This is a phase 3, multicenter, randomized, double-blind (third party unblinded) comparison of the efficacy and safety of tigecycline with those of levofloxacin in subjects initially hospitalized with community-acquired pneumonia (CAP). Subjects who have clinical signs and symptoms of CAP and who are hospitalized as a result will be considered for enrollment. Subjects will be randomly assigned (in a 1:1 ratio) to receive either tigecycline or levofloxacin via intravenous (IV) administration. Initially, subjects will be hospitalized and will receive IV test article for a minimum of 3 days (6 doses) and a maximum of 14 days (28 doses).

Condition	Treatment or Intervention	Phase
Pneumonia	Drug: tigecycline  Drug: levofloxacin	Phase III

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

Criteria

Inclusion Criteria:

• Male and female subjects ≥ 18 years of age.
• Subjects hospitalized with CAP for whom IV antibiotic treatment is indicated.
• The presence of fever (within 24 hours prior to randomization), defined as oral temperature >38degreesC/100.4degreesF, axillary temperature >38.1degreesC/100.6degreesF, tympanic temperature >38.5degreesC/ 101.2degreesF, or a rectal/core temperature > 39degreesC/102.2degreesF OR hypothermia (within 24 hours prior to randomization), core temperature < 35degreesC/95degreesF.
• Clinical criteria that include the presence of at least 2 of the following signs and symptoms: a. Cough; b. Production of purulent sputum or a change in the character of sputum consistent with bacterial infection; c. Auscultatory findings of rales and/or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony); d. Dyspnea or tachypnea, particularly if progressive in nature; e. Elevated total peripheral white blood cell count: WBC > 10 X 109/L (>10,000/mm3) OR > 15% immature neutrophils (bands) regardless of total peripheral WBC count OR Leukopenia with a total WBC count: WBC < 4.5 X 109/L (4500/mm3); f. Hypoxemia with a PO2 <60 mm Hg or oxygen saturation < 90% while subject is breathing room air;
• Chest radiograph (posteroanterior and lateral) within 48 hours prior to the first dose of IV test article showing the presence of an infiltrate if previous films are not available, or a new infiltrate if previous films are available.
• Subjects must not have received more than one dose of a non-study antibacterial agent to treat the current episode of CAP prior to the first dose of IV test article. If received, the prior non-study antibiotic must have been a drug with a dosing interval of less than once daily (e.g., every 12 hours, or every 8 hours). A single dose of once daily prior antibiotic is not allowed. Exception: Subjects who failed a previous course of therapy with another antibiotic for this episode of CAP (e.g., the pathogen is resistant to the prior antibiotic therapy, or clinical symptoms have not improved or have worsened after at least 2 full days of therapy) may be enrolled in the study.
• The subject has voluntarily signed and dated the Institutional Review Board/Ethics Committee approved informed consent form prior to any study-specific screening procedures. If any subject is unable to give consent, it may be obtained from the subject’s legal representative in accordance with local laws and regulations.

Exclusion Criteria:

• Any concomitant condition that, in the opinion of the investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy could be completed (e.g., life expectancy < 30 days).
• Hospitalization within 14 days prior to the onset of symptoms. Exception: subjects hospitalized within the previous 24 hours for this episode of CAP may be enrolled.
• Residence in a long-term care facility or nursing home ≥14 days before the onset of symptoms.
• Fine Pneumonia Severity Index score of V or require treatment in an intensive care unit.
• Concurrent hemodialysis, peritoneal dialysis, plasmapheresis, or hemoperfusion.
• Presence of any clinically important central nervous system disease, including seizure disorders or conditions that may predispose the subject to seizures or lower the seizure threshold, or clinically important major psychiatric disorders that may interfere with compliance with the protocol.
• Sustained shock at the time of randomization, defined as systolic blood pressure < 90 mm Hg for > 2 hours despite adequate fluid replacement, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure.
• Risk factors for torsades de pointes, such as hypokalemia, significant bradycardia (as determined by the investigator), or cardiomyopathy. If the hypokalemia is corrected, patients may be enrolled. However, the potassium level should be monitored closely.
• Known anatomical or pathological bronchial obstruction, or a history of bronchiectasis or post obstructive pneumonia.
• Immunosuppressive therapy defined as chronic treatment with known immunosuppressive medications (including use of > 10 mg of prednisone or its equivalent per day over the 3-week period prior to randomization).
• Receipt of an organ or bone marrow transplant.
• Presence of any of the following: a. Known human immunodeficiency virus infection; b. Known or suspected Pseudomonas infection; c. Cystic fibrosis; d. Known or suspected Pneumocystis carinii pneumonia; e. Known Legionella pneumonia; f. Known or suspected active tuberculosis; g. Primary lung cancer; h. Any malignancy metastatic to the lungs;
• Known or suspected hypersensitivity to tigecycline or other tetracyclines, levofloxacin or other quinolones, or any components of the levofloxacin product.
• Failure to respond to levofloxacin (or other quinolone) therapy for the current episode of CAP.
• Presence of any of the following laboratory findings: a. Neutropenia (absolute neutrophil count < 1 X 109/L [<1000/mm3]); b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 10 times the upper limit of normal or total bilirubin > 3 times the upper limit of normal; c. Calculated creatinine clearance (CLCR) <20 mL/min;
• Known or suspected concomitant bacterial infection requiring treatment with an additional systemic antibacterial agent.
• Any investigational drugs taken or investigational devices used within 4 weeks before administration of the first dose of the IV test article.
• Out-patient ventilator therapy within 14 days prior to the onset of symptoms, or ventilator therapy required at the time of screening.
• Use of drugs known to prolong the QT interval, including class Ia and III antiarrhythmics.
• Previous participation in this study.
• Pregnant women or nursing mothers.
• Female subjects of childbearing potential who do not agree to practice sexual abstinence or use a medically acceptable method of contraception throughout the duration of the study and at least 1 month after the last dose of IV test article administration.
• Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study.

Arizona
      St. Lukes Medical Center, Phoenix,  Arizona,  85006,  United States; Recruiting
      Scottsdale Healthcare Shea, Scottsdale,  Arizona,  85260-6709,  United States; Recruiting
California
      Doctor's Medical Center, Modesto,  California,  95350,  United States; Recruiting
      VA Northern California Health Care System, Martinez,  California,  94553,  United States; Recruiting
      Paradise Valley Hospital, National City,  California,  91950,  United States; Recruiting
      Memorial Medical Center, Modesto,  California,  95355,  United States; Recruiting
      Olive View-UCLA Medical Center, Sylmar,  California,  91342,  United States; Recruiting
Colorado
      University of Colorado Hospital, Denver,  Colorado,  80161,  United States; Recruiting
Florida
      Bay Pines VA Medical Center, Bay Pines,  Florida,  33744,  United States; Recruiting
      Alachua General Hospital, Gainesville,  Florida,  32601,  United States; Recruiting
      Orlando Regional Lucerne Hospital, Orlando,  Florida,  32806,  United States; Recruiting
      Orlando Regional Medical Center, Orlando,  Florida,  32806,  United States; Recruiting
      Brandon Regional Hospital, Brandon,  Florida,  33511,  United States; Recruiting
Georgia
      Joseph M. Still Burn Center at Doctors Hospital, Augusta,  Georgia,  30909,  United States; Recruiting
      Baptist Medical Center South, Montgomery,  Georgia,  31604,  United States; Recruiting
      Wellstar Cobb Hospital, Austell,  Georgia,  30106-1174,  United States; Recruiting
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States; Recruiting
Illinois
      St. John's Hospital, Springfield,  Illinois,  62769,  United States; Recruiting
      Memorial Medical Center, Springfield,  Illinois,  62781,  United States; Recruiting
Indiana
      Saint Vincent's Hospital, Indianapolis,  Indiana,  46260,  United States; Recruiting
Kansas
      Wesley Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
Kentucky
      University of Louisville, Louisville,  Kentucky,  40202,  United States; Recruiting
      Veterans Affairs Medical Center, Louisville,  Kentucky,  40206,  United States; Recruiting
Louisiana
      LSU Health Sciences Center, Shreveport,  Louisiana,  71130,  United States; Recruiting
Maryland
      University of Maryland Medical System, Baltimore,  Maryland,  21201,  United States; Recruiting
      Baltimore VA Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Michigan
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States; Recruiting
      Detroit Receiving Hospital, Detroit,  Michigan,  48201,  United States; Recruiting
      Harper University Hospital, Detroit,  Michigan,  48201,  United States; Recruiting
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68918-5300,  United States; Recruiting
New Jersey
      St. Francis Medical Center, Trenton,  New Jersey,  08629-1986,  United States; Recruiting
      Christiana Hospital, Newark,  New Jersey,  19718,  United States; Recruiting
North Carolina
      Forsyth Medical Center, Winston Salem,  North Carolina,  27103,  United States; Recruiting
North Dakota
      Bismark Health and Wellness Center, Bismarck,  North Dakota,  58503,  United States; Recruiting
      St. Alexius Medical Center, Bismark,  North Dakota,  58501,  United States; Recruiting
Ohio
      Genesis Bethesda Hospital, Zanesville,  Ohio,  43701,  United States; Recruiting
      SUMMA Health System, Akron,  Ohio,  44309-2090,  United States; Recruiting
Pennsylvania
      Grand View Hospital, Sellersville,  Pennsylvania,  18960,  United States; Recruiting
      Albert Einstein Medical Center, Philadelphia,  Pennsylvania,  19141,  United States; Recruiting
South Carolina
      Summerville Medical Center, Summerville,  South Carolina,  29485,  United States; Recruiting
      Greenville Hospital System, Greenville,  South Carolina,  29687,  United States; Recruiting
South Dakota
      Odyssey Research Services, Watertown,  South Dakota,  57201,  United States; Recruiting
Tennessee
      Jackson-Madison County General Hospital, Jackson,  Tennessee,  38301,  United States; Recruiting
      Baptist Hospital of East Tennessee, Knoxville,  Tennessee,  37920,  United States; Recruiting
Texas
      University of Texas Health Center - Tyler, Tyler,  Texas,  75708-3154,  United States; Recruiting
      Southwest Texas Methodist Hospital, San Antonio,  Texas,  78229,  United States; Recruiting
Utah
      Salt Lake Regional Medical Center, Salt Lake City,  Utah,  84102,  United States; Recruiting
Virginia
      Sentara Norfolk General Hospital, Norfolk,  Virginia,  23507,  United States; Recruiting
Washington
      Swedish Medical Center, Seattle,  Washington,  98122,  United States; Recruiting

Study ID Numbers:  3074A1-308-WW
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  March 18, 2004
ClinicalTrials.gov Identifier:  NCT00079885
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08