This drug is being developed to treat severe sepsis with septic shock and/or respiratory failure. The primary purpose of this study is to identify the optimal dosing regimen and to demonstrate that TAK-242 reduces 28-day all-cause mortality in subject with severe sepsis. This study is being conducted in the United States, Europe, Japan and other countries as may be identified in the posting.

Condition	Intervention	Phase
Sepsis Shock, Septic; Sepsis Syndrome Respiratory Insufficiency	Drug: TAK-242	Phase III

Further Study Details: 

Primary Outcomes: 28-day all-cause mortality
Expected Total Enrollment:  2930

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Clinical evidence of infection
• Subject must meet at least 3 of the following 4 criteria for systemic inflammatory response syndrome: a) core temperature of >38°C (>100.4°F) or <36°C (<96.8°F), b) heart rate of >90 beats per minute, c) Respiratory rate of >20 breaths/min or PaCO2 of <32 mmHg requiring mechanical ventilation or d) total white blood cell (WBC) absolute count >12,000 cells/mm3 or <4,000 cells/mm3, or a WBC differential count showing >10% immature (band) forms.
• Subject must have sepsis with shock and/or respiratory failure with onset manifesting less than or equal to 36 hours before the initiation of study drug infusion.

Exclusion Criteria:

• Subject is less than 18 years of age
• If female, the subject is pregnant or lactating
• Subject is receiving immunosuppressive therapy such as cyclosporine, azothioprine, or cancer-related chemotherapy
• Subject has a granulocyte count of less than 1000/mm3 except if the decreased count is believed to be due to sepsis
• Subject has documented or suspected acute myocardial infarction within the last 6 weeks prior to Pretreatment Period
• Subject has a documented history of moderate to severe chronic heart failure as defined by New York Heart Association (NYHA) Functional Classification III or IV
• Subject is known to be HIV positive with known CD4 count less than or equal to 50/mm3 or has known end-stage processes (eg, progressive multifocal leukoencephalopathy, systemic mycobacterium avium complex infection)
• Subject has known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Subject has methemoglobin level of >5% at Pretreatment Period or has known history of methemoglobinemia
• Subject is moribund and death is considered imminent (within 24 hours of recognition of sepsis)
• Subject is classified as “Do Not Resuscitate” (DNR) or “Do Not Treat” or the subject’s family has not committed to aggressive management of the subject’s condition
• Subject is not expected to survive for 28 days and will not likely be given life support due to a pre-existing, uncorrectable medical condition
• Subject has known esophageal varices, chronic jaundice, cirrhosis, or chronic ascites
• Subject is in a chronic vegetative state or has a similar long-term neurological condition
• Subject has known portal hypertension or Child-Pugh hepatic impairment class C
• Subject has had acute third degree burns involving more than 30% of body surface within 120 hours prior to Pretreatment Period
• Subject has known hypersensitivity to sulfonamides
• Subject has known hypersensitivity to components of TAK-242; ie, is allergic to eggs, egg products, or soybeans
• Subject has participated in any other investigational study within 30 days or 5 half-lives of the drug

Please refer to this study by ClinicalTrials.gov identifier  NCT00143611

Jeffrey T. Sharpe, MS      1-800-948-8002  Ext. 5179 

Louisiana
      Shreveport,  Louisiana,  United States; Recruiting
Japan
      Tokyo,  Japan; Recruiting

Study ID Numbers:  01-04-TL-242-011
Last Updated:  September 1, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00143611
Health Authority: United States: Food and Drug Administration; Japan: Pharmaceuticals and Medical Devices Agency
ClinicalTrials.gov processed this record on 2005-09-06