Coronary artery disease
Conditions
Interventions
Product Name: AZD5718 100mg Film-coated Tablet
Product Code: AZD5718
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: AZD5718
Other descriptive name: NA
Concent
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients should fulfil the following criteria: 1. Males and females: a. Males must be surgically sterile or using an acceptable method of contraception b. Females must be of non-childbearing potential confirmed at screening by fulfilling one of the following criteria a) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range, b) documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 2. Age =18 to =75 3. BMI =18 to =35 kg/m2 4. CAD patients, here defined as: a. ACS 7-28 days prior to study randomization (ACS defined as STEMI, non STEMI event documented by ECG, cardiac enzymes [troponin] and angiogram) b. Possible post procedure LAD stenosis is =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1 Alanine aminotransferase (ALT) >2 x ULN (i.e., above the normal range) at visit 2, cirrhosis, recent hepatitis, or positive screening test for hepatitis B (hepatitis B surface antigen) or hepatitis C 2 Uncontrolled Type 1 or Type 2 diabetes defined as haemoglobin A1c (HbA1c) Diabetes Control and Complications Trial (DCCT)> 9% or International Federation of Clinical Chemistry (IFCC) >74.9 mmol/mol 3 Patients with atrial fibrillation (chronic or current) or history of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia or sick sinus syndrome or AV blockage degree 2-3 4 Patients with pacemaker 5 Prior coronary artery by-pass graft (CABG) to LAD 6 Left ventricle ejection fraction < 30% 7 Unacceptable level of angina despite maximal medical therapy or unstable angina at entry Canadian Cardiovascular Society (CCS) = 3 (Visit 1 or Visit 2) 8 Stroke within the previous 6 months from ACS or ongoing treatment with Persantin or Asasantin 9 Planned treatment with zileuton, leukotriene receptor antagonists (e.g. montelukast), coumadin or steroids during trial 10 Planned statin therapy dose regimen changes during trial 11 Chronic use of anticoagulants on therapeutic dose (not including thrombosis prophylaxis) during the study 12 Planned additional cardiac intervention (e.g., PCI, CABG) within next 6 months 13 NYHA class III-IV heart failure at discharge or hospitalization for exacerbation of chronic heart failure within the previous 3 months from ACS 14 Previously known severe renal disease (CKD stage 4 or 5) or previously known creatinine clearance calculated by Cockcroft Gault equation <30 ml/min*m2 15 Aortic or mitral valvular disease or valvular disease classified as severe 16 Known allergy to adenosine 17 Known elevated intracranial pressure 18 Heart rate < 40 bpm 19 Systolic blood pressure < 90 mmHg 20 Asthma or COPD with strong reactive component in judgment of investigator 21 Treatment with dipyridamole, theophyllamine, fluvoxamine, rifampicin, fenytoin or carbamazepine 22 Inability to comply with the study protocol 23 History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class as study drugs 24 Patients unable to give their consent or communicate reliably with the investigator or vulnerable patients e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order 25 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 26 Participation in another clinical study with an investigational product during the last 3 months 27 Previous randomization in the present study 28 Known history or current abuse of drugs or alcohol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of urine-leukotriene E4 (u-LTE4) in CAD patients.;Secondary Objective: To assess the effect of AZD5718 on change from baseline in Coronary Flow Velocity Reserve (CFVR) in CAD patients. To assess the pharmacokinetics (PK) of AZD5718 after repeated oral dosing in CAD patients To assess the effect of AZD5718 on coronary flow parameters To assess the effect of AZD5718 on change in echocardiographic parameters in CAD patients.;Primary end point(s): The primary efficacy variable will test the null hypothesis that patients given AZD5718 200mg have less than 80% inhibition of u-LTE4 compared to placebo, versus the alternative hypothesis that patients given AZD5718 200mg have equal or more than 80% inhibition of u-LTE4 compared to placebo (one-sided 97.5% confidence interval).;Timepoint(s) of evaluation of this end point: Percentage change at Visit 4 from baseline (Visit 2) in creatinine-normalised u-LTE4. Summary statistics per time point the variables are measured will also be presented. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following secondary efficacy variables are all measured as change from baseline: CFVR LAD resting mean diastolic flow velocity LAD hyperaemic flow velocity Measurements of left ventricular (LV) systolic and diastolic function, more specifically LV ejection fraction (LVEF) at rest LV Global Longitudinal Strain (GLS) at rest and at hyperaemia LV Global Circumferential Strain (GCS) at rest and at hyperaemia LV longitudinal early diastolic strain rate Summary statistics per time point the variables are measured will also be presented.;Timepoint(s) of evaluation of this end point: Percentage change at Visit 4 from baseline (Visit 2) in creatinine-normalised u-LTE4. Summary statistics per time point the variables are measured will also be presented. | — |
Countries
Denmark, Finland, Sweden
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed