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

Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488345
• Other study ID #: 3074K4-2207
• Status: Completed
• Phase: Phase 2
• First received: June 18, 2007
• Last updated: September 12, 2012
• Start date: December 2007
• Est. completion date: September 2009

Study information

• Verified date: September 2012
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: National Health Research Ethics CouncilUkraine: Ministry of HealthUkraine: State Pharmacological Center - Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 11 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infection
• Intra-Abdominal Infection
• Intraabdominal Infections
• Pneumonia, Bacterial
• Skin Diseases
• Skin Diseases, Bacterial
• Skin Diseases, Infectious

Intervention

Drug:
• Tygacil

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Mexico,  South Africa,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)	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.	Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Time of peak concentration taken directly from the observed data.	Day 3 (immediately post-dose, 0.75, and 2 hours post-dose)	No
Primary	Area Under the Curve (AUCt) From Time Zero to Time of Estimated Concentration at 12 Hours	AUCt: 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.	Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)	No
Primary	Weight Normalized Drug Clearance (CLW)	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) (AUCt). CLW was determined as the ratio of CL/weight.	Day 3 (just before and immediately after infusion, and 0.75, 2, and 6 hours post-dose)	No
Primary	Percentage of Participants With Clinical Response (CR) to Tigecycline at Last Day of Therapy (LDOT) and Test-of-Cure (TOC) Assessment	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.	Day 14 or LDOT, TOC Visit (10 to 21 days after last dose of total antibiotic therapy)	No
Secondary	Population Pharmacokinetic (PK) Model: Volume of Distribution	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.	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	No
Secondary	Population Pharmacokinetic (PK) Model: Clearance	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.	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	No
Secondary	Population Pharmacokinetic (PK) Model: Effect of Weight	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.	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	No