A Dose-ranging Safety and Efficacy Study of Ecallantide t... | NCT00816023

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ecallantide Low Dose	Experimental	target steady state concentration of 0.15 mg/L	Drug: ecallantide
Ecallantide Medium Dose	Experimental	target steady state concentration of 0.75 mg/L	Drug: ecallantide
Ecallantide High Dose	Experimental	target steady state concentration of 2.25 mg/L	Drug: ecallantide
Placebo	Placebo Comparator	placebo	Drug: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ecallantide	Drug	infusion administered IV over the duration of the surgical procedure	Ecallantide High Dose Ecallantide Low Dose Ecallantide Medium Dose

Measure	Description	Time Frame
Cumulative Volume of Packed Red Blood Cells Transfused at 12 Hours Post Surgery		Start of surgery up to 12 hours after the end of surgery

Measure	Description	Time Frame
Treatment-emergent Adverse Events		Over the duration of the study.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent (by study subject or appropriate legal representative) prior to any study-related procedure not part of normal medical care
Planned primary CABG surgery including the use of cardio-pulmonary bypass.

Exclusion Criteria:

Planned concomitant surgery including ASD repair, valve replacement, carotid endarterectomy, CABG combined procedures or any repeat sternotomy;
Body weight <55 kg;
Planned hypothermia (<28ºC);
Planned transfusion in the peri-operative or post-operative periods;
Planned transfusion of pre-operatively donated autologous blood;
Female subjects who are pregnant or lactating;
Planned use of desmopressin, lysine analogs, atrial natriuretic hormone or recombinant activated Factor VII;
Planned use of corticosteroids in the pump prime solution;
Ejection fraction <30% within 90 days prior to surgery;
Evidence of a myocardial infarction within 5 days prior to surgery;
History of stroke or transient ischemic attack within 3 months prior to surgery;
Hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery;
Serum creatinine >2.0 mg/dL within 48 hours prior to surgery;
Serum hepatic enzymes above 2.5 times the upper limit of normal for the applicable laboratory;
Hematocrit <32% within 48 hours prior to surgery;
Platelet count below the normal range for the applicable laboratory within 14 days prior to surgery;
History of, or family history of, bleeding or clotting disorder or thrombophilia;
History of heparin-induced thrombocytopenia;
Prothrombin time and/or activated partial thromboplastin time >1.5 X normal range;
Serious intercurrent illness or active infection;
Any previous exposure to ecallantide;
Receipt of an investigational drug or device 30 days prior to participation in the current study;
Known allergy to any agent expected to be used in the intra-operative or post-operative periods; and
Administration of: Eptifibatide within 6 hours prior to surgery, Tirofiban HCl within 6 hours prior to surgery, *Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery, Clopidogrel within 5 days prior to surgery, Ticlopidine within 7 days prior to surgery, Abciximab within 5 days prior to surgery, *Bivalirudin, argatroban or lepirudin within 6 hours prior to surgery, *Fondaparinux within 72 hours prior to surgery, Prasugrel within 10 days prior to surgery [*Prophylactic use permitted for the prevention of deep vein thrombosis.]

Name	Affiliation	Role
Alistair Wheeler, MD, MFPM	Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Cardio-Thoracic Surgeons PC		Birmingham	Alabama	35205	United States
Drug Research and Analysis Corporation

Results Section

Participant Flow Module

ID	Title	Description
FG000	Ecallantide Low Dose	target steady state concentration of 0.15 mg/L
FG001	Ecallantide Medium Dose	target steady state concentration of 0.75 mg/L

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cumulative Volume of Packed Red Blood Cells Transfused at 12 Hours Post Surgery

The Modified Intent to Treat population was the basis of this analysis, defined as all randomized subjects who received any amount of study drug and analyzed according to the planned treatment assignment.

Posted

Mean

Standard Deviation

Start of surgery up to 12 hours after the end of surgery

ID	Title	Description
OG000	Ecallantide Low Dose	target steady state concentration of 0.15 mg/L
OG001	Ecallantide Medium Dose	target steady state concentration of 0.75 mg/L
OG002	Ecallantide High Dose	target steady state concentration of 2.25 mg/L
OG003	Placebo

Units	Counts
Participants	OG00065 OG00158 OG00263 OG003

Title

Denominators

Categories

Title	Measurements
	OG000401.9± 624.87 OG001383.1± 620.62 OG002410.3± 639.47 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003		Jonckheere-Terpstra		0.474							95						No	Superiority or Other

Secondary

Treatment-emergent Adverse Events

Analysis conducted on Safety population, defined as all subjects randomized and received any study drug. Treatment groups are based on actual treatment received.

Posted

Number

participants

Over the duration of the study.

ID	Title	Description
OG000	Ecallantide Low Dose	target steady state concentration of 0.15 mg/L
OG001	Ecallantide Medium Dose	target steady state concentration of 0.75 mg/L
OG002	Ecallantide High Dose	target steady state concentration of 2.25 mg/L
OG003	Placebo

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG0030 events0 affected63 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0013 events3 affected59 at risk EG0022 events2 affected65 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Cardiogenic shock	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Intracardiac thrombus	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Hyperthermia	General disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0021 events1 affected65 at risk EG003
Secretion discharge	General disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Bronchitis	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Cellulitis	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Incision site cellulitis	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Pneumonia	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Post procedural cellulitis	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0002 events2 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Staphylococcal sepsis	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Drug toxicity	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Femoral nerve injury	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0006 events6 affected62 at risk EG0014 events4 affected59 at risk EG0026 events6 affected65 at risk EG003
Vascular graft occlusion	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0012 events2 affected59 at risk EG0020 events0 affected65 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Syncope vasovagal	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Psychotic disorder	Psychiatric disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 11.1	Systematic Assessment	EG0002 events2 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Non-cardiogenic pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0020 events0 affected65 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0014 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Hypotension	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0020 events0 affected65 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 11.1	Systematic Assessment	EG00021 events21 affected62 at risk EG00131 events30 affected59 at risk EG00228 events25 affected65 at risk EG00323 events22 affected63 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 11.1	Systematic Assessment	EG0008 events8 affected62 at risk EG0015 events5 affected59 at risk EG0025 events4 affected65 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 11.1	Systematic Assessment	EG0007 events7 affected62 at risk EG0016 events6 affected59 at risk EG0026 events6 affected65 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG00020 events18 affected62 at risk EG00123 events23 affected59 at risk EG00217 events17 affected65 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected59 at risk EG0020 events0 affected65 at risk EG003
Cardiomegaly	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected59 at risk EG0022 events2 affected65 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0007 events7 affected62 at risk EG0018 events8 affected59 at risk EG0029 events9 affected65 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0020 events0 affected65 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0005 events4 affected62 at risk EG0017 events7 affected59 at risk EG0023 events3 affected65 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0008 events7 affected62 at risk EG0016 events5 affected59 at risk EG0022 events2 affected65 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG00024 events24 affected62 at risk EG00124 events24 affected59 at risk EG00220 events20 affected65 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0014 events4 affected59 at risk EG0023 events3 affected65 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0014 events4 affected59 at risk EG0022 events2 affected65 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG00031 events31 affected62 at risk EG00123 events22 affected59 at risk EG00230 events30 affected65 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0009 events8 affected62 at risk EG0015 events5 affected59 at risk EG0025 events5 affected65 at risk EG003
Asthenia	General disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0015 events5 affected59 at risk EG0023 events3 affected65 at risk EG003
Chills	General disorders	MedDRA 11.1	Systematic Assessment	EG0006 events6 affected62 at risk EG0014 events4 affected59 at risk EG0024 events4 affected65 at risk EG003
Generalised oedema	General disorders	MedDRA 11.1	Systematic Assessment	EG00022 events22 affected62 at risk EG00123 events22 affected59 at risk EG00217 events17 affected65 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected59 at risk EG0022 events2 affected65 at risk EG003
Oedema	General disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0014 events4 affected59 at risk EG0022 events2 affected65 at risk EG003
Oedema peripheral	General disorders	MedDRA 11.1	Systematic Assessment	EG0007 events7 affected62 at risk EG0016 events6 affected59 at risk EG0028 events8 affected65 at risk EG003
Pain	General disorders	MedDRA 11.1	Systematic Assessment	EG0006 events5 affected62 at risk EG0013 events3 affected59 at risk EG0027 events5 affected65 at risk EG003
Pyrexia	General disorders	MedDRA 11.1	Systematic Assessment	EG0007 events7 affected62 at risk EG00114 events14 affected59 at risk EG0029 events9 affected65 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0008 events8 affected62 at risk EG0015 events5 affected59 at risk EG0025 events5 affected65 at risk EG003
Incision site pain	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG00020 events18 affected62 at risk EG00119 events18 affected59 at risk EG00217 events14 affected65 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0022 events2 affected65 at risk EG003
Post procedural discharge	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0006 events5 affected62 at risk EG0012 events2 affected59 at risk EG0022 events2 affected65 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0012 events2 affected59 at risk EG0023 events3 affected65 at risk EG003
Procedural nausea	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0014 events4 affected59 at risk EG0021 events1 affected65 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 11.1	Systematic Assessment	EG00043 events42 affected62 at risk EG00136 events36 affected59 at risk EG00244 events44 affected65 at risk EG003
Blood calcium decreased	Investigations	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Blood creatinine increased	Investigations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0024 events4 affected65 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Body temperature increased	Investigations	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0014 events4 affected59 at risk EG0027 events7 affected65 at risk EG003
Breath sounds abnormal	Investigations	MedDRA 11.1	Systematic Assessment	EG0002 events2 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Urine output decreased	Investigations	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0018 events8 affected59 at risk EG0025 events5 affected65 at risk EG003
White blood cell count increased	Investigations	MedDRA 11.1	Systematic Assessment	EG0005 events5 affected62 at risk EG0016 events6 affected59 at risk EG0023 events3 affected65 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0014 events4 affected59 at risk EG0025 events5 affected65 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG00028 events27 affected62 at risk EG00124 events24 affected59 at risk EG00223 events23 affected65 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0014 events3 affected59 at risk EG0024 events4 affected65 at risk EG003
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0009 events9 affected62 at risk EG0016 events6 affected59 at risk EG0024 events4 affected65 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0006 events6 affected62 at risk EG0015 events5 affected59 at risk EG0022 events2 affected65 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0006 events6 affected62 at risk EG0019 events9 affected59 at risk EG0027 events7 affected65 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0021 events1 affected65 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG0011 events1 affected59 at risk EG0020 events0 affected65 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0016 events5 affected59 at risk EG0023 events3 affected65 at risk EG003
Dizziness	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected59 at risk EG0023 events3 affected65 at risk EG003
Headache	Nervous system disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0025 events5 affected65 at risk EG003
Agitation	Psychiatric disorders	MedDRA 11.1	Systematic Assessment	EG0006 events5 affected62 at risk EG0013 events3 affected59 at risk EG0025 events5 affected65 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 11.1	Systematic Assessment	EG0002 events2 affected62 at risk EG0014 events3 affected59 at risk EG0029 events9 affected65 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 11.1	Systematic Assessment	EG0006 events6 affected62 at risk EG0013 events3 affected59 at risk EG0028 events8 affected65 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 11.1	Systematic Assessment	EG0005 events5 affected62 at risk EG0019 events9 affected59 at risk EG00212 events12 affected65 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG00032 events30 affected62 at risk EG00127 events26 affected59 at risk EG00224 events23 affected65 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0013 events3 affected59 at risk EG0020 events0 affected65 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0002 events2 affected62 at risk EG0014 events4 affected59 at risk EG0027 events7 affected65 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG00026 events24 affected62 at risk EG00121 events18 affected59 at risk EG00214 events13 affected65 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0005 events4 affected62 at risk EG0013 events3 affected59 at risk EG0023 events3 affected65 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0003 events3 affected62 at risk EG0012 events2 affected59 at risk EG0022 events2 affected65 at risk EG003
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected59 at risk EG0021 events1 affected65 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0004 events4 affected62 at risk EG00112 events11 affected59 at risk EG0028 events8 affected65 at risk EG003
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0005 events5 affected62 at risk EG0017 events7 affected59 at risk EG0025 events5 affected65 at risk EG003
Haematoma	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected59 at risk EG0025 events4 affected65 at risk EG003
Hypertension	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG0008 events8 affected62 at risk EG0018 events8 affected59 at risk EG00210 events10 affected65 at risk EG003
Hypotension	Vascular disorders	MedDRA 11.1	Systematic Assessment	EG00025 events24 affected62 at risk EG00126 events25 affected59 at risk EG00231 events28 affected65 at risk EG003

Certain Agreements

ID	Title	Description
BG000	Ecallantide Low Dose	target steady state concentration of 0.15 mg/L
BG001	Ecallantide Medium Dose	target steady state concentration of 0.75 mg/L
BG002	Ecallantide High Dose	target steady state concentration of 2.25 mg/L
BG003	Placebo
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ECALLANTIDE HIGH DOSE	Target steady state concentration of 2.25 mg/L	19	62	62	62
EG001	ECALLANTIDE MEDIUM DOSE	Target steady state concentration of 0.75 mg/L	19	59	59	59
EG002	ECALLANTIDE LOW DOSE	Target steady state concentration of 0.15 mg/L	15	65	65	65
EG003	PLACEBO		15	63	63	63