ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19
Study Details
Study Description
Brief Summary
The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
The ARCADIA Trial will assess the safety and efficacy of AZD1656 in 150 patients with either Type 1 or Type 2 diabetes who have been hospitalised with COVID-19.
AZD1656 is a glucokinase (GK; hexokinase 4) activator which has been shown to reduce blood glucose for up to 4 months in humans. Diabetic patients admitted to hospital with COVID-19 often present with hyperglycaemia and are particularly vulnerable to progression to severe COVID-19. Treatment with AZD1656 (in addition to their usual care) may provide additional glucose control which could help improve clinical outcomes in both Type 1 and Type 2 diabetic populations.
In addition to its glucose lowering effect, AZD1656 may have additional benefits to COVID-19 patients via its effects on immune function. In many patients with severe COVID-19, an overreaction of the body's own immune system can cause severe problems including damage to the lungs and heart, which can lead to breathing problems necessitating intubation and ventilation. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017)). AZD1656 could enhance Treg migratory capacity and may prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19, leading to lower requirements for oxygen therapy and assisted ventilation, and reduced incidences of pneumonia and acute respiratory distress syndrome (ARDS).
Diabetic patients hospitalised with COVID-19 will be randomised to receive either AZD1656 tablets or placebo tablets on a 1:1 basis until they are discharged from hospital or until they require intubation/mechanical ventilation. The aim of the study is to determine whether AZD1656 improves clinical outcomes in diabetic patients hospitalised with COVID-19. The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement will be used as the standard methodology for measuring patient outcomes.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: AZD1656 (plus Usual Hospital Care) 50mg film-coated tablets at a dose of 100mg BID |
Drug: AZD1656
50mg film-coated tablets (at daily dose of 100mg BID)
|
Placebo Comparator: Matched Placebo (plus Usual Hospital Care) Matched placebo tablets |
Other: Placebo
Matched placebo tablets
|
Outcome Measures
Primary Outcome Measures
- Clinical Improvement by Day 14 [Day 1 to Day 14]
The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 14 versus baseline, comparing AZD1656 treatment with placebo. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient. Results are presented as number of responders. Patients who were assigned a WHO score of 1, 2 or 3 at Day 14 were considered a treatment responder. A patient who was discharged before Day 14 was also considered a responder. All other patients (WHO scores 4-8 at Day 14) were considered treatment failures.
Secondary Outcome Measures
- Clinical Improvement at Day 7, 14 and 21 [Day 1 to Day 21]
The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo. Results are presented as the percentage of patients categorised at each severity rating at each timepoint on the WHO 8-point OSCI scale. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient. Study Drug Discontinuation was the date on which a patient discontinued treatment. Treatment was given for a maximum of 21 days, or until date of hospital discharge (WHO score 1 or 2), or date mechanical ventilation was required (WHO score 6 or 7) or until date of death (WHO score 8).
- Glycaemic Control [Day 1 to Day 21]
Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo
- Occurrence of Adverse Events [Day 1 to Day 28]
Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo
- Occurrence of Serious Adverse Events [Day 1 to Day 28]
Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo
- Duration of Hospitalisation [Day 1 to Day 21]
Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo
- Mortality Rate [Day 1 to Day 28]
Mortality rate in patients receiving AZD1656 compared with placebo.
- Intubation/Mechanical Ventilation [Day 1 to Day 21]
Number of Patients Receiving Intubation/Mechanical Ventilation
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or Female.
-
Aged 18 and older.
-
Have either Type I or Type II Diabetes Mellitus.
-
Hospitalised with suspected or confirmed novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) infection at time of enrolment, categorised as stage 3, 4 or 5 on the WHO Ordinal Scale for Clinical Improvement.
-
Blood glucose level at or above 4 mmol/L.
-
Able to take oral (tablet) formulation of medication.
-
Patient is able to provide written informed consent prior to initiation of any study procedures.
Exclusion Criteria:
-
In the opinion of the clinical team, progression to intubation or mechanical ventilation is imminent and inevitable, within the next 24 hours, irrespective of the provision of treatments.
-
Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
-
Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
-
Pregnant or breast feeding.
-
Men, and women of child-bearing potential, unwilling to use highly effective contraception during their participation in the trial and for 2 weeks after study completion.
-
Anticipated transfer to another hospital which is not a study site within 72 hours.
-
Known sensitivity to any of the study medication/placebo excipients.
-
Prior dosing with AZD1656 on a previous clinical trial.
-
Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
-
Any known non-COVID-19, non-diabetes related, serious condition which, in the opinion of the clinical team, makes the patient unsuitable for the trial.
-
Known history of drug or alcohol abuse within previous 12 months of screening.
-
Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
-
Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.
-
Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product (IMP) containing small molecule treatment(s) within 30 days or 5 half-lives (whichever is longer) prior to enrolment into this study, or containing biological treatment(s) within 3 months prior to entry into this study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308) | Brno | Czechia | ||
2 | Nemocnice Hořovice (309) | Hořovice | Czechia | ||
3 | Oblastni Nemocnice Kolín (306) | Kolín | Czechia | ||
4 | Klaudianova Nemonice (302) | Mladá Boleslav | Czechia | ||
5 | Fakultni Nemocnice V Motole (303) | Prague | Czechia | ||
6 | Thomayerova Nemonice (310) | Prague | Czechia | ||
7 | Nemocnice Třebíč (305) | Třebíč | Czechia | ||
8 | Colentina Clinical Hospital (204) | Bucharest | Romania | ||
9 | Spitalul Clinic de Boli Infectioase Cluj-Napoca (203) | Cluj-Napoca | Romania | ||
10 | Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca (202) | Cluj-Napoca | Romania | ||
11 | Spitalul Clinic de Boli Infectioase Constanţa (207) | Constanţa | Romania | ||
12 | Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Craiova (206) | Craiova | Romania | ||
13 | Spitalul Judetean de Urgenta Deva (208) | Deva | Romania | ||
14 | Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iaşi (205) | Iaşi | Romania | ||
15 | Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timişoara (201) | Timişoara | Romania | ||
16 | Barnsley Hospital NHS Foundation Trust (105) | Barnsley | United Kingdom | ||
17 | Bolton NHS Foundation Trust (122) | Bolton | United Kingdom | ||
18 | Bradford Teaching Hospitals NHS Foundation Trust (103) | Bradford | United Kingdom | BD9 6RJ | |
19 | North Bristol NHS Trust (116) | Bristol | United Kingdom | BS10 5NB | |
20 | County Durham and Darlington NHS Foundation Trust (121) | Darlington | United Kingdom | ||
21 | The Dudley Group NHS Foundation Trust (107) | Dudley | United Kingdom | DY1 2HQ | |
22 | Medway NHS Foundation Trust (108) | Gillingham | United Kingdom | ME7 5NY | |
23 | Hull & East Yorkshire NHS Trust (102) | Hull | United Kingdom | ||
24 | Barts Health NHS Trust (101 and 111) | London | United Kingdom | E1 1FR | |
25 | Royal Free London NHS Foundation Trust (119) | London | United Kingdom | NW3 2QG | |
26 | St George's University Hospitals NHS Foundation Trust (114) | London | United Kingdom | ||
27 | Penine Acute Hospitals NHS Trust (106) | Salford | United Kingdom | M6 8HD | |
28 | Sheffield Hospitals NHS Foundation Trust (104) | Sheffield | United Kingdom | S10 2SB | |
29 | Somerset NHS Foundation Trust (109) | Taunton | United Kingdom | TA1 5DA | |
30 | Walsall Healthcare NHS Trust (113) | Walsall | United Kingdom | WS2 9PS |
Sponsors and Collaborators
- St George Street Capital
Investigators
- Principal Investigator: Kieran McCafferty, MD, Barts & The London NHS Trust
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- SGS.1656.201
- 2020-002211-21
Study Results
Participant Flow
Recruitment Details | 170 subjects were screened for participation. 13 subjects were screening failures. 156 subjects were randomized of which 3 subjects withdrew consent prior to start of study medication. 153 subjects started with study treatment. |
---|---|
Pre-assignment Detail |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Period Title: Overall Study | ||
STARTED | 80 | 73 |
COMPLETED | 79 | 71 |
NOT COMPLETED | 1 | 2 |
Baseline Characteristics
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) | Total |
---|---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets | Total of all reporting groups |
Overall Participants | 80 | 73 | 153 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
38
47.5%
|
31
42.5%
|
69
45.1%
|
>=65 years |
42
52.5%
|
42
57.5%
|
84
54.9%
|
Sex: Female, Male (Count of Participants) | |||
Female |
30
37.5%
|
26
35.6%
|
56
36.6%
|
Male |
50
62.5%
|
47
64.4%
|
97
63.4%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
77
96.3%
|
70
95.9%
|
147
96.1%
|
Unknown or Not Reported |
3
3.8%
|
3
4.1%
|
6
3.9%
|
Region of Enrollment (Count of Participants) | |||
Romania |
19
23.8%
|
14
19.2%
|
33
21.6%
|
Czechia |
27
33.8%
|
22
30.1%
|
49
32%
|
United Kingdom |
34
42.5%
|
37
50.7%
|
71
46.4%
|
WHO OSCI rating (Count of Participants) | |||
3 - Hospitalised, no oxygen |
19
23.8%
|
13
17.8%
|
32
20.9%
|
4 - Hospitalised, oxygen |
52
65%
|
42
57.5%
|
94
61.4%
|
5 - Non-invasive ventilation or high flow oxygen |
9
11.3%
|
18
24.7%
|
27
17.6%
|
Diabetes Type (Count of Participants) | |||
Type 1 |
1
1.3%
|
2
2.7%
|
3
2%
|
Type 2 |
79
98.8%
|
71
97.3%
|
150
98%
|
Vitamin D group (Count of Participants) | |||
< 25 nmol/l |
31
38.8%
|
27
37%
|
58
37.9%
|
>= 25 nmol/l |
46
57.5%
|
45
61.6%
|
91
59.5%
|
missing |
3
3.8%
|
1
1.4%
|
4
2.6%
|
Outcome Measures
Title | Clinical Improvement by Day 14 |
---|---|
Description | The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 14 versus baseline, comparing AZD1656 treatment with placebo. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient. Results are presented as number of responders. Patients who were assigned a WHO score of 1, 2 or 3 at Day 14 were considered a treatment responder. A patient who was discharged before Day 14 was also considered a responder. All other patients (WHO scores 4-8 at Day 14) were considered treatment failures. |
Time Frame | Day 1 to Day 14 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participants who received at least one dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Treatment responder |
61
76.3%
|
51
69.9%
|
Treatment failure |
18
22.5%
|
21
28.8%
|
Missing |
1
1.3%
|
1
1.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1854 |
Comments | ||
Method | Chi-squared | |
Comments | Chi-squared test on the one-sided significance level of 2.5% | |
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 1.09 | |
Confidence Interval |
(2-Sided) 95% 0.9 to 1.32 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Clinical Improvement at Day 7, 14 and 21 |
---|---|
Description | The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo. Results are presented as the percentage of patients categorised at each severity rating at each timepoint on the WHO 8-point OSCI scale. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient. Study Drug Discontinuation was the date on which a patient discontinued treatment. Treatment was given for a maximum of 21 days, or until date of hospital discharge (WHO score 1 or 2), or date mechanical ventilation was required (WHO score 6 or 7) or until date of death (WHO score 8). |
Time Frame | Day 1 to Day 21 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participants who received at least one dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Score 1: Ambulatory - no limitation of activities |
0
0%
|
0
0%
|
Score 2: Ambulatory - limitation of activities |
0
0%
|
0
0%
|
Score 3: Hospitalized, no oxygen therapy |
19
23.8%
|
13
17.8%
|
Score 4: Hospitalized, oxygen by mask or nasal prongs |
52
65%
|
42
57.5%
|
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen |
9
11.3%
|
18
24.7%
|
Score 6: Hospitalized, intubation or mechanical ventilation |
0
0%
|
0
0%
|
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO |
0
0%
|
0
0%
|
Score 8: Death |
0
0%
|
0
0%
|
Missing |
0
0%
|
0
0%
|
Score 1: Ambulatory - no limitation of activities |
7
8.8%
|
7
9.6%
|
Score 2: Ambulatory - limitation of activities |
22
27.5%
|
10
13.7%
|
Score 3: Hospitalized, no oxygen therapy |
15
18.8%
|
17
23.3%
|
Score 4: Hospitalized, oxygen by mask or nasal prongs |
23
28.8%
|
26
35.6%
|
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen |
10
12.5%
|
5
6.8%
|
Score 6: Hospitalized, intubation or mechanical ventilation |
2
2.5%
|
3
4.1%
|
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO |
0
0%
|
0
0%
|
Score 8: Death |
0
0%
|
5
6.8%
|
Missing |
1
1.3%
|
0
0%
|
Score 1: Ambulatory - no limitation of activities |
16
20%
|
14
19.2%
|
Score 2: Ambulatory - limitation of activities |
37
46.3%
|
30
41.1%
|
Score 3: Hospitalized, no oxygen therapy |
8
10%
|
7
9.6%
|
Score 4: Hospitalized, oxygen by mask or nasal prongs |
9
11.3%
|
10
13.7%
|
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen |
4
5%
|
2
2.7%
|
Score 6: Hospitalized, intubation or mechanical ventilation |
4
5%
|
3
4.1%
|
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO |
0
0%
|
0
0%
|
Score 8: Death |
1
1.3%
|
6
8.2%
|
Missing |
1
1.3%
|
1
1.4%
|
Score 1: Ambulatory - no limitation of activities |
20
25%
|
15
20.5%
|
Score 2: Ambulatory - limitation of activities |
44
55%
|
41
56.2%
|
Score 3: Hospitalized, no oxygen therapy |
4
5%
|
0
0%
|
Score 4: Hospitalized, oxygen by mask or nasal prongs |
2
2.5%
|
5
6.8%
|
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen |
4
5%
|
2
2.7%
|
Score 6: Hospitalized, intubation or mechanical ventilation |
4
5%
|
3
4.1%
|
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO |
0
0%
|
0
0%
|
Score 8: Death |
1
1.3%
|
6
8.2%
|
Missing |
1
1.3%
|
1
1.4%
|
Score 1: Ambulatory - no limitation of activities |
20
25%
|
15
20.5%
|
Score 2: Ambulatory - limitation of activities |
44
55%
|
40
54.8%
|
Score 3: Hospitalized, no oxygen therapy |
3
3.8%
|
0
0%
|
Score 4: Hospitalized, oxygen by mask or nasal prongs |
3
3.8%
|
5
6.8%
|
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen |
4
5%
|
1
1.4%
|
Score 6: Hospitalized, intubation or mechanical ventilation |
4
5%
|
3
4.1%
|
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO |
0
0%
|
0
0%
|
Score 8: Death |
1
1.3%
|
6
8.2%
|
Missing |
1
1.3%
|
3
4.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0286 |
Comments | Baseline p-value | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | one-side significance level of 2.5% |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0786 |
Comments | Day 7 p-value | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | one-side significance level of 2.5% |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2169 |
Comments | Day 14 p-value | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | one-side significance level of 2.5% |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1860 |
Comments | Day 21 p-value | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | one-sided significance level of 2.5% |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2256 |
Comments | Study Drug Discontinuation (SDD) p-value | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | one-sided significance level of 2.5% |
Title | Glycaemic Control |
---|---|
Description | Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo |
Time Frame | Day 1 to Day 21 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participants who at least received one dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
True |
12
15%
|
13
17.8%
|
False |
68
85%
|
60
82.2%
|
True |
61
76.3%
|
58
79.5%
|
False |
19
23.8%
|
15
20.5%
|
True |
25
31.3%
|
21
28.8%
|
False |
55
68.8%
|
52
71.2%
|
True |
74
92.5%
|
67
91.8%
|
False |
6
7.5%
|
6
8.2%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4006 |
Comments | Increase in Diabetic Medication needed equal or more than 3 days | |
Method | Fisher Exact | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7482 |
Comments | Diabetic Medication is stable/reduced equal or more than 3 days | |
Method | Fisher Exact | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.6949 |
Comments | Increase in Diabetic Medication needed at any time during the study | |
Method | Fisher Exact | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5521 |
Comments | Diabetic Medication is stable/reduced at any time during the study | |
Method | Fisher Exact | |
Comments |
Title | Occurrence of Adverse Events |
---|---|
Description | Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo |
Time Frame | Day 1 to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
This analysis includes all participants who received at least one dose of treatment and had at least one post-baseline safety assessment (where the statement that a patient had no AE on the AE eCRF constitutes a safety assessment). 4 patients from the placebo arm are moved to the AZD1656 arm due to having drug in their PK samples. The assignment of patients to the treatment groups are as actually treated. |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 84 | 69 |
TEAEs leading to study drug discontinuation |
2
|
2
|
Other TEAEs |
28
|
21
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5875 |
Comments | ||
Method | Fisher Exact | |
Comments |
Title | Occurrence of Serious Adverse Events |
---|---|
Description | Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo |
Time Frame | Day 1 to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
This analysis includes all patients who received at least one dose of IMP and had at least one post-baseline safety assessment (where the statement that a patient had no AE on the AE eCRF constitutes a safety assessment). 4 patients from the placebo arm are moved to the AZD1656 arm due to having drug in their PK samples. The assignment of patients to the treatment groups are as actually treated. |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 84 | 69 |
Serious Adverse Events |
4
|
7
|
Other AEs |
28
|
17
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1129 |
Comments | ||
Method | Fisher Exact | |
Comments |
Title | Duration of Hospitalisation |
---|---|
Description | Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo |
Time Frame | Day 1 to Day 21 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participant who at least received on dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Median (95% Confidence Interval) [hours] |
264.3
|
288.7
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1556 |
Comments | ||
Method | Log Rank | |
Comments |
Title | Mortality Rate |
---|---|
Description | Mortality rate in patients receiving AZD1656 compared with placebo. |
Time Frame | Day 1 to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Died |
4
5%
|
9
12.3%
|
Did not die |
75
93.8%
|
63
86.3%
|
Missing |
1
1.3%
|
1
1.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0903 |
Comments | ||
Method | Fisher Exact | |
Comments | The p-value is assessed by means of an Fisher's exact test on the one-sided significance level of 2.5% | |
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 0.41 | |
Confidence Interval |
(2-Sided) 95% 0.13 to 1.26 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Intubation/Mechanical Ventilation |
---|---|
Description | Number of Patients Receiving Intubation/Mechanical Ventilation |
Time Frame | Day 1 to Day 21 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participants who at least received one dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Receiving Intubation/Mechanical Ventilation |
3
3.8%
|
3
4.1%
|
Not Receiving Intubation/Mechanical Ventilation |
76
95%
|
69
94.5%
|
Missing |
1
1.3%
|
1
1.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.6144 |
Comments | ||
Method | Fisher Exact | |
Comments | One-sided significance level of 2.5% |
Title | Mortality Rate |
---|---|
Description | Mortality rate from randomization up to and including 168 hours post randomization |
Time Frame | Randomization to 168 hours post randomization |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participant who received at least one dose of treatment; patients who withdrew consent are categorised as missing |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Died |
0
0%
|
6
8.2%
|
Did not die |
79
98.8%
|
66
90.4%
|
Missing |
1
1.3%
|
1
1.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0105 |
Comments | ||
Method | Fisher Exact | |
Comments | one-sided significance level of 2.5% |
Title | Proportion of Patients Discharged up to and Including 168 Hours Having a WHO OSCI Rating of 1 or 2 |
---|---|
Description | Proportion of Patients Being Discharged From Hospital up to and Including 168 hrs Having WHO OSCI Rating of 1 or 2 |
Time Frame | Day 1 up to and including 168 hours post randomization |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all participants who had at least one dose of treatment |
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets |
Measure Participants | 80 | 73 |
Discharged from hospital (within 168 hrs with WHO 1 or 2) |
30
37.5%
|
18
24.7%
|
Not discharged from Hospital (within 168 hrs with WHO 1 or 2) |
49
61.3%
|
54
74%
|
Missing |
1
1.3%
|
1
1.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.062 |
Comments | ||
Method | Fisher Exact | |
Comments | one-sided significance level of 2.5% |
Adverse Events
Time Frame | All AEs, including SAEs, were captured after signing the informed consent and until 7 days after treatment discontinuation (up to a maximum of 28 days). | |||
---|---|---|---|---|
Adverse Event Reporting Description | Serious and other Adverse Events were assessed using the Safety Set (SAF) dataset. The SAF dataset included 84 patients in the AZD1656 arm and 69 patients in the placebo arm, All-Cause Mortality was assessed using the Full Analysis Set (FAS) dataset. The FAS dataset included 80 patients in the AZD1656 arm and 73 patients in the placebo arm. | |||
Arm/Group Title | AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) | ||
Arm/Group Description | 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) | Matched placebo tablets Placebo: Matched placebo tablets | ||
All Cause Mortality |
||||
AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/80 (5%) | 9/73 (12.3%) | ||
Serious Adverse Events |
||||
AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/84 (11.9%) | 19/69 (27.5%) | ||
Cardiac disorders | ||||
Angina unstable | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Cardio-respiratory arrest | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Cardiogenic shock | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Myocardial infarction | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Ventricular tachycardia | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Gastrointestinal disorders | ||||
Pancreatitis acute | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Hepatobiliary disorders | ||||
Acute hepatic failure | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Infections and infestations | ||||
Abcess limb | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Gastroenteritis | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Pneumonia bacterial | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Septic shock | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
COVID-19 | 2/84 (2.4%) | 2 | 5/69 (7.2%) | 5 |
COVID-19 pneumonia | 2/84 (2.4%) | 2 | 2/69 (2.9%) | 2 |
Sepsis | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Injury, poisoning and procedural complications | ||||
Fall | 0/84 (0%) | 0 | 2/69 (2.9%) | 2 |
Metabolism and nutrition disorders | ||||
Dehydration | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Hypophagia | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Psychiatric disorders | ||||
Suicide attempt | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Vascular disorders | ||||
Circulatory collapse | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
AZD1656 (Plus Usual Hospital Care) | Matched Placebo (Plus Usual Hospital Care) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 43/84 (51.2%) | 17/69 (24.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 0/84 (0%) | 0 | 2/69 (2.9%) | 2 |
Leucocytosis | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Neutrophilia | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Thrombocytopenia | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Cardiac disorders | ||||
Atrial fibrillation | 2/84 (2.4%) | 2 | 0/69 (0%) | 0 |
Atrial flutter | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Ear and labyrinth disorders | ||||
Ear pain | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Gastrointestinal disorders | ||||
Diarrhoea | 2/84 (2.4%) | 2 | 0/69 (0%) | 0 |
Abdominal tenderness | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Constipation | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Hepatobiliary disorders | ||||
Hepatitis toxic | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Infections and infestations | ||||
Oral candidiasis | 1/84 (1.2%) | 1 | 1/69 (1.4%) | 1 |
Sepsis | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Cystitis | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Device related infection | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Oral fungal infection | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Upper respiratory tract infection | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Urinary tract infection | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Vulvovaginal mycotic infection | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Investigations | ||||
Aspartate aminotransferase increased | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Blood glucose decreased | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Gamma-glutamyltransferase increased | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Vitamin D decreased | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Metabolism and nutrition disorders | ||||
Hypoglycaemia | 8/84 (9.5%) | 13 | 1/69 (1.4%) | 1 |
Hyperglycaemia | 4/84 (4.8%) | 4 | 1/69 (1.4%) | 1 |
Hypokalaemia | 4/84 (4.8%) | 4 | 0/69 (0%) | 0 |
Hyperkalaemia | 2/84 (2.4%) | 2 | 0/69 (0%) | 0 |
Nervous system disorders | ||||
Reversible ischaemic neurological deficit | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Psychiatric disorders | ||||
Restlessness | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Renal and urinary disorders | ||||
Acute kidney injury | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Dysuria | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Urinary retention | 1/84 (1.2%) | 1 | 0/69 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Pulmonary embolism | 4/84 (4.8%) | 4 | 3/69 (4.3%) | 3 |
Hiccups | 0/84 (0%) | 0 | 1/69 (1.4%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Mike Johnson, Managing Director |
---|---|
Organization | St George Street Capital |
Phone | +447768335460 |
mike@sgscapital.org |
- SGS.1656.201
- 2020-002211-21