Trial Outcomes & Findings for Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability of Tigecycline in Patients 8 to 11 Years of Age (NCT NCT00488345)

Last Updated: 2012-10-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)

Results posted on

2012-10-24

Participant Flow

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

Participant milestones

Participant milestones
Measure	Tigecycline 0.75 mg/kg 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Overall Study STARTED	17	21	20
Overall Study COMPLETED	17	17	17
Overall Study NOT COMPLETED	0	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Tigecycline 1 mg/kg 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Overall Study Adverse Event	1	1
Overall Study Unable to administer antibiotics at home	1	0
Overall Study Institutional Review Board review	0	1
Overall Study Surgical team recommendation	1	0
Overall Study Parent/legal guardian request	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tigecycline 0.75 mg/kg n=17 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=21 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=20 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours	Total n=58 Participants Total of all reporting groups
Age Continuous	10.21 years STANDARD_DEVIATION 1.15 • n=5 Participants	10.20 years STANDARD_DEVIATION 1.06 • n=7 Participants	9.72 years STANDARD_DEVIATION 0.94 • n=5 Participants	10.04 years STANDARD_DEVIATION 1.05 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	31 Participants n=4 Participants
Selected Serious Infections Community Acquired Pneumonia	7 participants n=5 Participants	8 participants n=7 Participants	4 participants n=5 Participants	19 participants n=4 Participants
Selected Serious Infections Complicated Intra-abdominal Infection	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants	24 participants n=4 Participants
Selected Serious Infections Complicated Skin and Skin Structure Infection	4 participants n=5 Participants	7 participants n=7 Participants	4 participants n=5 Participants	15 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)

Population: 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.

Outcome measures

Outcome measures
Measure	Tigecycline 0.75 mg/kg n=17 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=19 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=16 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Maximum Observed Plasma Concentration (Cmax)	456 ng/mL Standard Deviation 347	1515 ng/mL Standard Deviation 1457	2599 ng/mL Standard Deviation 3643

PRIMARY outcome

Timeframe: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)

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

Time of peak concentration taken directly from the observed data.

Outcome measures

Outcome measures
Measure	Tigecycline 0.75 mg/kg n=17 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=19 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=16 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.6 hours Standard Deviation 0.2	0.5 hours Standard Deviation 0.1	0.8 hours Standard Deviation 0.6

PRIMARY outcome

Timeframe: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)

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

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.

Outcome measures

Outcome measures
Measure	Tigecycline 0.75 mg/kg n=16 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=18 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=13 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Area Under the Curve (AUCτ) From Time Zero to Time of Estimated Concentration at 12 Hours	1650 ng*h/mL Standard Deviation 529	2557 ng*h/mL Standard Deviation 1196	3196 ng*h/mL Standard Deviation 1704

PRIMARY outcome

Timeframe: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)

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

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.

Outcome measures

Outcome measures
Measure	Tigecycline 0.75 mg/kg n=16 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=18 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=13 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Weight Normalized Drug Clearance (CLW)	0.490 L/hr/kg Standard Deviation 0.130	0.498 L/hr/kg Standard Deviation 0.335	0.528 L/hr/kg Standard Deviation 0.384

PRIMARY outcome

Timeframe: Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy)

Population: mITT

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.

Outcome measures

Outcome measures
Measure	Tigecycline 0.75 mg/kg n=17 Participants 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=21 Participants 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=20 Participants 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Indeterminate: LDOT	0.0 percentage of participants	19.0 percentage of participants	15.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Cure: LDOT	82.4 percentage of participants	52.4 percentage of participants	30.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Improved: LDOT	17.6 percentage of participants	28.6 percentage of participants	55.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Failure: LDOT	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Cure: TOC	94.1 percentage of participants	76.2 percentage of participants	75.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Failure: TOC	5.9 percentage of participants	4.8 percentage of participants	10.0 percentage of participants
Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment Indeterminate: TOC	0.0 percentage of participants	19.0 percentage of participants	15.0 percentage of participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Outcome measures

Outcome data not reported

SECONDARY outcome

Outcome measures

Outcome data not reported

Adverse Events

Tigecycline 0.75 mg/kg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Tigecycline 1 mg/kg

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Tigecycline 1.25 mg/kg

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tigecycline 0.75 mg/kg n=17 participants at risk 0.75 milligram per kilogram (mg/kg) intravenous (IV) infusion every 12 hours	Tigecycline 1 mg/kg n=21 participants at risk 1 milligram per kilogram (mg/kg) IV infusion every 12 hours	Tigecycline 1.25 mg/kg n=20 participants at risk 1.25 milligram per kilogram (mg/kg) IV infusion every 12 hours
Gastrointestinal disorders Abdominal pain	0.00% 0/17 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.	0.00% 0/21 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.	5.0% 1/20 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.
Gastrointestinal disorders Anal fistula	0.00% 0/17 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.	4.8% 1/21 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.	0.00% 0/20 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.
Infections and infestations Postoperative wound infection	5.9% 1/17 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.	0.00% 0/21 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.	0.00% 0/20 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.

Other adverse events

Additional Information

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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.
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