb])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the Hb as a criterion of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Hematocrit [HCT])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the HCT as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Mean corpuscular volume [MCV])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the MCV as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Mean corpuscular hemoglobin [MCH])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the MCH as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Mean corpuscular hemoglobin concentration [MCHC])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the MCHC as a variable of safety and tolerability variable of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (potassium)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (potassium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (urea)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (urea) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (creatinine)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (albumin)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (albumin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (calcium)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (calcium) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (phosphate)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (phosphate) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (glucose (fasting))
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (glucose (fasting)) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (insulin)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (insulin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (fibrinogen)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (fibrinogen) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (thyroid-stimulating hormone)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (thyroid-stimulating hormone) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Urinalysis (blood)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess urinalysis (blood) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell \[WBC\], casts \[cellular, granular, hyaline\]).

Laboratory assessment: Urinalysis (protein)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess urinalysis (protein) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses. If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts \[cellular, granular, hyaline\]).

Laboratory assessment: Urinalysis (urine creatinine)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess urinalysis (urine creatinine) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Differential Count)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the differential count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Platelets)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the platelets as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Hematology (Reticulocytes absolute count)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the reticulocytes absolute count as a variable of safety and tolerability of AZD5718 following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (High sensitivity-C-reactive protein [CRP])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (CRP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Free T4)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (Free T4) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Alkaline phosphatase [ALP])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (ALP) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Alanine aminotransferase [ALT])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (ALT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Aspartate aminotransferase [AST])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (AST) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Gamma glutamyl transpeptidase [GGT])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (GGT) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Total Bilirubin)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (total bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Unconjugated bilirubin)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (unconjugated bilirubin) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Glutamate dehydrogenase)
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (glutamate dehydrogenase) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Laboratory assessment: Clinical chemistry (Lactate dehydrogenase [LDH])
Change from baseline up to follow-up (7 to 10 days post-(final) dose)

To assess the clinical chemistry value (LDH) as a variable of safety and tolerability of AZD5718, following oral administration of single and multiple ascending doses.

Secondary Endpoints
Change From Baseline in Creatinine-normalized u-LTE4 at Week 12
Baseline and 12 weeks
Change From Baseline in CFVR at Week 12
Baseline and 12 weeks
Change From Baseline in CFVR at Week 4
Baseline and 4 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
AZD5718 Dose AEXPERIMENTALAZD5718 Dose A once daily
AZD5718 Dose BEXPERIMENTALAZD5718 Dose B once daily
PlaceboPLACEBO_COMPARATORMatching placebo once daily
AZD5718EXPERIMENTALRandomized subjects will receive orally once daily dose of AZD5718 oral suspension on Day 1 (SAD) and MAD from Days 3 to 10. On Day 2, no dose will be given. These procedures will be repeated in all cohorts.
Interventions
NameTypeDescription
AZD5718DRUGOral dose of AZD5718 (tablet)
PlaceboDRUGMatching placebo (tablet)
AZD5718 oral suspensionDRUGIn all cohorts, randomized subjects will receive orally AZD5718 oral suspension SAD (60 mg) on Day 1 and MAD (180 mg, 360 mg and 600 mg) from Days 3 to 10. On Day 2, no dose will be given. In total each subject will receive 9 doses of AZD5718.
Placebo matching AZD5817 oral suspensionOTHERIn all cohorts, randomized subjects will receive orally placebo matching AZD5718 oral suspension on Day 1 and from Days 3 to 10. On Day 2, no dose will be given.
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites9

Inclusion Criteria: * Males and females of non-childbearing potential * Age ≥18 to ≤75 * Body Mass Index (BMI) ≥18 to ≤35 kg/m2 * CAD patients, here defined as: ACS 7-28 days prior to study randomization (ACS defined as STEMI, non STEMI event documented by Electrocardiogram (ECG), cardiac enzymes ...

Countries:DenmarkFinlandSwedenUnited States
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