AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD). (FLAVOUR)

A 12-week, Randomized, Single-blind, Placebo-controlled, Multi-centre, Parallel Group, Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 After 4 and 12-weeks of Treatment in Patients With Coronary Artery Disease (CAD)

This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries. Approximately 138 CAD patients will be randomized to AZD5718 or placebo (treatment duration 12 weeks).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: AZD5718; Drug: Placebo

Detailed Description

This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries (Denmark, Finland and Sweden).

Patients suitable for the study will be identified and screened for eligibility after being hospitalized for Acute Coronary Syndrome (ACS) (Visit 1) comprising ST Elevation Myocardial Infarction (STEMI) or Non-ST Elevation Myocardial Infarction (non-STEMI). At Visit 1, after signing informed consent, study measurements will take place at days 1, 2, 3 and 5 post ACS, where feasible. It is planned that approximately 138 CAD patients will be randomized to ensure at least 66 evaluable patients receiving AZD5718 Dose B or placebo are included with 12 weeks treatment. For supporting dose selection in future studies, a treatment arm with 28 randomized patients receiving AZD5718 Dose A is included in the study. The study was originally designed to be a 4-week study and was amended to be a 12-week study. Therefore, the total number of patients is greater than required for a 12 weeks study (about 100), since some patients will only have 4 weeks of treatment.

An evaluable patient is defined as a patient with a valid Coronary Flow Velocity Reserve (CFVR) measurement at Visit 2 and one post baseline visit as judged by the CFVR Core lab.

On Day 1 (Visit 2), 7 to 28 days after the ACS event, patients willing to participate in the study will complete the screening procedure and, if eligible, be randomized. Treatment duration will be 12 weeks. During the treatment phase, patients will come in to the clinic for study measurements at 2 weeks (visit 3), 4 weeks (visit 4), 8 weeks (visit 4b) and 12 weeks (visit 4c).

A follow-up visit (Visit 5) will be performed at 4 weeks (±4 days) after last dose in order to ensure safety and well-being of the patients

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Research Site
  • Frederiksberg, Denmark, 2000
    • Research Site
  • Odense C, Denmark, 5000
    • Research Site
• Finland
  • Kuopio, Finland, 70210
    • Research Site
  • Turku, Finland, 20520
    • Research Site
• Sweden
  • Göteborg, Sweden, 413 45
    • Research Site
  • Lund, Sweden, 222 42
    • Research Site
  • Stockholm, Sweden, 171 76
    • Research Site
  • Uppsala, Sweden, 75185
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 [troponin] and angiogram) Provision of signed and dated, written informed consent prior to any study specific procedures

Exclusion Criteria:

• 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
• 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 Atrioventricular blockage degree 2-3
• Prior coronary artery by-pass graft (Coronary artery bypass grafting) to Left Anterior Descending artery (LAD)
• Left ventricle ejection fraction < 30%
• Unacceptable level of angina despite maximal medical therapy or unstable angina at entry
• Canadian Cardiovascular Society (CCS) ≥ 3 (Visit 1 or Visit 2)
• Stroke within the previous 6 months from ACS or ongoing treatment with Persantin or Asasantin
• Chronic use of anticoagulants on therapeutic dose (not including thrombosis prophylaxis) during the study
• Planned additional cardiac intervention (e.g., Percutaneous coronary intervention (PCI), Coronary artery bypass grafting (CABG) within next 6 months
• New York Heart Association (NYHA) class III-IV heart failure or decompensated heart failure at discharge or hospitalization for exacerbation of chronic heart failure within the previous 3 months from ACS
• Previously known severe renal disease (Chronic Kidney Disease (CKD) stage 4 or 5) or previously known creatinine clearance calculated by Cockcroft Gault equation <30 ml/min*m2
• Known allergy to adenosine and mannitol, or experience of previous adverse effects of adenosine stress testing.
• Participation in another interventional clinical study with an investigational pharmaceutical product during the last 3 months also including drug eluting stents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Matching placebo once daily	Drug: Placebo; Matching placebo (tablet)
EXPERIMENTAL: AZD5718 Dose A; AZD5718 Dose A once daily	Drug: AZD5718; Oral dose of AZD5718 (tablet)
EXPERIMENTAL: AZD5718 Dose B; AZD5718 Dose B once daily	Drug: AZD5718; Oral dose of AZD5718 (tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Creatinine-normalized u-LTE4 at Week 4	Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Creatinine-normalized u-LTE4 at Week 12	Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine	Baseline and 12 weeks
Change From Baseline in CFVR at Week 12	CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)	Baseline and 12 weeks
Change From Baseline in CFVR at Week 4	CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)	Baseline and 4 weeks
Summary of Plasma Concentrations of AZD5718		16 weeks
Change From Baseline in LAD Hypereamic Flow at 4 Weeks	LAD=Left Anterior Descending	Baseline and 4 weeks
Change From Baseline in LVEF at 4 Weeks	LVEF=Left Ventricular Ejection Fraction	Baseline and 4 weeks
Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks	LV=Left Ventricular	Baseline and 4 weeks
Change From Baseline in LV-GLS at Rest at Week 4	LV-GLS = Left Ventricular Global Longitudinal Strain	Baseline and 4 weeks
Change From Baseline in LV-GCS at Rest at Week 4	LV-GCS = Left Ventricular Global Circumferential Strain	Baseline and 4 weeks
Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks	LAD=Left Anterior Descending	Baseline and 4 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Prescott E, Angeras O, Erlinge D, Grove EL, Hedman M, Jensen LO, Pernow J, Saraste A, Akerblom A, Svedlund S, Rudvik A, Knochel J, Lindstedt EL, Garkaviy P, Gan LM, Gabrielsen A. Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study. Int J Cardiol. 2022 Oct 15;365:34-40. doi: 10.1016/j.ijcard.2022.07.016. Epub 2022 Jul 14.

Helpful Links

• redacted Statistical Analysis Plan
• redacted Clinical Study Protocol

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 30, 2017
• Primary Completion (ACTUAL): April 8, 2020
• Study Completion (ACTUAL): April 8, 2020

Study Registration Dates

• First Submitted: October 5, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (ACTUAL): October 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: D7550C00003

Plan for Individual participant data (IPD)

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

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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