Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery - Full Text View

Sponsored by:	Action Pharma A/S
Information provided by:	Action Pharma A/S
ClinicalTrials.gov Identifier:	NCT00903604

Purpose

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.

Condition	Intervention	Phase
Cardiac Surgery Coronary Artery Bypass Grafting Valve Surgery Aortic Root or Ascending Aortic Aneurysm Repair Surgery	Drug: AP214 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Resource links provided by NLM:

MedlinePlus related topics: Aneurysms Aortic Aneurysm Coronary Artery Bypass Surgery Heart Surgery Surgery

U.S. FDA Resources

Further study details as provided by Action Pharma A/S:

Primary Outcome Measures:

To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery. [ Time Frame: Day 0 to Day 1 ] [ Designated as safety issue: No ]
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) [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess effect of AP214 on cardiac surgery induced systemic inflammation o determined by the post-operative peak plasma concentrations of TNF-α, IL-6, IL-8, and IL-10, and area under the curve (AUC) for TNF-α, IL-6, IL-8, and IL-10 [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
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. [ Time Frame: Day 0 - Day 30 ] [ Designated as safety issue: No ]
To assess the safety and tolerability of AP214 on standard safety laboratory data [ Time Frame: Day 0-14 ] [ Designated as safety issue: No ]
To assess the safety and tolerability of AP214 on vital signs [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]
To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]
To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically. [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	May 2009
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
AP214: Experimental Infusions of sequential ascending dosages of AP214	Drug: AP214 Three 10-minutes infusions of sequential ascending dosages of AP214
Placebo: Placebo Comparator Infusions of saline solution	Drug: Placebo Three 10-minutes infusions of isotonic saline solution

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Has signed the trial-specific informed consent form.
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.
Patients undergoing CABG, valve(s), CABG/valve(s) and/or aortic root or ascending aortic aneurysm repair surgery.
Cleveland Clinic Renal Score ≥ 2 (higher than average risk for AKI).
EF ≥ 30%, evaluated within 2 months prior to screening visit.

Exclusion Criteria:

Cardiac surgery to be performed "off pump" without cardiopulmonary bypass.
Circulatory arrest in connection with aortic root or ascending aortic aneurysm repair surgery.
Confirmed or suspected endocarditis.
Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
Receiving Aprotinin during the trial, from Screening to Day 90.
Having undergone cardiovascular catheterization ≤ 48 hours prior to scheduled surgery.
Active peptic ulcer disease and gastritis.
Hemoccult positive stools, hematological, bleeding, and coagulation disorders.
Receiving dopamine at renal doses (2-4 mcg/kg/min), from Screening to Day of surgery.
S-Creatinine greater than 2.1 mg/dl.
Known or suspected hypersensitivity to the investigational medicinal product.
Known or suspected hypersensitivity to Ondansetron or other selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
Current participation in any other interventional clinical trial.
Previously dosed with AP214.
Use of investigational medicinal products within the previous 6 months.
Body weight above 140 kg.
History of any organ transplant.
Women who are of childbearing potential, pregnant, or breast-feeding.
Current abuse of alcohol or substance, according to the investigator's medical judgment.
Has a mental incapacity or language barriers precluding adequate understanding of trial procedures.
Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903604

Locations

Denmark
Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet	Recruiting
Copenhagen, Denmark, 2100
Contact: Daniel Steinbrüchel, Professor (+45) 35 45 23 08 daniel.steinbruchel@rh.regionh.dk
Contact: Thomas N Lilleoer, Nurse (+45) 35 45 86 81 thomas.nikolaj.lilleoer@rh.regionh.dk
Principal Investigator: Daniel Steinbrüchel, Professor

Sponsors and Collaborators

Action Pharma A/S

Investigators

Principal Investigator:

Daniel Steinbrüchel, Professor

Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet

More Information

No publications provided

Responsible Party:	Action Pharma A/S ( Action Pharma A/S )
Study ID Numbers:	AP214-CS005
Study First Received:	May 15, 2009
Last Updated:	May 29, 2009
ClinicalTrials.gov Identifier:	NCT00903604 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Action Pharma A/S:

Cardiac surgery
coronary artery bypass grafting
valve surgery
aortic root or ascending aortic aneurysm repair surgery
Acute kidney injury

Study placed in the following topic categories:

Aortic Diseases
Aneurysm
Vascular Diseases
Aortic Aneurysm

Additional relevant MeSH terms:

Aortic Diseases
Aneurysm
Vascular Diseases
Cardiovascular Diseases
Aortic Aneurysm

ClinicalTrials.gov processed this record on September 10, 2009