Trial Outcomes & Findings for AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD). (NCT NCT03317002)
NCT ID: NCT03317002
Last Updated: 2021-06-30
Results Overview
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
129 participants
Primary outcome timeframe
Baseline and 4 weeks
Results posted on
2021-06-30
Participant Flow
The study was conducted in 3 countries at 9 sites; 3 in Denmark, 2 in Finland and 4 in Sweden.
Participants underwent a screening visit between 2 and within 27 days before receiving the first dose of IP.
Participant milestones
| Measure |
AZD5718 (200 mg)
AZD5718 (200 mg)
|
AZD5718 (50 mg)
AZD5718 (50 mg)
|
Placebo
Placebo
|
|---|---|---|---|
|
Overall Study
STARTED
|
52
|
25
|
52
|
|
Overall Study
COMPLETED
|
50
|
24
|
51
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
AZD5718 Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 in Patients With Coronary Artery Disease (CAD).
Baseline characteristics by cohort
| Measure |
AZD5718 (200 mg)
n=52 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=25 Participants
AZD5718 (50 mg)
|
Placebo
n=51 Participants
Placebo
|
Total
n=128 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61.9 Years
STANDARD_DEVIATION 8.21 • n=5 Participants
|
61.4 Years
STANDARD_DEVIATION 8.12 • n=7 Participants
|
61.1 Years
STANDARD_DEVIATION 8.51 • n=5 Participants
|
61.5 Years
STANDARD_DEVIATION 8.26 • n=4 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
111 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
51 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
127 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
52 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
127 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Outcome measures
| Measure |
AZD5718 (200 mg)
n=49 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=24 Participants
AZD5718 (50 mg)
|
Placebo
n=50 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
|
0.04 Ratio
Geometric Coefficient of Variation 92.55
|
0.09 Ratio
Geometric Coefficient of Variation 84.32
|
1.09 Ratio
Geometric Coefficient of Variation 44.38
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
Outcome measures
| Measure |
AZD5718 (200 mg)
n=29 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=18 Participants
AZD5718 (50 mg)
|
Placebo
n=36 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in Creatinine-normalized u-LTE4 at Week 12
|
0.04 Ratio
Geometric Coefficient of Variation 92.55
|
0.09 Ratio
Geometric Coefficient of Variation 84.32
|
1.09 Ratio
Geometric Coefficient of Variation 44.38
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Outcome measures
| Measure |
AZD5718 (200 mg)
n=16 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=11 Participants
AZD5718 (50 mg)
|
Placebo
n=24 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in CFVR at Week 12
|
0.93 Ratio
Geometric Coefficient of Variation 23.64
|
0.98 Ratio
Geometric Coefficient of Variation 39.53
|
1.16 Ratio
Geometric Coefficient of Variation 33.46
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
CFVR = Coronary Flow Velocity Reserve = LAD(hyperaemic)/LAD(rest)
Outcome measures
| Measure |
AZD5718 (200 mg)
n=36 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=16 Participants
AZD5718 (50 mg)
|
Placebo
n=38 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in CFVR at Week 4
|
1.03 Ratio
Geometric Coefficient of Variation 28.34
|
1.15 Ratio
Geometric Coefficient of Variation 31.47
|
1.08 Ratio
Geometric Coefficient of Variation 33.16
|
SECONDARY outcome
Timeframe: 16 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
Outcome measures
| Measure |
AZD5718 (200 mg)
n=52 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=25 Participants
AZD5718 (50 mg)
|
Placebo
Placebo
|
|---|---|---|---|
|
Summary of Plasma Concentrations of AZD5718
Baseline: 1-8 Hours Post-Dose
|
611.88 nmol/L
Geometric Coefficient of Variation 234.50
|
47.88 nmol/L
Geometric Coefficient of Variation 497.86
|
—
|
|
Summary of Plasma Concentrations of AZD5718
2 weeks (Visit 3): 20-28 Hours Post-Dose
|
59.36 nmol/L
Geometric Coefficient of Variation 90.97
|
16.57 nmol/L
Geometric Coefficient of Variation 127.80
|
—
|
|
Summary of Plasma Concentrations of AZD5718
4 weeks (Visit 4): Pre-Dose
|
48.00 nmol/L
Geometric Coefficient of Variation 68.17
|
11.01 nmol/L
Geometric Coefficient of Variation 60.70
|
—
|
|
Summary of Plasma Concentrations of AZD5718
4 weeks (Visit 4): 0-2 Hours Post-Dose
|
339.28 nmol/L
Geometric Coefficient of Variation 243.04
|
38.68 nmol/L
Geometric Coefficient of Variation 159.56
|
—
|
|
Summary of Plasma Concentrations of AZD5718
4 weeks (Visit 4): 2-4 Hours Post-Dose
|
919.22 nmol/L
Geometric Coefficient of Variation 51.26
|
148.64 nmol/L
Geometric Coefficient of Variation 71.86
|
—
|
|
Summary of Plasma Concentrations of AZD5718
4 weeks (Visit 4): 4-8 Hours Post-Dose
|
649.09 nmol/L
Geometric Coefficient of Variation 49.89
|
105.40 nmol/L
Geometric Coefficient of Variation 52.16
|
—
|
|
Summary of Plasma Concentrations of AZD5718
12 weeks (Visit 4c): Pre-Dose
|
65.39 nmol/L
Geometric Coefficient of Variation 91.52
|
13.97 nmol/L
Geometric Coefficient of Variation 88.12
|
—
|
|
Summary of Plasma Concentrations of AZD5718
16 weeks (Visit 5) - FUP 1 month
|
0.51 nmol/L
Geometric Coefficient of Variation 16.39
|
0.50 nmol/L
Geometric Coefficient of Variation 0.00
|
—
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LAD=Left Anterior Descending
Outcome measures
| Measure |
AZD5718 (200 mg)
n=36 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=16 Participants
AZD5718 (50 mg)
|
Placebo
n=38 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LAD Hypereamic Flow at 4 Weeks
|
0.02 m/sec
Standard Deviation 0.16
|
0.04 m/sec
Standard Deviation 0.16
|
0.03 m/sec
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LVEF=Left Ventricular Ejection Fraction
Outcome measures
| Measure |
AZD5718 (200 mg)
n=46 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=22 Participants
AZD5718 (50 mg)
|
Placebo
n=45 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LVEF at 4 Weeks
|
-0.23 percent LVEF
Standard Deviation 5.30
|
2.70 percent LVEF
Standard Deviation 6.39
|
0.48 percent LVEF
Standard Deviation 5.00
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LV=Left Ventricular
Outcome measures
| Measure |
AZD5718 (200 mg)
n=43 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=19 Participants
AZD5718 (50 mg)
|
Placebo
n=44 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks
|
1.02 1/s
Geometric Coefficient of Variation 30.61
|
0.98 1/s
Geometric Coefficient of Variation 33.55
|
1.03 1/s
Geometric Coefficient of Variation 30.45
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LV-GLS = Left Ventricular Global Longitudinal Strain
Outcome measures
| Measure |
AZD5718 (200 mg)
n=43 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=17 Participants
AZD5718 (50 mg)
|
Placebo
n=42 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LV-GLS at Rest at Week 4
|
-0.41 Percent LV-GLS
Standard Deviation 3.00
|
0.34 Percent LV-GLS
Standard Deviation 2.47
|
-0.63 Percent LV-GLS
Standard Deviation 2.61
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LV-GCS = Left Ventricular Global Circumferential Strain
Outcome measures
| Measure |
AZD5718 (200 mg)
n=39 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=16 Participants
AZD5718 (50 mg)
|
Placebo
n=34 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LV-GCS at Rest at Week 4
|
0.34 Percent
Standard Deviation 7.24
|
1.71 Percent
Standard Deviation 5.40
|
-1.88 Percent
Standard Deviation 6.78
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Number of participants analysed differs from participant flow module due to missing data
LAD=Left Anterior Descending
Outcome measures
| Measure |
AZD5718 (200 mg)
n=36 Participants
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=16 Participants
AZD5718 (50 mg)
|
Placebo
n=38 Participants
Placebo
|
|---|---|---|---|
|
Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks
|
1.01 m/sec
Geometric Coefficient of Variation 23.31
|
0.92 m/sec
Geometric Coefficient of Variation 23.68
|
0.99 m/sec
Geometric Coefficient of Variation 20.14
|
Adverse Events
AZD5718 (200 mg)
Serious events: 4 serious events
Other events: 27 other events
Deaths: 0 deaths
AZD5718 (50 mg)
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AZD5718 (200 mg)
n=52 participants at risk
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=25 participants at risk
AZD5718 (50 mg)
|
Placebo
n=51 participants at risk
Placebo
|
|---|---|---|---|
|
Infections and infestations
Post procedural sepsis
|
1.9%
1/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
1.9%
1/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Cardiac disorders
Ventricular fibrillation
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
General disorders
Chest pain
|
3.8%
2/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
Other adverse events
| Measure |
AZD5718 (200 mg)
n=52 participants at risk
AZD5718 (200 mg)
|
AZD5718 (50 mg)
n=25 participants at risk
AZD5718 (50 mg)
|
Placebo
n=51 participants at risk
Placebo
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
11.5%
6/52 • Treatment period, up to 12 weeks
|
16.0%
4/25 • Treatment period, up to 12 weeks
|
13.7%
7/51 • Treatment period, up to 12 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
7.7%
4/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
3.9%
2/51 • Treatment period, up to 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.5%
6/52 • Treatment period, up to 12 weeks
|
16.0%
4/25 • Treatment period, up to 12 weeks
|
13.7%
7/51 • Treatment period, up to 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.6%
5/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
Nervous system disorders
Dizziness
|
9.6%
5/52 • Treatment period, up to 12 weeks
|
8.0%
2/25 • Treatment period, up to 12 weeks
|
7.8%
4/51 • Treatment period, up to 12 weeks
|
|
Nervous system disorders
Headache
|
1.9%
1/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
3.9%
2/51 • Treatment period, up to 12 weeks
|
|
General disorders
Chest pain
|
5.8%
3/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
5.9%
3/51 • Treatment period, up to 12 weeks
|
|
General disorders
Fatigue
|
5.8%
3/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
0.00%
0/51 • Treatment period, up to 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.8%
3/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
Gastrointestinal disorders
Nausea
|
1.9%
1/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
3.9%
2/51 • Treatment period, up to 12 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
3.8%
2/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
7.8%
4/51 • Treatment period, up to 12 weeks
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/52 • Treatment period, up to 12 weeks
|
0.00%
0/25 • Treatment period, up to 12 weeks
|
7.8%
4/51 • Treatment period, up to 12 weeks
|
|
Psychiatric disorders
Anxiety
|
3.8%
2/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
3.8%
2/52 • Treatment period, up to 12 weeks
|
4.0%
1/25 • Treatment period, up to 12 weeks
|
2.0%
1/51 • Treatment period, up to 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER