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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03317002
Recruitment Status : Completed
First Posted : October 23, 2017
Results First Posted : June 30, 2021
Last Update Posted : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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).

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: AZD5718 Drug: Placebo Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 30, 2017
Actual Primary Completion Date : April 8, 2020
Actual Study Completion Date : April 8, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)

Placebo Comparator: Placebo
Matching placebo once daily
Drug: Placebo
Matching placebo (tablet)




Primary Outcome Measures :
  1. Change From Baseline in Creatinine-normalized u-LTE4 at Week 4 [ Time Frame: Baseline and 4 weeks ]
    Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine


Secondary Outcome Measures :
  1. Change From Baseline in Creatinine-normalized u-LTE4 at Week 12 [ Time Frame: Baseline and 12 weeks ]
    Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine

  2. Change From Baseline in CFVR at Week 12 [ Time Frame: Baseline and 12 weeks ]
    CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)

  3. Change From Baseline in CFVR at Week 4 [ Time Frame: Baseline and 4 weeks ]
    CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)

  4. Summary of Plasma Concentrations of AZD5718 [ Time Frame: 16 weeks ]
  5. Change From Baseline in LAD Hypereamic Flow at 4 Weeks [ Time Frame: Baseline and 4 weeks ]
    LAD=Left Anterior Descending

  6. Change From Baseline in LVEF at 4 Weeks [ Time Frame: Baseline and 4 weeks ]
    LVEF=Left Ventricular Ejection Fraction

  7. Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks [ Time Frame: Baseline and 4 weeks ]
    LV=Left Ventricular

  8. Change From Baseline in LV-GLS at Rest at Week 4 [ Time Frame: Baseline and 4 weeks ]
    LV-GLS = Left Ventricular Global Longitudinal Strain

  9. Change From Baseline in LV-GCS at Rest at Week 4 [ Time Frame: Baseline and 4 weeks ]
    LV-GCS = Left Ventricular Global Circumferential Strain

  10. Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks [ Time Frame: Baseline and 4 weeks ]
    LAD=Left Anterior Descending



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03317002


Locations
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Denmark
Research Site
Aarhus, Denmark, 8200
Research Site
Frederiksberg, Denmark, 2000
Research Site
Odense C, Denmark, 5000
Finland
Research Site
Kuopio, Finland, 70210
Research Site
Turku, Finland, 20520
Sweden
Research Site
Göteborg, Sweden, 413 45
Research Site
Lund, Sweden, 222 42
Research Site
Stockholm, Sweden, 171 76
Research Site
Uppsala, Sweden, 75185
Sponsors and Collaborators
AstraZeneca
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] February 11, 2019
Statistical Analysis Plan  [PDF] May 18, 2020

Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03317002    
Other Study ID Numbers: D7550C00003
First Posted: October 23, 2017    Key Record Dates
Results First Posted: June 30, 2021
Last Update Posted: June 30, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases