Health Condition 1: null- Acutely hospitalized subjects with a clinical diagnosis of CA-cIAI requiring surgery will be recruited into this study.
Conditions
Interventions
Intervention1: TP-434 for intravenous administration: TP-434-046 was synthesized under current good manufacturing practices and the drug product contains 52.5 mg
(TP-434 free base equivalents) of lyop
Sponsors
Tetraphase Pharmaceuticals Inc
Eligibility
Inclusion criteria
Inclusion criteria: 1. Abdominal pain or discomfort with onset prior to hospitalization 2. Evidence of a systemic inflammatory response with at least one of the following a. Fever (oral temperature greater than 100.4 degree Fahrenheit or 38 degree Celsius) or hypothermia (oral temperature less than 35 degree Celsius/95 degree Fahrenheit). b. Elevated white blood cell (WBC) count (greater than 10,500 per cubic mm) c. Tachycardia (Heart rate greater 90 beats per min) d. Tachypnea (greater than 20 breaths per min) 3. Physical findings consistent with intra-abdominal infection (IAI, defined as localized or diffuse abdominal tenderness (Other supportive findings include presence of a mass, ileus, or rebound tenderness) 4. Clinical diagnosis of community-acquired intra-abdominal infection requiring urgent surgical or percutaneous intervention and not expected to require antibacterial therapy for longer than 14 days 5. At least 18 years and no older than 75 years of age 6. Body mass index (BMI) of less than or equal to 30 kg per meter square 7. Able to provide informed consent. If the patient is unable to provide informed consent, the patientâ??s legally acceptable representative may provide written consent in accordance with institutional guidelines If female: a. Not pregnant or nursing b. If of child-bearing potential will commit to either: i. use at least two medically accepted, effective methods of birth control (e.g., condom, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) during study drug dosing and for 90 days following last study drug dose ii. Sexual abstinence And either 9A. Meets Inclusion Criteria for Pre-operative Enrollment a) Has a sonogram or radiographic imaging result congruent with the diagnosis of cIAI b) Acute surgical or percutaneous intervention (open laparotomy, laparoscopic surgery, or percutaneous drainage of an abscess) is foreseen c) Specimens from the surgical intervention representative of the material associated with infection will be collected by aspiration or tissue sample and sent for culture and susceptibility testing d) Clinical diagnoses consistent with one or more of the following 1. Appendiceal perforation and periappendiceal abscess 2. Diverticular abscess 3. Acute gastric or duodenal perforation (only if operated on greater than 24 hrs after perforation occurs) 4. Traumatic perforation of the intestines (only if operated on greater than 12 hrs after perforation occurs) 5. Abscess or peritonitis due to other perforated viscus, or other gastrointestinal source or 9B. Meets Inclusion Criteria for Intra-operative or Post-operative Enrollment a) Visual confirmation (presence of pus within the abdominal cavity) b) Samples taken for aerobic and anaerobic cultures should be taken by aspiration or tissue sample and immediately inoculated to appropriate media c) Surgical intervention includes open laparotomy, laparoscopic surgery, or percutaneous draining of an abscess d) Initial intervention is adequate, that is a procedure in which all communications between the GI tract and the peritoneal cavity are closed, no necrotic intestine is left, and all infected collections are drained at the initial procedure e) Intra-operative diagnoses includ
Exclusion criteria
Exclusion criteria: Subjects must NOT meet any of the following exclusion criteria 1 Symptoms related to diagnosis of complicated appendicitis (if current diagnosis) for less than 24 hrs prior to current hospitalization 2 Previously hospitalized or admitted to a healthcare facility (including nursing or convalescent home) within the last 6 months 3 Managed by Staged Abdominal Repair or other open abdomen technique 4 Known at study entry to have an IAI caused by a pathogen(s) resistant to one of the study drug antibiotics 5 Acute Physiology and Chronic Health Evaluation (APACHE) II score grater than25 6 Considered unlikely to survive the 6-8 week study period 7 Any rapidly-progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure and septic shock 8 Requirement for vasopressors at therapeutic dosages (ie dopamine greater than 5 μgperkgpermin, any dose of norepinephrine, epinephrine or phenylephrine) to maintain a systolic blood pressure greater than or equal to90 mm Hg or a mean arterial pressure greater than or equal to 70 mm Hg 9 Renal failure as defined as a Threefold increase of serum creatinine to a known previous value or b Decrease in estimated glomerular filtration rate greater than 75 percent to a known previous value or c Urine output of less than 0.3 mL per kg per h for greater than 24 h or d Anuria for greater than 12 h or e Serum creatinine of greater than 4 mg per dL (353.6 μmol per L) with an acute rise of 0.5 mg per dL (42.2 μ mol per L) compared with a previous value 10 Creatinine clearance less than 30 mLpermin as estimated by the Cockcroft-Gault equation (140-age[years]) (Body Weight in kg) (0.85 if female) per (72 Serum Creatinine [mg per dL]); or requires peritoneal dialysis, hemodialysis, or hemofiltration 11 Presence or possible signs of hepatic disease: a Alanine aminotransferase or aspartate aminotransferase greater than 3 x upper limit of normal (ULN) or b Total bilirubin greater than 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute process or c Alkaline phosphatase greater than 3 x ULN or d Subjects with diagnosis of hepatic failure 12 Hematocrit less than 25 percent or hemoglobin less than 8 g per dL 13 Neutropenia with absolute neutrophil count less than 1000 per cubic mm 14 Platelet count less than 50000 per cubic mm 15 Coagulation tests greater than 1.5 x ULN (that is prothrombin time partial thromboplastin time, or international normalized ratio) 16 Patient on anticoagulants prior to hospitalization (excluding low dose aspirin therapy) 17 Immunocompromised condition, including known HIV positivity or AIDS organ (bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroids (eg greater than 40 mg prednisone or equivalent per day for greater than 2 weeks) 18 History of moderate or severe hypersensitivity reactions to tetracyclines carbapenems or β-lactam antibiotics 19 Participation in any investigational drug or device study within 30 days prior to study entry 20 Known or suspected current central nervous system (CNS) disorder that may predispose to seizures or lower seizure threshold (eg severe cerebral arteriosclerosis epilepsy) 21 Previous
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare clinical response at the test-of-cure (TOC) visit in the microbiologically evaluable (ME) population for subjects in the 3 treatment armsTimepoint: primary endpoint of this study will be clinical response at the TOC visit that is 10-14 days after last dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Compare clinical response for subjects in the 3 treatment arms in the following populations a) Modified intent-to-treat (MITT) b) Clinically modified intent-to-treat(c-MITT) c) Microbiologically modified intent-to-treat(m-MITT) d)Clinically evaluable (CE) e)Microbiologically evaluable (ME) (EOT and FU) 2)Compare microbiologic response at EOT and TOC in a) m-MITT,CE,ME population b) To assess safety & tolerability of TP-434 administration c) (PK) parameters after TP-434 infusionTimepoint: Clinical response at end-of-treatment (EOT that is Day 4-7) , TOC( Day 10-14 after last dose of study drug), and follow-up (FU that is 28-42 days after last dose of study drug) visits 1. Microbiologic response for subjects in the 3 treatment arms at EOT and TOC visits 2. Safety endpoints: a) Physical exam including vital signs b) Adverse events c) ECGs at specified time points d) Safety Labs at specified time points | — |
Countries
India, Latvia, Lithuania, Romania, United States of America
Contacts
Public ContactDr Mamta Singh
Outcome results
None listed