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

NCT01535222 | Completed Phase 2 Results DMC

• 1 other identifier: TMC-CU-10-01
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Coronary Artery Bypass Graft; Cardiopulmonary Bypass

Keywords

cardiac surgery; coronary artery bypass graft; cardiopulmonary bypass; haemostasis modulator; blood loss; direct inhibitor of plasmin and plasma kallikrein; CABG; CPB

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  Number of patients experiencing Adverse Events

  7 days (day of surgery to day 7)

• Incidence of Serious Adverse Events

  Number of patients experiencing Serious Adverse Events

  7 days (day of surgery to day 7)

Study Arms (6)

Cohort 1

EXPERIMENTAL

3 patients: loading dose 0.005 mg/kg; infusion 0.0125 mg/kg/h; pump prime 0.02 mg

Drug: MDCO-2010

Cohort 2

EXPERIMENTAL

3 pts: loading dose 0.011 mg/kg; infusion 0.0250 mg/kg/h; pump prime 0.04 mg

Drug: MDCO-2010

Cohort 3

EXPERIMENTAL

6 patients: loading dose 0.027 mg/kg; infusion 0.0625 mg/kg/h; pump prime 0.09 mg

Drug: MDCO-2010

Cohort 4

EXPERIMENTAL

6 patients: loading dose 0.054 mg/kg; infusion 0.1250 mg/kg/h; pump prime 0.18mg

Drug: MDCO-2010

Cohort 5

EXPERIMENTAL

6 patients: loading dose 0.108 mg/kg; infusion 0.2500 mg/kg/h; pump prime 0.35 mg

Drug: MDCO-2010

Placebo

PLACEBO COMPARATOR

8 patients: commercially available NaCl as matching placebo to MDCO-2010 administered as IV infusion

Drug: Placebo

Interventions

MDCO-2010 DRUG

MDCO-2010 solution for infusion. Dosage: Pump priming dose; Loading dose infusion over 6 minutes; Maintenance infusion for duration of surgery

Also known as: CU-2010

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo DRUG

Commercially available NaCl

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Medicines Company: lead

MeSH Terms

Conditions

Hemorrhage

Interventions

CU-2010

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Andreas van de Locht
• Organization: The Medicines Company

andreas.locht@themedco.com

+4989244180862

Study Officials

• Lars Englberger, PD Dr. Med.

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 17, 2012
• Study Start: November 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 19, 2012
• Results First Posted: July 19, 2012

Record last verified: 2012-06