Trial Outcomes & Findings for Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia (NCT NCT00707239)

Last Updated: 2012-07-10

Results Overview

Clinical response: Cure=All initial signs/symptoms of pneumonia (SSx) improved; chest x-ray (CXR) improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death \> study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or \>2 days but before TOC visit for non-pneumonia reason.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])

Results posted on

2012-07-10

Participant Flow

Participant milestones

Participant milestones
Measure	Tigecycline 75 mg Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Overall Study STARTED	37	36	35
Overall Study Treated	36	35	34
Overall Study COMPLETED	18	25	21
Overall Study NOT COMPLETED	19	11	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Tigecycline 75 mg Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Overall Study Adverse Event	5	3	2
Overall Study Death	3	1	3
Overall Study Physician Decision	1	1	2
Overall Study Protocol Violation	0	0	1
Overall Study Lack of Efficacy	1	2	0
Overall Study Randomized, but not treated	1	1	1
Overall Study Other	8	3	5

Baseline Characteristics

Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tigecycline 75 mg n=36 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Total n=105 Participants Total of all reporting groups
Age Continuous	60.31 years STANDARD_DEVIATION 14.82 • n=5 Participants	61.46 years STANDARD_DEVIATION 16.05 • n=7 Participants	64.85 years STANDARD_DEVIATION 15.33 • n=5 Participants	62.16 years STANDARD_DEVIATION 15.37 • n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	16 Participants n=7 Participants	5 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	19 Participants n=7 Participants	29 Participants n=5 Participants	71 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after last day of therapy [LDOT])

Population: CE population included those participants who met specified evaluability criteria for efficacy.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=23 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=20 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=24 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit Cure	69.6 percentage of participants	85.0 percentage of participants	75.0 percentage of participants
Percentage of Participants With Clinical Response in Clinically Evaluable (CE) Population at Test-of-Cure (TOC) Visit Failure	30.4 percentage of participants	15.0 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Population: c-mITT population included all participants who were randomly assigned to receive intravenous study medication and had clinical evidence of hospital-acquired pneumonia (HAP).

Clinical response: Cure=All initial SSx improved; CXR improved/stable; no other antibiotics for pneumonia; no worsening or new SSx. Failure=Persistence or worsening SSx; no clinical improvement or initial improvement with clinically important worsening; other antimicrobials for pneumonia; CXR progression; death \> study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reasons (e.g., lost to follow-up); death in 2 days after 1st dose for any reason, or \>2 days but before TOC visit for non-pneumonia reason.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=36 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit Cure	52.8 percentage of participants	71.4 percentage of participants	52.9 percentage of participants
Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit Failure	27.8 percentage of participants	14.3 percentage of participants	17.6 percentage of participants
Percentage of Participants With Clinical Response in Clinical Modified Intent-to-treat (c-mITT) Population at Test-of-Cure (TOC) Visit Indeterminate	19.4 percentage of participants	14.3 percentage of participants	29.4 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Population: CE population included those participants who met specified evaluability criteria for efficacy. 'n' is signifying those participants who were evaluable for this measure and included in VAP (suffering from VAP) and non-VAP group (not suffering from VAP) for each group respectively.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=23 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=20 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=24 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit VAP: Cure (n = 7, 7, 9)	71.4 percentage of participants	85.7 percentage of participants	77.8 percentage of participants
Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit VAP: Failure (n = 7, 7, 9)	28.6 percentage of participants	14.3 percentage of participants	22.2 percentage of participants
Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit Non-VAP: Cure (n = 16, 13, 15)	68.8 percentage of participants	84.6 percentage of participants	73.3 percentage of participants
Percentage of Participants With Clinical Response in Ventilator Associated Pneumonia (VAP) and Non-VAP Participants at Test-of-Cure (TOC) Visit Non-VAP: Failure (n = 16, 13, 15)	31.3 percentage of participants	15.4 percentage of participants	26.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Population: Microbiologically Evaluable (ME) population:participants who met evaluability criteria for efficacy, had culture taken from infected site before dose 1 of study drug, had at least (\>=)1 pathogen, \>=1 pathogen was susceptible to tigecycline, imipenem/cilastatin regimen; 'n' = those participants who had specified pathogen for each group respectively.

Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for participants with a clinical response of failure; Indeterminate=unable to determine outcome for non-study drug/infection reasons; no baseline isolate; death in 2 days after 1st dose for any reason, or \>2 days but before TOC visit for non-pneumonia reason.

Outcome measures

SECONDARY outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Population: ME population included participants who met specified evaluability criteria for efficacy, had culture taken from the infected site before first dose of study medication and had at least 1 pathogen, and at least 1 baseline pathogen was susceptible to tigecycline and imipenem/cilastatin regimens.

Microbiological response assessed at participant level. Eradication = baseline isolate not present in repeat culture from the original infection site; Presumed Eradication = clinical response of cure precluded the availability of a specimen for culture; Persistence = baseline isolate present in repeat culture from the original infection site; Presumed Persistence = culture data not available for participants with a clinical response of failure; Superinfection = culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=13 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=10 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=15 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit Eradication	61.5 percentage of participants	80.0 percentage of participants	80.0 percentage of participants
Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit Persistence	38.5 percentage of participants	20.0 percentage of participants	13.3 percentage of participants
Percentage of Participants With Microbiological Response at the Participant Level Population at Test-of-Cure (TOC) Visit Superinfection	0.0 percentage of participants	0.0 percentage of participants	6.7 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29 to Day 35 (15 to 21 days after LDOT)

Population: Modified intent-to-treat (mITT) population included all randomized participants who received at least 1 dose of study medication.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=36 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Number of Participants Who Experienced Nausea or Vomiting Nausea	1 participants	3 participants	1 participants
Number of Participants Who Experienced Nausea or Vomiting Vomiting	3 participants	1 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 24 to Day 35 (10 to 21 days after LDOT)

Population: mITT population included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Participants were evaluated for following laboratory parameters: albumin, alkaline phosphatase, amylase, urea (blood urea nitrogen \[BUN\]), total bilirubin, calcium, magnesium, carbon dioxide, international normalized ratio (INR), chloride, creatinine, glucose, lipase, potassium, phosphorus, aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium, total protein, hemoglobin, hematocrit, white blood cells, eosinophils, neutrophils, lymphocytes, platelets, prothrombin time, prothrombin activity and partial thromboplastin time.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=36 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=33 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=33 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Number of Participants With Abnormal Laboratory Examinations	34 participants	31 participants	31 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 14 or LDOT

Potentially clinically significant ECG data: Non-first values greater than 240 millisecond (msec) with increase of greater than or equal to 10 percent (%) from baseline for PR interval; Non-first values greater than or equal to 120 msec for QRS interval; Non-first values greater than 460 msec with increase of greater than or equal to 5% from baseline for corrected QT (QTc) interval; Non-first values greater than 460 msec with increase of greater than or equal to 5% from baseline for QTc using Framingham formula (QTc F).

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=35 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=33 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=33 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Number of Participants With Abnormal Electrocardiogram (ECG)	14 participants	14 participants	14 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3, 4 or 5

Population: CE population included those participants who met specified evaluability criteria for efficacy. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=20 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=19 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Maximum Observed Serum Concentration (Cmax) of Tigecycline	479 nanogram/milliliter (ng/mL) Standard Deviation 327	1217 nanogram/milliliter (ng/mL) Standard Deviation 1070	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3, 4 or 5

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=20 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=19 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Tigecycline	0.5 hrs Interval 0.5 to 8.0	0.5 hrs Interval 0.5 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3, 4 or 5

AUC (0-12) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12). Area under the serum concentration-time curve was derived from the population pharmacokinetic (PK) analysis by using each participant's dose and the post-hoc individual estimated systemic CL, AUC (0-12) = Dose divided by CL.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=20 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=19 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Tigecycline	3.20 ng*hr/mL Standard Deviation 1.28	5.04 ng*hr/mL Standard Deviation 1.31	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3, 4 or 5

Drug clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the blood. It is defined as the volume of serum from which drug can be completely removed per unit of time.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=39 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Clearance (CL) of Tigecycline	22.6 Liter/hr Interval 19.4 to 26.4	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3, 4 or 5

AUC (0-24) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). Area under the serum concentration-time curve was derived from the population pharmacokinetic (PK) analysis by using each participant's dose and the post-hoc individual estimated systemic CL, AUC (0-12) = Dose divided by CL. Model-predicted AUC (0-24) was calculated by multiplying AUC (0-12) by 2.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=20 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=19 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Tigecycline	6.40 mg*hr/mL Standard Deviation 2.55	10.07 mg*hr/mL Standard Deviation 2.61	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29 to 35 (15 to 21 days after LDOT)

AUC (0-24) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). Area under the serum concentration-time curve was derived from the population PK analysis by using each participant's dose and the post-hoc individual estimated systemic CL, AUC (0-12) = Dose divided by CL. Model-predicted AUC (0-24) was calculated by multiplying AUC (0-12) by 2.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=39 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Correlation of AUC (0-24) of Tigecycline With Nausea and Vomiting Experienced nausea (n = 4)	8.668 mg*hr/mL Standard Deviation 4.401	—	—
Correlation of AUC (0-24) of Tigecycline With Nausea and Vomiting Did not experience nausea (n = 35)	8.206 mg*hr/mL Standard Deviation 3.102	—	—
Correlation of AUC (0-24) of Tigecycline With Nausea and Vomiting Experienced vomiting (n = 4)	6.863 mg*hr/mL Standard Deviation 3.065	—	—
Correlation of AUC (0-24) of Tigecycline With Nausea and Vomiting Did not experience vomiting (n = 35)	8.412 mg*hr/mL Standard Deviation 3.205	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Clinical response:Cure =Initial SSx improved;CXR improved/stable;no other antibiotic for pneumonia;no worsening/new SSx. Failure=Persistence/worsening SSx;no clinical improvement/initial improvement with worsening; other antibiotic;CXR progression;death \>study day 2 due to pneumonia. Indeterminate=unable to determine outcome for non-study drug/infection reason;death in 2 days after dose 1 for any reason or \>2 days but before TOC visit for non-pneumonia reason. MIC=lowest drug concentration with no visible growth of microorganism. AUC(0-24)/MIC:reported for cure and failure/indeterminate.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=25 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Correlation of AUC(0-24) to Minimum Inhibitory Concentration (MIC) Ratio (AUC [0-24]/MIC) of Tigecycline With Clinical Outcome Cure (n = 17)	24.3 ratio Standard Deviation 20.4	—	—
Correlation of AUC(0-24) to Minimum Inhibitory Concentration (MIC) Ratio (AUC [0-24]/MIC) of Tigecycline With Clinical Outcome Failure/indeterminate (n = 8)	22.8 ratio Standard Deviation 9.59	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to Day 24 to 35 (10 to 21 days after LDOT)

Population: Data was not analyzed because correlation analysis could not be performed due to insufficient number of participants for whom data for both microbiological outcomes and tigecycline concentration was available.

Microbiological response:Eradication=baseline isolate not present in repeat culture from original infection site;Presumed Eradication=clinical response of cure precluded availability of specimen for culture;Persistence=baseline isolate present in repeat culture from original infection site;Presumed Persistence=culture data not available for participants with clinical response of failure;Superinfection=culture from primary infection site had new pathogen not identified as baseline isolate, clinical response was failure. MIC=lowest drug concentration with no visible growth of microorganism.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 6

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=98 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Maximum Observed Plasma Concentration of Procalcitonin (Cmaxpd) and Predicted Procalcitonin Plasma Concentration at 24 Hours (Cpd,24) and 48 Hours (Cpd,48) Cmax	2.83 ng/mL Standard Deviation 8.29	—	—
Maximum Observed Plasma Concentration of Procalcitonin (Cmaxpd) and Predicted Procalcitonin Plasma Concentration at 24 Hours (Cpd,24) and 48 Hours (Cpd,48) Cpd,24	1.86 ng/mL Standard Deviation 4.54	—	—
Maximum Observed Plasma Concentration of Procalcitonin (Cmaxpd) and Predicted Procalcitonin Plasma Concentration at 24 Hours (Cpd,24) and 48 Hours (Cpd,48) Cpd,48	1.74 ng/mL Standard Deviation 4.12	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 6

Population: Data was not analyzed because there was no apparent change in procalcitonin concentration over time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 44 (30 days after LDOT)

Population: mITT population included all randomized participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for intravenous antibiotic treatment, hospital or ICU stay for each reporting group respectively.

Outcome measures

Outcome measures
Measure	Tigecycline 75 mg n=36 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Duration of Intravenous Antibiotic Treatment, Hospital and Intensive Care Unit (ICU) Stay Intravenous antibiotic treatment (n = 36, 35, 34)	8.00 days Interval 2.0 to 15.0	9.00 days Interval 1.0 to 15.0	8.50 days Interval 1.0 to 15.0
Duration of Intravenous Antibiotic Treatment, Hospital and Intensive Care Unit (ICU) Stay Hospital stay (n = 36, 35, 34)	13.00 days Interval 2.0 to 29.0	13.00 days Interval 1.0 to 26.0	15.50 days Interval 2.0 to 32.0
Duration of Intravenous Antibiotic Treatment, Hospital and Intensive Care Unit (ICU) Stay ICU stay (n = 25, 25, 29)	8.00 days Interval 2.0 to 16.0	9.00 days Interval 1.0 to 24.0	10.00 days Interval 2.0 to 25.0

Adverse Events

Tigecycline 75 mg

Serious events: 12 serious events

Other events: 28 other events

Deaths: 0 deaths

Tigecycline 100 mg

Serious events: 9 serious events

Other events: 25 other events

Deaths: 0 deaths

Imipenem/Cilastatin 1 Gram

Serious events: 10 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tigecycline 75 mg n=13 Participants Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=10 Participants Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=15 Participants Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Escherichia coli: Persistence (n=1,1,2)	100.0 percentage of participants	100.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Streptococcus oralis: Eradication (n=0,0,1)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus oralis.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus oralis.	100.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Acinetobacter calcoaceticus: Eradication (n=3,2,3)	66.7 percentage of participants	50.0 percentage of participants	66.7 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Acinetobacter calcoaceticus: Persistence (n=3,2,3)	33.3 percentage of participants	50.0 percentage of participants	33.3 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Enterobacter cloacae: Eradication (n=0,0,2)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Enterobacter cloacae.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Enterobacter cloacae.	50.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Enterobacter cloacae: Persistence (n=0,0,2)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Enterobacter cloacae.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Enterobacter cloacae.	50.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Escherichia coli: Eradication (n=1,1,2)	0 percentage of participants	0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Haemophilus: Eradication (n=1,0,0)	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Haemophilus.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Haemophilus.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Haemophilus influenzae: Eradication (n=0,1,1)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Haemophilus influenzae.	100.0 percentage of participants	0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Haemophilus influenzae: Persistence (n=0,1,1)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Haemophilus influenzae.	0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Klebsiella oxytoca: Eradication (n=1,0,0)	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Klebsiella oxytoca.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Klebsiella oxytoca.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Klebsiella pneumoniae: Eradication (n=2,2,5)	50.0 percentage of participants	50.0 percentage of participants	80.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Klebsiella pneumoniae: Persistence (n=2,2,5)	50.0 percentage of participants	50.0 percentage of participants	20.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Serratia marcescens: Eradication (n=0,2,0)	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Serratia marcescens.	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Serratia marcescens.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Staphylococcus aureus (SA): Eradication (n=8,6,9)	62.5 percentage of participants	83.3 percentage of participants	88.9 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit SA: Persistence (n=8,6,9)	37.5 percentage of participants	16.7 percentage of participants	11.1 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit MRSA:Eradication (n=4,2,4)	50.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit MRSA:Persistence (n=4,2,4)	50.0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Methicillin-suseptible SA: Eradication (n=4,4,5)	75.0 percentage of participants	75.0 percentage of participants	80.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Methicillin-suseptible SA: Persistence (n=4,4,5)	25.0 percentage of participants	25.0 percentage of participants	20.0 percentage of participants
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Streptococcus anginosus: Eradication (n=1,0,0)	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus anginosus.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus anginosus.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Streptococcus mitis: Eradication (n=1,0,0)	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus mitis.	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus mitis.
Percentage of Participants With Microbiological Response at the Pathogen Level Population at Test-of-Cure (TOC) Visit Streptococcus pneumonia: Eradication (n=1,1,0)	100.0 percentage of participants	100.0 percentage of participants	NA percentage of participants Data was not available since none of the participants in this reporting group were affected with Streptococcus pneumonia.

Serious adverse events
Measure	Tigecycline 75 mg n=36 participants at risk Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 participants at risk Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 participants at risk Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Cardiac disorders Atrial flutter	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Sinoatrial block	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachyarrhythmia	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Ventricular fibrillation	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal necrosis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haematemesis	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oesophageal fistula	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Multi-organ failure	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Systemic inflammatory response syndrome	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Candida sepsis	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Meningitis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Postoperative wound infection	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Septic shock	11.1% 4/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mediastinum neoplasm	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Brain oedema	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemothorax	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Tracheal disorder	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Vascular disorders	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Deep vein thrombosis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Shock	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Tigecycline 75 mg n=36 participants at risk Tigecycline 150 milligram (mg) loading dose intravenously followed by tigecycline 75 mg maintenance dose intravenously approximately every 12 hours (hrs). Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kilogram \[mg/kg\] or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have Pseudomonas aeruginosa (P. aeruginosa) or methicillin-resistant Staphylococcus aureus (MRSA).	Tigecycline 100 mg n=35 participants at risk Tigecycline 200 mg loading dose intravenously followed by tigecycline 100 mg maintenance dose intravenously approximately every 12 hrs. Ceftazidime 2 gram intravenously approximately every 8 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and vancomycin placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.	Imipenem/Cilastatin 1 Gram n=34 participants at risk Imipenem/cilastatin 1 gram intravenously approximately every 8 hrs. Vancomycin 15 mg/kg intravenously approximately every 12 hrs, an aminoglycoside (tobramycin 7 mg/kg or amikacin 20 mg/kg daily) and ceftazidime placebo intravenously at the start of therapy unless participant did not have P. aeruginosa or MRSA.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Agitation	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	8.3% 3/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.4% 4/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.8% 3/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	17.6% 6/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.8% 3/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	17.6% 6/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Decubitus ulcer	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 3/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	16.7% 6/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	17.1% 6/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.7% 5/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 3/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.8% 3/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypocalcaemia	8.3% 3/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	11.1% 4/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 3/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.8% 4/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	11.1% 4/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.8% 3/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukocytosis	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Lipase increased	8.3% 3/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 3/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Liver disorder	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.4% 4/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Oxygen saturation decreased	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Phlebitis	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Postoperative wound infection	5.6% 2/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	8.3% 3/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.4% 4/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 2/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	11.1% 4/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.8% 4/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.