Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

NCT00903604 | Completed Phase 2 DMC

• 1 other identifier: AP214-CS005
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery.

  Day 0 to Day 1

• 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

Secondary Outcomes (6)

• 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

  0-24 hours

• 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

• To assess the safety and tolerability of AP214 on standard safety laboratory data

  Day 0-14

• To assess the safety and tolerability of AP214 on vital signs

  Day 0-90

• To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality

  Day 0-90

Study Arms (2)

AP214

EXPERIMENTAL

Infusions of sequential ascending dosages of AP214

Drug: AP214

Placebo

PLACEBO COMPARATOR

Infusions of saline solution

Drug: Placebo

Interventions

AP214 DRUG

Three 10-minutes infusions of sequential ascending dosages of AP214

AP214

Placebo DRUG

Three 10-minutes infusions of isotonic saline solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Action Pharma A/S: lead

Study Sites (2)

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

Copenhagen, 2100, Denmark

Location

Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Daniel Steinbrüchel, Professor

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 15, 2009
• First Posted: May 18, 2009
• Study Start: May 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: May 17, 2011

Record last verified: 2011-05

Locations

DK (2)