This is a phase 3, multicenter, randomized, double-blind (third party unblinded) comparison of the efficacy and safety of IV tigecycline with those of IV levofloxacin in subjects hospitalized with 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 IV administration. Subjects will be hospitalized and will receive IV test article for a minimum of 7 days (14 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 and in Bulgaria only < 70 years of age.
• Subjects hospitalized with CAP with a severity that requires IV antibiotic treatment for at least 7 days.
• The presence of fever (within 24 hours before randomization), defined as oral temperature >38degC/100.4degF, axillary temperature >38.1degC/ 100.6degF, tympanic temperature >38.5degC/ 101.2degF, or a rectal/core temperature ≥39debC/102.2degF OR Hypothermia (within 24 hours before randomization), core temperature <35degC/95degF.
• 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 10^9/L (>10,000/mm^3) OR >15% immature neutrophils (bands) regardless of total peripheral WBC count OR Leukopenia with a total WBC count <4.5 x 10^9/L (4500/mm^3); f. Hypoxemia with a PO2 < 60 mm Hg or oxygen saturation < 90% while subject is breathing room air;
• Chest radiograph (posteroanterior and lateral, if possible) within 48 hours before the first dose of IV test article showing the presence of a new infiltrate.
• Subjects must not have received more than one dose of a nonstudy antibacterial agent to treat the current episode of CAP before 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 to respond to a previous course of outpatient therapy with oral antibiotics for this episode of CAP (ie clinical symptoms have worsened after at least 2 full days of therapy) may be enrolled in the study. The decision and reasons for the switch are to be recorded in the source document and case report form (CRF).
• The subject has voluntarily signed and dated the Institutional Review Board/Ethics Committee-approved informed consent form before 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 (eg, life expectancy < 30 days).
• Hospitalization within 14 days before the onset of symptoms.
• Residence in a long-term care facility or nursing home ≥14 days before the onset of symptoms.
• Treatment in an intensive care unit required.
• Concurrent hemodialysis, hemofiltration, peritoneal dialysis or plasmapheresis.
• 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: a) systolic blood pressure < 90 mm Hg for >2 hours despite adequate fluid replacement, with evidence of hypoperfusion or, b) need for sympathomimetic agents to maintain blood pressure. Note: the use of sympathomimetic agents to maintain adequate renal perfusion is allowed.
• Risk factors for torsades de pointes, such as hypokalemia, significant bradycardia (as determined by the investigator), or cardiomyopathy. If the hypokalemia is corrected, subject may be enrolled; however, the potassium level should be monitored closely.
• A deficiency in glucose-6-phosphate dehydrogenase (G6PD) or history of tendinopathy with a fluoroquinolone.
• Known anatomical or pathological bronchial obstruction, or a history of bronchiectasis or post obstructive pneumonia or end-stage Chronic Obstructive Pulmonary Disease (COPD, FEV1 < 30% predicted). Subject with less severe COPD are not excluded.
• Immunosuppressive therapy defined as chronic treatment with known immunosuppressive medications (including use of >10 mg of prednisone or its equivalent per day chronically, ie, for greater than 3 weeks before randomization).
• Receipt of an organ or bone marrow transplant.
• Presence of any of the following: a. Known human immunodeficiency virus (HIV) infection; b. Known or suspected Pseudomonas infection; c. Cystic fibrosis; d. Known or suspected Pneumocystis carinii pneumonia; e. Known or suspected 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 or to 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 10^9/L [<1000/mm^3]); 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 drug taken or investigational device used within 4 weeks before administration of the first dose of the IV test article.
• Outpatient ventilator therapy within 14 days before the onset of symptoms or ventilator therapy required at the time of screening. Note: continuous positive airway pressure (CPAP) is allowed.
• Current 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.
• Subject who are suspected or confirmed to have at baseline viral pneumonia and who are not suspected or confirmed to have also bacterial pneumonia.

Belgium
      Hopital Erasme, BRUXELLES,  1070,  Belgium; Recruiting
      Clin. Universitaires St Luc, BRUXELLES,  1200,  Belgium; Recruiting
Bulgaria
      Hospital "Alexandrovska", Sofia,  1431,  Bulgaria; Recruiting
      5th MHAT, Sofia,  Bulgaria; Recruiting
      Medical Insitute Min. Interior, Sofia,  Bulgaria; Recruiting
      Regional Hospital for Pulmonary Diseases, Rousse,  7000,  Bulgaria; Recruiting
Croatia
      Univ. Hosp. of Infect. Disease, Zagreb,  10000,  Croatia; Recruiting
      General Hospital Sveti Duh, Zagreb,  10000,  Croatia; Recruiting
Czech Republic
      Klinica tbc a respiracnich nemoci - General Faculty Hospital, Ostrava-Poruba,  708 52,  Czech Republic; Recruiting
      Regional Hospital Tabor, Tabor,  390 01,  Czech Republic; Recruiting
      General Faculty Hospital, Praha 2,  120 00,  Czech Republic; Recruiting
      N.M.Sr. Karla Boromejského, Praha 1,  110 00,  Czech Republic; Recruiting
      Masaryk's Hospital, Ústí nad Labem,  401 13,  Czech Republic; Recruiting
      Hospital BMA, Ostrava,  700 30,  Czech Republic; Recruiting
Estonia
      Tartu University Clinic, Tartu,  50406,  Estonia; Recruiting
      North Estonian Hospital, Tallinn,  13419,  Estonia; Recruiting
Germany
      Kreiskrankenhaus Luedenscheid, LUEDENSCHEID,  58515,  Germany; Recruiting
      Zentralklinik Emil von Behring, Berlin,  14109,  Germany; Recruiting
      Klinik fuer Pneumologie und Respiratorische Allergologie, Bochum,  44791,  Germany; Recruiting
      Klinik Bergmannsheil, Bochum,  44789,  Germany; Recruiting
Hungary
      ST. Janos Hospital, Budapest,  1125,  Hungary; Recruiting
      Petz Aldar County Hospital, Gyor,  9002,  Hungary; Recruiting
      Pulmonology Hospital, Törökbálint,  2045,  Hungary; Recruiting
India
      Kasturba Medical College, Mangalore,  575 003,  India; Recruiting
      Seth G.S. Medical College, Mumbai,  400 012,  India; Recruiting
      St. John's Medical College Hospital, Kamataka,  560 034,  India; Recruiting
      Sri Ramchandra Med College Hospital, Chennai,  600 116,  India; Recruiting
Latvia
      Rigas City Clinical Hospital, Riga,  1079,  Latvia; Recruiting
      P Stradins Clinical Hospital, Riga,  1002,  Latvia; Recruiting
Lithuania
      Klaipeda Hospital, Klaipeda,  Lithuania; Recruiting
      Klaipeda Regional Hospital, Klaipeda,  5800,  Lithuania; Recruiting
Romania
      Spitalul Clin Sf. Pantelimon, Bucuresti,  21623,  Romania; Recruiting
      Infect. Clinic Hospital Babes, Bucuresti,  30317,  Romania; Recruiting
      National Institute of Infectious Diseases "Prof. Matei Bals", Bucuresti,  722051,  Romania; Recruiting
      Colentina Clinical Hospital, Bucuresti,  20125,  Romania; Recruiting
      Municipal Clinical Hospital, Constanta,  8700,  Romania; Recruiting
      Clinical Hospital No 13 of Infectious Diseases and Pulmonology, Craiova,  1100,  Romania; Recruiting
Russian Federation
      City Clinical Hospital # 67, Moscow,  123448,  Russian Federation; Recruiting
      Moscow Regional Research Clinical Insitute, Moscow,  121110,  Russian Federation; Recruiting
      Central Clinical Hospital under the Dept. of the President of Russia´s Affairs, Moscow,  121356,  Russian Federation; Recruiting
      Infections Clinical Hospital #1, Moscow,  123367,  Russian Federation; Recruiting
      Institute of Antimicrobial Chemotherapy of Smolensk, Smolensk,  214001,  Russian Federation; Recruiting
Slovakia
      Faculty Hospital Nitra, Nitra,  95001,  Slovakia; Recruiting
      Municipal Hospital -Levice, Levice,  934 01,  Slovakia; Recruiting
      Hospital of F.D. Roosevelt, Banska Bystrica,  97517,  Slovakia; Recruiting
      Faculty Hospital Trnava, Trnava,  91775,  Slovakia; Recruiting
South Africa
      Eben Donges Hospital, Worcester,  South Africa; Recruiting
      Durbanville Medi-Clinic, Durbanville,  South Africa; Recruiting
      Brits Medi-Clinic, Brits,  250,  South Africa; Recruiting
      Vergelegen Medi-Clinic, Somerset West,  7130,  South Africa; Recruiting
      Bloemfontein Mediclinic Hosp., Bloemfontein,  South Africa; Recruiting
      National Hospital, Bloemfontein,  9301,  South Africa; Recruiting
      Bell Street Hospital, Krugersdorp,  1739,  South Africa; Recruiting
Spain
      Hospital Universit. Dr Pesset, Valencia,  46017,  Spain; Recruiting
      Hospital Doctor Josep Trueta, Gerona,  17007,  Spain; Recruiting
      Hospital Clinic i Provincial, Barcelona,  Spain; Recruiting
      Hospital de Conxo, Santiago de Compostela,  15706,  Spain; Recruiting
      Hospital Vall d'Hebron, Barcelona,  8035,  Spain; Recruiting
      CSUB - Division of Infectious Diseases, L'Hospitalet de Llobregat,  8907,  Spain; Recruiting
Ukraine
      Cherkassy Regional Hospital, Cherkassy,  18009,  Ukraine; Recruiting
      F.G. Yanovski Institute of Phithisiology and Pulmonology, Kiev,  3110,  Ukraine; Recruiting
      F.G. Yanovski Institute of Phithisiology and Pulmonology, Kiev,  3110,  Ukraine; Recruiting

Study ID Numbers:  3074A1-313-WW
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  April 15, 2004
ClinicalTrials.gov Identifier:  NCT00081575
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08