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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective Coronary Artery Bypass Graft Surgery

14. juni 2012 opdateret af: The Medicines Company

A Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective CABG Surgery

The purpose of this study is to demonstrate that periprocedural infusion of escalating doses of MDCO-2010 is safe and tolerated in patients undergoing elective CABG surgery, to characterize the single dose pharmacokinetics of MDCO-2010, to investigate the effect of MDCO-2010 on pharmacodynamics (biomarkers of fibrinolysis and coagulation parameters), and to investigate the effect on exploratory clinical endpoints of bleeding, transfusion requirements and reexploration.

Studieoversigt

Detaljeret beskrivelse

This protocol describes a study of the investigational drug MDCO-2010 as a haemostasis modulator in patients undergoing elective Coronary Artery Bypass Graft (CABG) surgery involving a cardiopulmonary bypass (CPB).

Perioperative bleeding is a serious complication that adversely affects the morbidity and mortality of cardiac surgery. To alleviate this complication, prophylactic antifibrinolytic therapies are now widely accepted as a strategy to inhibit excessive fibrinolysis.

MDCO-2010, a synthetic small molecule, is a direct inhibitor of plasmin and plasma kallikrein. Both of these have been implicated with impaired haemostasis. In addition, potent inhibition of coagulation factors Xa, XIa and activated Protein C has been demonstrated. Thus, MDCO-2010 has the potential to mitigate excessive fibrinolysis and thrombin generation during cardiac surgery involving a cardiopulmonary bypass. In particular the latter is supposed to provide additional benefits beyond reducing transfusion requirements.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

32

Fase

  • Fase 2

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria

  • Men, aged 18 to 80 years or
  • Post-menopausal women, aged up to 80 years. Postmenopausal status defined as ≥ 1 year since last menstruation in women with no medical history of hysterectomy or women with a medical history of bilateral oophorectomy
  • Planned elective, isolated primary CABG surgery with more than 1 graft, including the use of cardiopulmonary bypass
  • Written informed consent prior to any study-related procedure not part of normal medical care

Exclusion Criteria

Patients may not meet any of the following exclusion criteria:

  • Planned concomitant surgery including atrial septal defect (ASD) repair, valve replacement, carotid endarterectomy, aortic surgery, any combined procedure or any repeat sternotomy
  • Planned Off-pump CABG
  • Body weight < 55 kg or > 110 kg
  • Planned hypothermia < 28°C
  • Major surgical procedures within 30 days of entry
  • Placement of drug-eluting stent (DES) within 12 months or of bare-metal stent (BMS) within 6 weeks of entry in a vessel which is not intended to be grafted
  • Ejection fraction < 35%
  • Preoperative coagulation abnormalities

    • Platelet count < 100,000/cubic mm, or
    • INR > 1.5 or Quick < 40%, or
    • activated partial thromboplastin time (aPTT) > 1.5 x upper limit of normal (ULN)
  • Preoperative Hb < 11 g/dL for male patients or < 10 g/dL for female patients
  • Patient refusal to receive donor blood products if necessary
  • Administration of thienopyridines within 5 days prior to surgery Administration of warfarin within 5 days prior to surgery
  • Administration of tirofiban or eptifibatide within 24 hours or administration of abciximab within 5 days prior to surgery
  • Administration of fondaparinux within 24 hours prior to surgery
  • Creatinine clearance (calculated using Cockroft-Gault equation) < 60 mL/min
  • Planned intraoperative use of tranexamic acid or of ε-aminocaproic acid
  • History of stroke or transient ischemic attack within 3 months prior to entry
  • Known heparin-induced thrombocytopenia
  • Known history of thrombophilia, eg, deep vein thrombosis (DVT) with pulmonary embolism
  • Active liver disease
  • Any condition requiring chronic immunosuppressive medication
  • Receipt of an investigational drug or device 30 days prior to entry
  • Any other condition which, in the opinion of the investigator, would prevent a patient's participation in the study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Cohort 1
3 patients: loading dose 0.005 mg/kg; infusion 0.0125 mg/kg/h; pump prime 0.02 mg
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andre navne:
  • CU-2010
Eksperimentel: Cohort 2
3 pts: loading dose 0.011 mg/kg; infusion 0.0250 mg/kg/h; pump prime 0.04 mg
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andre navne:
  • CU-2010
Eksperimentel: Cohort 3
6 patients: loading dose 0.027 mg/kg; infusion 0.0625 mg/kg/h; pump prime 0.09 mg
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andre navne:
  • CU-2010
Eksperimentel: Cohort 4
6 patients: loading dose 0.054 mg/kg; infusion 0.1250 mg/kg/h; pump prime 0.18mg
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andre navne:
  • CU-2010
Eksperimentel: Cohort 5
6 patients: loading dose 0.108 mg/kg; infusion 0.2500 mg/kg/h; pump prime 0.35 mg
MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery
Andre navne:
  • CU-2010
Placebo komparator: Placebo
8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion
Commercially available NaCl

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of Adverse Events
Tidsramme: 7 days (day of surgery to day 7)
Number of patients experiencing Adverse Events
7 days (day of surgery to day 7)
Incidence of Serious Adverse Events
Tidsramme: 7 days (day of surgery to day 7)
Number of patients experiencing Serious Adverse Events
7 days (day of surgery to day 7)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Ledende efterforsker: Lars Englberger, PD Dr. Med., University Hospital Inselspital, Bern

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. november 2010

Primær færdiggørelse (Faktiske)

1. maj 2011

Studieafslutning (Faktiske)

1. juni 2011

Datoer for studieregistrering

Først indsendt

10. februar 2012

Først indsendt, der opfyldte QC-kriterier

14. februar 2012

Først opslået (Skøn)

17. februar 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

19. juli 2012

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. juni 2012

Sidst verificeret

1. juni 2012

Mere information

Begreber relateret til denne undersøgelse

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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