E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084382 |
E.1.2 | Term | Coronavirus disease 2019 |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effect of AZD1656 on the cardiorespiratory complications of COVID-19 in hospitalised diabetic patients with known or suspected COVID-19 disease, as measured using the WHO 8-point Ordinal Scale for Clinical Improvement compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are:
• To assess the extent to which AZD1656 supports maintenance of adequate glycaemic control in hospitalised diabetic patients with known or suspected COVID-19.
• To assess the safety and tolerability of AZD1656 in the management of diabetes in hospitalised diabetic patients with known or suspected COVID-19.
• To determine whether AZD1656 affects duration of hospital stay, requirement for mechanical ventilation or mortality in diabetic patients with known or suspected COVID-19. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or Female.
2. Aged 18 and older.
3. Have either T1DM or T2DM.
4. 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.
5. Blood glucose level at or above 4 mmol/L.
6. Able to take oral (tablet) formulation of medication.
7. Patient is able to provide written informed consent prior to initiation of any study procedures. |
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E.4 | Principal exclusion criteria |
1. 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.
2. Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
3. Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
4. Pregnant or breast feeding.
5. 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.
6. Anticipated transfer to another hospital which is not a study site within 72 hours.
7. Known sensitivity to any of the study medication/placebo excipients.
8. Prior dosing with AZD1656 on a previous clinical trial.
9. Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
10. 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.
11. Known history of drug or alcohol abuse within previous 12 months of screening.
12. Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
13. Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.
14. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Improvement measured as the percentage of subjects at Day 14 who are in categories 1-3 according to the World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement, comparing AZD1656 treatment to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to protocol for details. |
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E.5.2 | Secondary end point(s) |
• Clinical Improvement measured as the percentage of patients categorised at each severity rating on the WHO 8-point Ordinal Scale at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.
• 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.
• Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo.
• Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo.
• Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo.
• Time from hospital admission to receiving intubation/mechanical ventilation in patients receiving AZD1656 compared with placebo.
• Mortality Rate in patients receiving AZD1656 compared with placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to protocol for details. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |