Clinical trial NCT00488345: Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability of Tigecycline in Patients 8 to 11 Years of Age
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bacterial Infections
Intra-Abdominal Infection
Pneumonia, Bacterial
Skin Diseases, Bacterial
Skin Diseases, Infectious
Keywords: cIAI
cSSSI
CAP
Child
Lead sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
Sponsor class: INDUSTRY
First posted: 2007-06-20
Enrollment: 59
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)
measure: Area Under the Curve (AUCτ) From Time Zero to Time of Estimated Concentration at 12 Hours
timeFrame: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)
measure: Weight Normalized Drug Clearance (CLW)
timeFrame: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)
measure: Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment
timeFrame: Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy)
Secondary outcomes:
measure: Population Pharmacokinetic (PK) Model: Volume of Distribution
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
measure: Population Pharmacokinetic (PK) Model: Clearance
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
measure: Population Pharmacokinetic (PK) Model: Effect of Weight
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
Other outcomes:
Locations:
city: Long Beach
country: United States
state: California
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Louisville
country: United States
state: Kentucky
city: Flint
country: United States
state: Michigan
city: Jackson
country: United States
state: Mississippi
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Guadalarajara Jalisco
country: Mexico
city: Parow
country: South Africa
city: Pretoria
country: South Africa
city: Pretoria
country: South Africa
city: Temba
country: South Africa
city: Worcester
country: South Africa
city: Taipei
country: Taiwan
city: Vinnitsa
country: Ukraine
state: Vynnitsa
city: Dnipropetrovsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Uzhorod
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Wyeth is now a wholly owned subsidiary of Pfizer
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Purdy J, Jouve S, Yan JL, Balter I, Dartois N, Cooper CA, Korth-Bradley J. Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study. Clin Ther. 2012 Feb;34(2):496-507.e1. doi: 10.1016/j.clinthera.2011.12.010. Epub 2012 Jan 16.