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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00488345
First received: June 18, 2007
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Bacterial Infections
Intra-Abdominal Infection
Pneumonia, Bacterial
Skin Diseases, Bacterial
Skin Diseases, Infectious
Drug: Tygacil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose) ] [ Designated as safety issue: No ]
    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 to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 3 (immediately post-dose, 0.75, and 2 hours post-dose) ] [ Designated as safety issue: No ]
    Time of peak concentration taken directly from the observed data.

  • Area Under the Curve (AUCτ) From Time Zero to Time of Estimated Concentration at 12 Hours [ Time Frame: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose) ] [ Designated as safety issue: No ]
    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.

  • Weight Normalized Drug Clearance (CLW) [ Time Frame: Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment [ Time Frame: Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy) ] [ Designated as safety issue: No ]
    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:
  • Population Pharmacokinetic (PK) Model: Volume of Distribution [ 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 ] [ Designated as safety issue: No ]
    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.

  • Population Pharmacokinetic (PK) Model: Clearance [ 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 ] [ Designated as safety issue: No ]
    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.

  • Population Pharmacokinetic (PK) Model: Effect of Weight [ 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 59
Study Start Date: December 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   8 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488345

  Show 36 Study Locations
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
  More Information

No publications provided by Wyeth is now a wholly owned subsidiary of Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier: NCT00488345     History of Changes
Other Study ID Numbers: 3074K4-2207
Study First Received: June 18, 2007
Results First Received: September 1, 2010
Last Updated: September 12, 2012
Health Authority: South Africa: National Health Research Ethics Council
Ukraine: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
cIAI
cSSSI
CAP
Child

Additional relevant MeSH terms:
Bacterial Infections
Communicable Diseases
Infection
Intraabdominal Infections
Pneumonia, Bacterial
Skin Diseases
Skin Diseases, Bacterial
Skin Diseases, Infectious
Lung Diseases
Pneumonia
Respiratory Tract Diseases
Respiratory Tract Infections
Tigecycline
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014