E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Action Pharma is developing AP214 Acetate for the prevention of postsurgical kidney injury after cardiac surgery.
Trial population is patients with increased risk for development of Kidney Injury after cardiac surgery with extracorporal circulation. |
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E.1.1.1 | Medical condition in easily understood language |
Action Pharma is developing AP214 Acetate to prevent patients undergoing surgey for hearth and central vessel diseases in developing kidney injury/ failure. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056675 |
E.1.2 | Term | Postoperative renal failure |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety
To assess the safety and tolerability of AP214 compared to placebo
Efficacy
To assess the effect of AP214 versus placebo on the maximal postoperative change in absolute values of Serum Creatinine (SCr) compared to baseline within the first 7 days after surgery or until discharge from hospital, whichever comes first.
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E.2.2 | Secondary objectives of the trial |
To assess the ability of AP214 compared to placebo to reduce postoperative changes in GFR, SCr and eGFR compared to baseline.
To assess the proportion of AP214 treated patients compared to placebo developing postoperative acute kidney (AKI) injury according to the RIFLE and AKIN score.
To assess the proportion of patients reaching the composite endpoint of death, need of renal replacement therapy (RRT) or a 25% reduction in renal function when compared to placebo treatment over a 90 day postoperative period.
To compare the ability of the two AP214 dosing regimens to protect against development of post surgical changes in renal function.
- on the maximal postoperative change in absolute values of SCr;
- on post operative changes in GFR and eGFR
- in the proportion of patients developing AKI according to the RIFLE and AKIN score
To compare the ability of the two AP214 dosing regimens to reduce postoperative changes in SCr, eGFR and GFR compared to baseline. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Has signed the trial-specific informed consent form.
2. Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized, e.g. tubal ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
3. Patients undergoing combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery), or
4. Patients undergoing surgery of more than one cardiac valve (valves surgery), or
5. Patients undergoing surgery of the aortic root or ascending part of the aorta, or
6. Patients undergoing surgery of the aortic root or ascending part of the aorta, combined with CABG and/or valve(s) surgery, or
7. Patients with stage III chronic kidney disease (eGFR 30-59 ml/min determined by the Modification of Diet in Renal Disease (MDRD) undergoing CABG or Single Valve surgery
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E.4 | Principal exclusion criteria |
1. Cardiac surgery to be performed “off pump” without cardiopulmonary bypass.
2. Cardiac surgery to be performed with hypothermic circulatory arrest.
3. Confirmed or suspected endocarditis.
4. EF ≤ 20%, evaluated within 2 months prior to screening visit.
5. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
6. Active peptic ulcer disease and gastritis.
7. Receiving dopamine, adrenalin or noradrenalin at any dose at any time 14 days prior to Day of surgery.
8. Known or suspected hypersensitivity to the investigational medicinal product.
9. Current participation in any other interventional clinical trial.
10. Previously dosed with AP214.
11. Use of investigational medicinal products within the previous 6 months.
12. Body weight above 130 kg.
13. History of any organ transplant.
14. Women who are of childbearing potential, pregnant, or breast-feeding.
15. Current abuse of alcohol or substance, according to the investigator’s medical judgment.
16. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures.
17. Any history of cancer within the last 2 years
18. Any history of dialysis.
19. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Efficacy:Changes in sCR within 7 days after surgery;
Safety: Safety Day 0-7 and 0-90.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
- changes in GFR at Day 3 or 4 and eGFR at Day 0-7 compared to baseline
- changes in sCr and eGFR at Days 28, 60 and 90
- proportion of AP214 treated patients compared to placebo developing
postoperative acute kidney injury according to the Rifle score
- proportion of AP214 patients compared to placebo developing postoperative acute
kidney injury according to AKIN criteria
- proportion of AP214 patients reaching the composite endpoint of death, need of
renal replacement therapy or a 25% reduction in renal function when compared to
placebo over the 90 day postoperative period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Please see protocol: Amendment 1, Final version 2.0 |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |