Clinical Trials Register

Summary
EudraCT Number:	2017-001582-25
Sponsor's Protocol Code Number:	D7550C00003
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2017-001582-25

A.3

Full title of the trial

A 4-week, randomized, single-blind, placebo-controlled, multi-centre, parallel group, phase IIa study to evaluate efficacy, safety and tolerability of oral AZD5718 in patients with coronary artery disease (CAD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

FLAVOUR

A.4.1

Sponsor's protocol code number

D7550C00003

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Information Centre
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AZD5718 100mg Film-coated Tablet
D.3.2	Product code	AZD5718
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	AZD5718
D.3.9.3	Other descriptive name	NA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AZD5718 50mg Film-coated Tablet
D.3.2	Product code	AZD5718
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	AZD5718
D.3.9.3	Other descriptive name	NA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Coronary artery disease

E.1.1.1

Medical condition in easily understood language

Coronary artery disease

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of urine-leukotriene E4 (u-LTE4) in CAD patients.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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 <50% and TIMI flow is ≥ 2
5. Provision of signed and dated, written informed consent prior to any study specific procedures

E.4

Principal 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

E.5 End points

E.5.1

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).

E.5.1.1

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.

E.5.2

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.

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-04-08

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