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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).
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD5718 Dose A | Experimental | AZD5718 Dose A once daily |
|
| AZD5718 Dose B | Experimental | AZD5718 Dose B once daily |
|
| Placebo | Placebo Comparator | Matching placebo once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5718 | Drug | Oral dose of AZD5718 (tablet) |
| |
| AZD5718 |
| 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 |
| 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) |
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Inclusion Criteria:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Aarhus | 8200 | Denmark | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35842004 | Derived | 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. |
| Label | URL |
|---|---|
| redacted Statistical Analysis Plan | View source |
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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.
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.
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.
Participants underwent a screening visit between 2 and within 27 days before receiving the first dose of IP.
The study was conducted in 3 countries at 9 sites; 3 in Denmark, 2 in Finland and 4 in Sweden.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD5718 (200 mg) | AZD5718 (200 mg) |
| FG001 | AZD5718 (50 mg) | AZD5718 (50 mg) |
| FG002 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 11, 2019 | Jun 29, 2021 |
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| Drug |
Oral dose of AZD5718 (tablet) |
|
| Placebo | Drug | Matching placebo (tablet) |
|
| 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 |
| Frederiksberg |
| 2000 |
| Denmark |
| Research Site | Odense C | 5000 | Denmark |
| Research Site | Kuopio | 70210 | Finland |
| Research Site | Turku | 20520 | Finland |
| Research Site | Gothenburg | 413 45 | Sweden |
| Research Site | Lund | 222 42 | Sweden |
| Research Site | Stockholm | 171 76 | Sweden |
| Research Site | Uppsala | 75185 | Sweden |
| redacted Clinical Study Protocol | View source |
| Placebo |
Placebo |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD5718 (200 mg) | AZD5718 (200 mg) |
| BG001 | AZD5718 (50 mg) | AZD5718 (50 mg) |
| BG002 | Placebo | Placebo |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Creatinine-normalized u-LTE4 at Week 4 | Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline and 4 weeks |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Creatinine-normalized u-LTE4 at Week 12 | Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline and 12 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in CFVR at Week 12 | CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest) | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline and 12 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in CFVR at Week 4 | CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest) | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Summary of Plasma Concentrations of AZD5718 | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 16 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LAD Hypereamic Flow at 4 Weeks | LAD=Left Anterior Descending | Number of participants analysed differs from participant flow module due to missing data | Posted | Mean | Standard Deviation | m/sec | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LVEF at 4 Weeks | LVEF=Left Ventricular Ejection Fraction | Number of participants analysed differs from participant flow module due to missing data | Posted | Mean | Standard Deviation | percent LVEF | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks | LV=Left Ventricular | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/s | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LV-GLS at Rest at Week 4 | LV-GLS = Left Ventricular Global Longitudinal Strain | Number of participants analysed differs from participant flow module due to missing data | Posted | Mean | Standard Deviation | Percent LV-GLS | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LV-GCS at Rest at Week 4 | LV-GCS = Left Ventricular Global Circumferential Strain | Number of participants analysed differs from participant flow module due to missing data | Posted | Mean | Standard Deviation | Percent | Baseline and 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks | LAD=Left Anterior Descending | Number of participants analysed differs from participant flow module due to missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | m/sec | Baseline and 4 weeks |
|
|
Treatment period, up to 12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZD5718 (200 mg) | AZD5718 (200 mg) | 0 | 52 | 4 | 52 | 27 | 52 |
| EG001 | AZD5718 (50 mg) | AZD5718 (50 mg) | 0 | 25 | 3 | 25 | 12 | 25 |
| EG002 | Placebo | Placebo | 0 | 51 | 4 | 51 | 22 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post procedural sepsis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca | 1-877-240-9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 18, 2020 | Jun 29, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C000630861 | AZD5718 |
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| Male |
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| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Ratio |
| 0.08 |
| 1-Sided |
| 95 |
| 0.10 |
| Superiority |
|
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