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

Primary Purpose

Coronary Artery Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD5718
AZD5718
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

AZD5718 Dose A

AZD5718 Dose B

Placebo

Arm Description

AZD5718 Dose A once daily

AZD5718 Dose B once daily

Matching placebo once daily

Outcomes

Primary Outcome Measures

Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine

Secondary Outcome Measures

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

Full Information

First Posted
October 5, 2017
Last Updated
June 29, 2021
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT03317002
Brief Title
AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD).
Acronym
FLAVOUR
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 30, 2017 (Actual)
Primary Completion Date
April 8, 2020 (Actual)
Study Completion Date
April 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
129 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD5718 Dose A
Arm Type
Experimental
Arm Description
AZD5718 Dose A once daily
Arm Title
AZD5718 Dose B
Arm Type
Experimental
Arm Description
AZD5718 Dose B once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo once daily
Intervention Type
Drug
Intervention Name(s)
AZD5718
Intervention Description
Oral dose of AZD5718 (tablet)
Intervention Type
Drug
Intervention Name(s)
AZD5718
Intervention Description
Oral dose of AZD5718 (tablet)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo (tablet)
Primary Outcome Measure Information:
Title
Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
Description
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Time Frame
Baseline and 4 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Creatinine-normalized u-LTE4 at Week 12
Description
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Time Frame
Baseline and 12 weeks
Title
Change From Baseline in CFVR at Week 12
Description
CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Time Frame
Baseline and 12 weeks
Title
Change From Baseline in CFVR at Week 4
Description
CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Time Frame
Baseline and 4 weeks
Title
Summary of Plasma Concentrations of AZD5718
Time Frame
16 weeks
Title
Change From Baseline in LAD Hypereamic Flow at 4 Weeks
Description
LAD=Left Anterior Descending
Time Frame
Baseline and 4 weeks
Title
Change From Baseline in LVEF at 4 Weeks
Description
LVEF=Left Ventricular Ejection Fraction
Time Frame
Baseline and 4 weeks
Title
Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks
Description
LV=Left Ventricular
Time Frame
Baseline and 4 weeks
Title
Change From Baseline in LV-GLS at Rest at Week 4
Description
LV-GLS = Left Ventricular Global Longitudinal Strain
Time Frame
Baseline and 4 weeks
Title
Change From Baseline in LV-GCS at Rest at Week 4
Description
LV-GCS = Left Ventricular Global Circumferential Strain
Time Frame
Baseline and 4 weeks
Title
Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks
Description
LAD=Left Anterior Descending
Time Frame
Baseline and 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Research Site
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Research Site
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Facility Name
Research Site
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Research Site
City
Kuopio
ZIP/Postal Code
70210
Country
Finland
Facility Name
Research Site
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Research Site
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Research Site
City
Lund
ZIP/Postal Code
222 42
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Facility Name
Research Site
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Citations:
PubMed Identifier
35842004
Citation
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D7550C00003&amp;attachmentIdentifier=bfc8ef9d-0ec7-4ad9-9153-27fb6e2d880e&amp;fileName=Statistical_Analysis_Plan_redacted.pdf&amp;versionIdentifier=
Description
redacted Statistical Analysis Plan
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D7550C00003&amp;attachmentIdentifier=72c1cf18-0bad-4d45-a0cd-640350986d43&amp;fileName=Clinical_Study_Protocol_redacted.pdf&amp;versionIdentifier=
Description
redacted Clinical Study Protocol

Learn more about this trial

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

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