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

Wyeth

Status and phase: Completed; Phase 2

Conditions: Skin Diseases, Infectious; Skin Diseases, Bacterial; Intra-Abdominal Infection; Pneumonia, Bacterial; Bacterial Infections

Treatments: Drug: Tygacil

Study type: Interventional

Funder types: Industry

Identifiers

NCT00488345

3074K4-2207

Details and patient eligibility

About

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).

Enrollment: 59 patients

Sex: All

Ages: 8 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

A

Experimental group

Description:

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.

Treatment:

Drug: Tygacil

B

Experimental group

Description:

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.

Treatment:

Drug: Tygacil

C

Experimental group

Description:

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.

Treatment:

Drug: Tygacil