Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability of Tigecycline in Patients 8 to 11 Years of Age

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00488345
• Collaborator: (none)
• Enrollment: 59
• Locations: 36
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To determine the pharmacokinetic profile and to evaluate the safety and tolerability of ascending multiple doses of tigecycline in patients aged 8 to 11 years with selected serious infections; complicated intra-abdominal infections (cIAI), complicated skin and skin structure infections (cSSSI), or community-acquired pneumonia (CAP).

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections; Intra-Abdominal Infection; Pneumonia, Bacterial; Skin Diseases, Bacterial; Skin Diseases, Infectious	Drug: Tygacil	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Ascending Multiple-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Tigecycline in Patients 8 to 11 Years of Age With Selected Serious Infections
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A 0.75 mg/kg (up to a maximum dose of 50 mg for each dose) of tigecycline every 12 hours infused over approximately 30 minutes. Escalation to next dose cohort will occur only after safety and tolerability at preceding dose have been established by sponsor (after tigecycline LDOT data are received) and if at least 5 of 6 PK samples per patient have been received by central laboratory in acceptable condition for 10 to 12 patients in cohort. Treatment period of tigecycline will be a minimum of 3 days (unless patient is considered a treatment failure before this time) and a maximum of 14 days. On or after Day 4, based on investigator's decision, patients can switch to oral antibiotic therapy (to be chosen and provided by the investigator) and discharged after collection of planned PK samples.	Drug: Tygacil
Experimental: B 1 mg/kg (up to a maximum dose of 50 mg for each dose) of tigecycline every 12 hours infused over approximately 30 minutes. Escalation to next dose cohort will occur only after safety and tolerability at preceding dose have been established by sponsor (after tigecycline LDOT data are received) and if at least 5 of 6 PK samples per patient have been received by the central laboratory in acceptable condition for 10 to 12 patients in the cohort. Treatment period of tigecycline will be a minimum of 3 days (unless the patient is considered a treatment failure before this time) and a maximum of 14 days. On or after Day 4, based on investigator's decision, patients can switch to oral antibiotic therapy (to be chosen and provided by the investigator) and discharged after collection of planned PK samples.	Drug: Tygacil
Experimental: C 1.25 mg/kg (up to maximum dose of 50 mg for each dose) of tigecycline every 12 hours infused over approximately 30 minutes. Treatment period of tigecycline will be a minimum of 3 days (unless patient is considered a treatment failure before this time) and a maximum of 14 days. On or after Day 4, based on investigator's decision, patients can switch to oral antibiotic therapy (to be chosen and provided by the investigator) and discharged after collection of planned PK samples.	Drug: Tygacil

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)]

   Cmax: tigecycline serum concentration measured in nanograms per milliliter (ng/mL) determined by a validated liquid chromatography with mass spectrophotometric (LC/MS/MS) detection method. Peak concentration was taken directly from the observed data.

2. Time to Reach Maximum Observed Plasma Concentration (Tmax) [Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)]

   Time of peak concentration taken directly from the observed data.

3. Area Under the Curve (AUCτ) From Time Zero to Time of Estimated Concentration at 12 Hours [Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)]

   AUCτ: AUC between doses from time zero to the time of estimated concentration at 12 hours reported in nanograms * hours divided by milliliters (ng*h/mL) was calculated using the log-trapezoidal rule for decreasing concentrations and the linear-trapezoidal rule for increasing concentrations estimating the 12 hour drug concentration if necessary.

4. Weight Normalized Drug Clearance (CLW) [Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)]

   Weight normalized drug clearance measured in liters per hour per kilogram (L/hr/kg). Drug clearance (CL) was determined as the ratio of dose/area under the concentration-time curve from time zero (start of infusion) to 12 hours (start of next infusion) (AUCτ). CLW was determined as the ratio of CL/weight.

5. Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment [Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy)]

   CR = Cure: resolution of all signs, symptoms (SS) of infection (INF) or improvement, no further antibacterial therapy (AT) necessary; Improved (IMP): SS IMP to extent that switch to oral AT deemed appropriate; Failure: lack of response, required additional AT, initial recovery then deterioration requiring further AT, death due to the INF after day 2, death due to treatment (TR)-related adverse event (AE), required non-routine surgical TR >48 hours after 1st dose of TR due to failure to IMP or clinical worsening. TOC = CR, vital signs, physical exam, laboratory results, concomitant TR, and AEs.

Secondary Outcome Measures

1. Population Pharmacokinetic (PK) Model: Volume of Distribution [3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion]

   Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.

2. Population Pharmacokinetic (PK) Model: Clearance [3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion]

   Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.

3. Population Pharmacokinetic (PK) Model: Effect of Weight [3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion]

   Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Male or female patients aged 8 to 11 years, inclusive, willing and able to complete all activities required for the study

• Have a diagnosis of a serious infection (cIAI, cSSSI or CAP) requiring hospitalization and administration of IV antibiotic therapy during greater than or equal to 5 days

• Other inclusion criteria apply.

Exclusion criteria

• Patients with any concomitant condition or taking any concomitant medication that, in the opinion of the investigator, could preclude an evaluation of safety or efficacy responses or make it unlikely that the anticipated course of therapy or follow-up assessment will be completed (e.g., life expectancy < 30 days).

• Pregnant or breastfeeding female patients and female patients of childbearing potential who are unable or unwilling to take adequate contraceptive precautions.

• Previous participation in this clinical trial.

• Receipt of any investigational drugs or devices (defined as lacking any regulatory agency's approval within 4 weeks before administration of the first dose of tigecycline).

• Endocarditis; presence of an artificial heart valve or infected device that will not be removed.

• Known or suspected hypersensitivity to tigecycline or other compounds related to this class of antibacterial agents (i.e., tetracyclines).

• Known or suspected P. aeruginosa infection.

• Patients receiving immunosuppressive therapy that, in the opinion of the investigator, would decrease the patient's ability to eradicate the infection, including the use of high-dose corticosteroid.

• Receipt of an organ or bone marrow transplant.

• Presence of any of the following laboratory findings: Neutropenia (absolute neutrophil count < 1 × 109/L [< 1000/mm3]) , AST or ALT > 10 × the ULN or bilirubin > 3 × ULN, unless isolated hyperbilirubinemia is directly related to the acute process (for patients with cIAI).

• Patients with any of the following conditions:

• Cystic fibrosis.

• Active tuberculosis.

• Congenital immunodeficiency.

• Meningitis.

• Septic shock.

• Osteomyelitis (suspected or evident).

• Refractory shock syndrome in which hemodynamic parameters cannot be maintained despite adequate supportive therapy.

• Confirmed malignancy with patient receiving an active course of chemotherapeutic agents.

• Known or suspected infection with human immunodeficiency virus (HIV) or positive test result for HIV antibody.

• Known or suspected concomitant bacterial or parasitic infection requiring systemic treatment.

• cSSSI patients, the presence of decubitus ulcers, necrotizing fasciitis, gas gangrene, or skeletal infection;

• CAP patients who have been hospitalized within 14 days before the onset of symptoms;

• CAP Patients: Presence of any of the following for patients with pneumonia:

• Postobstructive pneumonia.

• Pulmonary abscess.

• Empyema.

• Known or suspected pulmonary infection with Pneumocystis carinii.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Long Beach	California	United States	90806
2		Oakland	California	United States	94609
3		Orange	California	United States	92868
4		San Diego	California	United States	92123
5		Tampa	Florida	United States	33606
6		Louisville	Kentucky	United States	40202
7		Flint	Michigan	United States	48503
8		Jackson	Mississippi	United States	39218
9		Omaha	Nebraska	United States	68131
10		New York	New York	United States	10032
11		Durham	North Carolina	United States	27710
12		Akron	Ohio	United States	44308
13		Cincinnati	Ohio	United States	45229-3039
14		Hershey	Pennsylvania	United States	17033-0850
15		Philadelphia	Pennsylvania	United States	19104
16		Pittsburgh	Pennsylvania	United States	15213
17		Salt Lake City	Utah	United States	84108
18		Richmond	Virginia	United States	23298
19		Brussels		Belgium	1090
20		Brussels		Belgium	1200
21		Guadalarajara Jalisco		Mexico	0000
22		Parow		South Africa	7500
23		Pretoria		South Africa	0001
24		Pretoria		South Africa	00082
25		Temba		South Africa	00040
26		Worcester		South Africa	6850
27		Taipei		Taiwan	100
28		Vinnitsa	Vynnitsa	Ukraine	21021
29		Dnipropetrovsk		Ukraine	49100
30		Kharkov		Ukraine	61098
31		Kyiv		Ukraine	0.0405
32		Kyiv		Ukraine	0.1133
33		Kyiv		Ukraine	4209
34		Lviv		Ukraine	79085
35		Uzhorod		Ukraine	88000
36		Vinnitsa		Ukraine	21021

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor, Wyeth is now a wholly owned subsidiary of Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00488345
• Other Study ID Numbers: 3074K4-2207
• First Posted: Jun 20, 2007
• Last Update Posted: Oct 24, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer: cIAI; cSSSI; CAP; Child
• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Intraabdominal Infections; Pneumonia, Bacterial; Skin Diseases, Infectious; Skin Diseases, Bacterial; Skin Diseases; Tigecycline

Study Results

Participant Flow

Pre-assignment Detail	Fifty-nine participants were screened and enrolled in the study, and 58 participants received at least 1 dose of tigecycline.

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Period Title: Overall Study
STARTED	17	21	20
COMPLETED	17	17	17
NOT COMPLETED	0	4	3

Baseline Characteristics

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg	Total
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours	Total of all reporting groups
Overall Participants	17	21	20	58
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.21 (1.15)	10.20 (1.06)	9.72 (0.94)	10.04 (1.05)
Sex: Female, Male (Count of Participants)
Female	9 52.9%	10 47.6%	8 40%	27 46.6%
Male	8 47.1%	11 52.4%	12 60%	31 53.4%
Selected Serious Infections (participants) [Number]
Community Acquired Pneumonia	7 41.2%	8 38.1%	4 20%	19 32.8%
Complicated Intra-abdominal Infection	6 35.3%	6 28.6%	12 60%	24 41.4%
Complicated Skin and Skin Structure Infection	4 23.5%	7 33.3%	4 20%	15 25.9%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Cmax: tigecycline serum concentration measured in nanograms per milliliter (ng/mL) determined by a validated liquid chromatography with mass spectrophotometric (LC/MS/MS) detection method. Peak concentration was taken directly from the observed data.
Time Frame	Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)

Outcome Measure Data

Analysis Population Description

Modified intent to treat (mITT) population: participants who were screened, assigned to study medication and received at least one dose of study medication. N = number of participants with evaluable tigecycline concentration data.

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Measure Participants	17	19	16
Mean (Standard Deviation) [ng/mL]	456 (347)	1515 (1457)	2599 (3643)

2. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description	Time of peak concentration taken directly from the observed data.
Time Frame	Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)

Outcome Measure Data

Analysis Population Description

mITT; N = number of participants with evaluable tigecycline concentration data.

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Measure Participants	17	19	16
Mean (Standard Deviation) [hours]	0.6 (0.2)	0.5 (0.1)	0.8 (0.6)

3. Primary Outcome

Title	Area Under the Curve (AUCτ) From Time Zero to Time of Estimated Concentration at 12 Hours
Description	AUCτ: AUC between doses from time zero to the time of estimated concentration at 12 hours reported in nanograms * hours divided by milliliters (ng*h/mL) was calculated using the log-trapezoidal rule for decreasing concentrations and the linear-trapezoidal rule for increasing concentrations estimating the 12 hour drug concentration if necessary.
Time Frame	Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)

Outcome Measure Data

Analysis Population Description

mITT; N = number of participants with sufficient reported tigecycline concentration data to estimate AUC.

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Measure Participants	16	18	13
Mean (Standard Deviation) [ng*h/mL]	1650 (529)	2557 (1196)	3196 (1704)

4. Primary Outcome

Title	Weight Normalized Drug Clearance (CLW)
Description	Weight normalized drug clearance measured in liters per hour per kilogram (L/hr/kg). Drug clearance (CL) was determined as the ratio of dose/area under the concentration-time curve from time zero (start of infusion) to 12 hours (start of next infusion) (AUCτ). CLW was determined as the ratio of CL/weight.
Time Frame	Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)

Outcome Measure Data

Analysis Population Description

mITT; N = number of participants with sufficient reported tigecycline concentration data to estimate AUC.

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Measure Participants	16	18	13
Mean (Standard Deviation) [L/hr/kg]	0.490 (0.130)	0.498 (0.335)	0.528 (0.384)

5. Secondary Outcome

Title	Population Pharmacokinetic (PK) Model: Volume of Distribution
Description	Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.
Time Frame	3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Separate population pharmacokinetic analysis results are not available for the current study as more than 1 study was involved in this analysis based on pooled data from pediatric studies 3074A1-110 and 3074K4-2207.

Arm/Group Title	Tigecycline 0.75 mg/kg, 1 mg/kg, 1.25 mg/kg
Arm/Group Description	0.75, 1 mg/kg, and 1.25 milligram per kilogram (mg/kg) intravenous (IV) infusions every 12 hours
Measure Participants	0

6. Primary Outcome

Title	Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment
Description	CR = Cure: resolution of all signs, symptoms (SS) of infection (INF) or improvement, no further antibacterial therapy (AT) necessary; Improved (IMP): SS IMP to extent that switch to oral AT deemed appropriate; Failure: lack of response, required additional AT, initial recovery then deterioration requiring further AT, death due to the INF after day 2, death due to treatment (TR)-related adverse event (AE), required non-routine surgical TR >48 hours after 1st dose of TR due to failure to IMP or clinical worsening. TOC = CR, vital signs, physical exam, laboratory results, concomitant TR, and AEs.
Time Frame	Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Tigecycline 0.75 mg/kg	Tigecycline 1 mg/kg	Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	1 milligram per kilogram (mg/kg) IV infusion every 12 hours	1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Measure Participants	17	21	20
Cure: LDOT	82.4 484.7%	52.4 249.5%	30.0 150%
Improved: LDOT	17.6 103.5%	28.6 136.2%	55.0 275%
Failure: LDOT	0.0 0%	0.0 0%	0.0 0%
Indeterminate: LDOT	0.0 0%	19.0 90.5%	15.0 75%
Cure: TOC	94.1 553.5%	76.2 362.9%	75.0 375%
Failure: TOC	5.9 34.7%	4.8 22.9%	10.0 50%
Indeterminate: TOC	0.0 0%	19.0 90.5%	15.0 75%

7. Secondary Outcome

Title	Population Pharmacokinetic (PK) Model: Clearance
Description	Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.
Time Frame	3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Separate population pharmacokinetic analysis results are not available for the current study as more than 1 study was involved in this analysis based on pooled data from pediatric studies 3074A1-110 and 3074K4-2207.

Arm/Group Title	Tigecycline 0.75 mg/kg, 1 mg/kg, 1.25 mg/kg
Arm/Group Description	0.75, 1 mg/kg, and 1.25 milligram per kilogram (mg/kg) intravenous (IV) infusions every 12 hours
Measure Participants	0

8. Secondary Outcome

Title	Population Pharmacokinetic (PK) Model: Effect of Weight
Description	Two compartment model with linear clearance and effect of weight on clearance using pooled PK data from 2 pediatric studies. All concentration-time data were combined and analyzed using population PK methods to investigate potential influence of age, weight, and height (dose, tigecycline concentrations, times, subject weight, height, age, body surface area, serum creatinine, estimated creatinine clearance, serum bilirubin.
Time Frame	3074K4-2207: Day 3 just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose; 3074A1-110: just before and 0.5, 0.75, 1, 2, 3, 4, 8, 12, 24, 36, and 48 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Separate population pharmacokinetic analysis results are not available for the current study as more than 1 study was involved in this analysis based on pooled data from pediatric studies 3074A1-110 and 3074K4-2207.

Arm/Group Title	Tigecycline 0.75 mg/kg, 1 mg/kg, 1.25 mg/kg
Arm/Group Description	0.75, 1 mg/kg, and 1.25 milligram per kilogram (mg/kg) intravenous (IV) infusions every 12 hours
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	mITT population. An Adverse Event(AE) term may be reported as both a serious and a non-serious AE, but are distinct events. AE may = serious for one subject and non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Arm/Group Title	Tigecycline 0.75 mg/kg		Tigecycline 1 mg/kg		Tigecycline 1.25 mg/kg
Arm/Group Description	0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours		1 milligram per kilogram (mg/kg) IV infusion every 12 hours		1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
All Cause Mortality
	Tigecycline 0.75 mg/kg		Tigecycline 1 mg/kg		Tigecycline 1.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tigecycline 0.75 mg/kg		Tigecycline 1 mg/kg		Tigecycline 1.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		1/21 (4.8%)		1/20 (5%)
Gastrointestinal disorders
Abdominal pain	0/17 (0%)		0/21 (0%)		1/20 (5%)
Anal fistula	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Infections and infestations
Postoperative wound infection	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Tigecycline 0.75 mg/kg		Tigecycline 1 mg/kg		Tigecycline 1.25 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)		16/21 (76.2%)		17/20 (85%)
Blood and lymphatic system disorders
Anaemia	0/17 (0%)		0/21 (0%)		1/20 (5%)
Thrombocythaemia	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Cardiac disorders
Wolff-Parkinson-White syndrome	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Gastrointestinal disorders
Abdominal pain	1/17 (5.9%)		1/21 (4.8%)		1/20 (5%)
Abdominal pain upper	0/17 (0%)		0/21 (0%)		1/20 (5%)
Chapped lips	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Diarrhoea	2/17 (11.8%)		1/21 (4.8%)		0/20 (0%)
Haematochezia	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Ileus	0/17 (0%)		0/21 (0%)		1/20 (5%)
Lip dry	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Nausea	3/17 (17.6%)		13/21 (61.9%)		12/20 (60%)
Pancreatitis	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Vomiting	5/17 (29.4%)		11/21 (52.4%)		11/20 (55%)
General disorders
Asthenia	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Catheter site related reaction	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Crepitations	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Pyrexia	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Infections and infestations
Candidiasis	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Oral candidiasis	0/17 (0%)		0/21 (0%)		1/20 (5%)
Pharyngitis streptococcal	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Postoperative wound infection	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Viral upper respiratory tract infection	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Excoriation	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Medical device pain	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Procedural pain	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Wound dehiscence	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/17 (0%)		1/21 (4.8%)		1/20 (5%)
Alanine aminotransferase increased	1/17 (5.9%)		0/21 (0%)		1/20 (5%)
Aspartate aminotransferase increased	1/17 (5.9%)		0/21 (0%)		1/20 (5%)
Bilirubin conjugated increased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Blood alkaline phosphatase increased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Blood amylase increased	1/17 (5.9%)		1/21 (4.8%)		1/20 (5%)
Blood bilirubin increased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Blood calcium decreased	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Blood phosphorus decreased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Blood phosphorus increased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Blood urea increased	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Blood uric acid increased	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Electrocardiogram QT prolonged	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
International normalised ratio increased	0/17 (0%)		1/21 (4.8%)		1/20 (5%)
Lipase increased	0/17 (0%)		2/21 (9.5%)		2/20 (10%)
Platelet count increased	0/17 (0%)		0/21 (0%)		1/20 (5%)
Prothrombin time prolonged	0/17 (0%)		1/21 (4.8%)		1/20 (5%)
Weight decreased	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Metabolism and nutrition disorders
Anorexia	0/17 (0%)		1/21 (4.8%)		1/20 (5%)
Dehydration	0/17 (0%)		0/21 (0%)		1/20 (5%)
Hypokalaemia	0/17 (0%)		0/21 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Myalgia	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Osteopenia	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Nervous system disorders
Convulsion	0/17 (0%)		2/21 (9.5%)		0/20 (0%)
Dysgeusia	0/17 (0%)		0/21 (0%)		1/20 (5%)
Headache	0/17 (0%)		0/21 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Oropharyngeal pain	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Pleural effusion	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Rhinorrhoea	0/17 (0%)		0/21 (0%)		1/20 (5%)
Upper respiratory tract congestion	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Pruritus	1/17 (5.9%)		1/21 (4.8%)		0/20 (0%)
Skin exfoliation	1/17 (5.9%)		0/21 (0%)		0/20 (0%)
Skin ulcer	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Surgical and medical procedures
Post procedural drainage	0/17 (0%)		1/21 (4.8%)		0/20 (0%)
Vascular disorders
Phlebitis	0/17 (0%)		0/21 (0%)		1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.