Action Pharma A/S is developing AP214 Acetate for the prevention of postsurgical kidney injury after thoracic aortic aneurysm repair surgery. In phase 2: Patients undergoing cardiac surgery, defined as coronary artery bypass grafting (CABG), valve(s), CABG/valve(s) and/or aortic root or ascending aortic aneurysm repair surgery with higher than average risk for severe acute kidney injury (AKI). MedDRA version: 9.1 Level: LLT Classification code 10056675 Term: Postoperative renal failure
Conditions
Interventions
Product Name: AP214 Acetate
Product Code: AP214
Pharmaceutical Form: Injection*
Current Sponsor code: AP214
Other descriptive name: Synthetic Melanocortin Analogue
Concentration unit: mg/ml milligram(
Sponsors
Action Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has signed the trial specific informed consent form. 2. Patients 18 to 80 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 CABG, valve(s), CABG/valve(s) and/or aortic root or ascending aortic aneurysm repair surgery. 4. Cleveland Clinic Renal Score = 2 (higher than average risk for AKI). 5. EF = 30%, evaluated within 2 months prior to screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Cardiac surgery to be performed “off pump” without cardiopulmonary bypass. 2. Circulatory arrest in connection with aortic root or ascending aortic aneurysm repair surgery. 3. Confirmed or suspected endocarditis. 4. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure. 5. Receiving Aprotinin during the trial, from screening to Day 90. 6. Having undergone cardiovascular catherization = 48 hours prior to scheduled surgery. 7. Active peptic ulcer disease and gastritis. 8. Hemoccult positive stools, hematological, bleeding, and coagulation disorders. 9. Receiving dopamine at renal doses (2-4 mcg/kg/min), from screening to Day of surgery. 10. S-Creatinine greater than 2.1 mg/dl. 11. Known or suspected hypersensitivity to the investigational medicinal product. 12. Known or suspected hypersensitivity to ondansetron or other selective 5- HT3 receptor antagonists 13. Current participation in any other interventional clinical trial. 14. Previously dosed with AP214. 15. Use of investigational medicinal products within the previous 6 months. 16. Body weight above 140 kg. 17. History of any organ transplant. 18. Women who are of childbearing potential, pregnant or breast-feeding. 19. Current abuse of alcohol or substance, according to the investigator’s medical judgement. 20. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures. 21. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pharmacokinetics To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery. Safety To assess the safety and tolerability of AP214, defined as a descriptive analysis of AEs and SAEs (including analysis of severity and relationship to trial drug) from Day 0-90 and divided into the following periods: Day 0-4; Day 5-14, Day 15-28, and Day 29 -90. ;Secondary Objective: Safety To assess the safety and tolerability of AP214 on standard safety laboratory data. To assess the safety and tolerability of AP214 on vital signs. To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality from Day 0-28 and Day 0-90 To assess the effect of AP214 at an organ level and systemically: 1. Central nervous system 2. Heart echocardiography (TTE) prior to surgery. 3. Lung 4. Wound healing Pharmacodynamics: To assess effect of AP214 on cardiac surgery induced systemic inflammation To assess effect of AP214 on development of post-surgical AKI Drug exposure: To determine in patients in cohort 1 the plasma exposure of AP214 following intravenous administration. To explore the impact of AP214 on cardiac surgery induced systemic inflammation To explore the impact of AP214 on the development of post-surgical AKI. ;Primary end point(s): Pharmacokinetics To assess in patients the pharmacokinetics of AP214 administered as three infusions administered over 10 minutes (prior to skin incision, at the time of clamp-release and 6 hours after clamp-release), in patients undergoing cardiac surgery that are at increased risk of AKI. Safety To assess the safety and tolerability of AP214 as three infusions administered over 10 minutes (prior to skin incision, at the time of clamp-release and 6 hours after clamp-release), in patients undergoing cardiac surgery that are at increased risk of AKI defined as a descriptive analysis of AEs and SAEs (including analysis o | — |
Countries
Denmark
Outcome results
None listed