Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Cardiac Surgery Clinical Trial

Official title:

Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00903604
• Other study ID #: AP214-CS005
• Status: Completed
• Phase: Phase 2
• First received: May 15, 2009
• Last updated: May 16, 2011
• Start date: May 2009
• Est. completion date: June 2010

Study information

• Verified date: May 2011
• Source: Action Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the present research study is to investigate the pharmacokinetics, as well as safety, tolerability and pharmacodynamics of different ascending dosing regimens of AP214 in patients undergoing cardiac surgery. AP214, the investigational drug, is being developed to potentially prevent post-surgical kidney injury after thoracic aortic aneurysm repair.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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.

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 catheterization = 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-hydroxytryptamine 3 (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 judgment.

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Aortic Aneurysm
• Aortic Root or Ascending Aortic Aneurysm Repair Surgery
• Cardiac Surgery
• Coronary Artery Bypass Grafting
• Valve Surgery

Intervention

Drug:
• AP214
Three 10-minutes infusions of sequential ascending dosages of AP214
• Placebo
Three 10-minutes infusions of isotonic saline solution

Locations

Country	Name	City	State
Denmark	Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Action Pharma A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery.		Day 0 to Day 1	No
Primary	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)		Day 0-90	No
Secondary	To assess effect of AP214 on cardiac surgery induced systemic inflammation o determined by the post-operative peak plasma concentrations of TNF-a, IL-6, IL-8, and IL-10, and area under the curve (AUC) for TNF-a, IL-6, IL-8, and IL-10		0-24 hours	No
Secondary	To assess effect of AP214 on development of post-surgical acute kidney injury (AKI), where AKI is evaluated by evaluation of serum creatinine values, urine output and renal replacement therapy free days.		Day 0 - Day 30	No
Secondary	To assess the safety and tolerability of AP214 on standard safety laboratory data		Day 0-14	No
Secondary	To assess the safety and tolerability of AP214 on vital signs		Day 0-90	No
Secondary	To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality		Day 0-90	No
Secondary	To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically.		Day 0-90	No