Clinical trial NCT02013141: Telavancin Pediatric PK Study (Ages >12 Months to 17 Years)
Official title: An Open-Label Study of the Pharmacokinetics of a Single Dose of Telavancin in Pediatric Subjects Aged 12 Months to 17 Years
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gram-Positive Bacterial Infections
Keywords: Gram positive bacteria
Telavancin
VIBATIV
Pediatric
Pharmacokinetics
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-12-17
Enrollment: 22
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a multicenter, open-label, single-dose pharmacokinetic (PK) study. Infants, children, and adolescents will receive a single 10 mg/kg dose of telavancin infused intravenously (IV) over 60 minutes

Detailed description: This is a multicenter, open-label, single-dose pharmacokinetic (PK) study. Infants, children, and adolescents will receive a single 10 mg/kg dose of telavancin infused intravenously (IV) over 60 minutes in male or female infants, children, and adolescents (\> 12 months to 17 years, inclusive) who require systemic antibiotic therapy for the treatment or prevention of a known or suspected bacterial infection.

Blood samples for PK assessment will be taken as follows: 1.0 hour (±5 min), 1.5 hours (±5 min), 2 hours (±5 min), 6 hours (±30 min), 12 hours (±30 min) and 24 hours (±30 minutes) after the beginning of the infusion. The timing of PK sampling may be optimized after the completion of the older age groups (Cohorts 1-3) to assure that the minimum numbers of samples are collected in the youngest age group \> 12months to \< 24 months. Plasma exposures that will be compared to adult exposures are the primary assessment for this study.

Subject safety will be monitored during the study using standard measures, including physical examinations, vital signs, 12-lead ECGs, clinical laboratory assessments, urinalysis, concomitant medication usage, and adverse event reporting.

Eligibility criteria: Inclusion Criteria:

1. Subject is \> 12 months to 17 years of age (inclusive)
2. Subject's weight is within the 3rd to 97th percentile (inclusive) for age and sex.
3. Written informed consent and assent (if appropriate for older age groups) has been obtained per institutional review board (IRB) policy and requirements, consistent with ICH guidelines.
4. Male and female subjects of reproductive potential (i.e., post-pubertal males and post-menarche females) must agree to use a highly effective method of contraception throughout study period and for 30 days after administration of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., \<1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide; or intrauterine device (IUD) with documented failure rate of \<1% per year; or oral/injectable/implanted hormonal contraceptives used in combination with an additional double-barrier method; or sexual abstinence.
5. Female subjects who are post menarche are required to have a negative serum pregnancy test before the administration of study drug.
6. Subject requires or recently completed systemic antibiotic therapy for the treatment or prevention of a known or suspected bacterial infection. If completed, the last administered dose of systemic antibiotic must be within 24 hours of enrollment.

Exclusion Criteria:

1. Subject has an estimated creatinine clearance \<50 mL/min/1.73 m2 (Schwartz equation).
2. Any clinically significant abnormal laboratory value, including hematology, chemistry, or urinalysis that in the judgement of the investigator would make it difficult to assess the pharmacokinetic profile and safety of a single dose of telavancin or would compromise the safety of the subject.
3. Any clinically significant medical history, abnormal physical examination finding, or vital sign measurement, including evidence of hemodynamic instability or significant collections of fluid outside normal vascular and tissue compartments (e.g., large pleural effusions, ascites), that in the judgement of the investigator would make it difficult to assess the pharmacokinetic profile or safety of a single dose of telavancin or would compromise the safety of the subject.
4. Subject has clinically relevant cardiac abnormality, in the opinion of the investigator, such as:

   1. A mean QTcF \>440 msec, congenital long QT syndrome, second or third degree heart block at rest.
   2. Hemodynamically significant heart disease, eg, hemodynamically unstable congenital heart defect, uncompensated heart failure, uncorrected abnormal calcium, hyperkalemia, or any other unstable cardiac condition.
   3. An arrhythmic heart condition requiring medical therapy
5. Subject is receiving an anticoagulant AND requires specific coagulation testing (Prothrombin Time/International Normalized Ratio, Activated Partial Thromboplastin Time, Activated Clotting Time, or Coagulation Based Factor X Activity Assay) within 24 hours of receiving the telavancin dose. NOTE: Although telavancin does not interfere with coagulation, it interferes with some assays used to monitor coagulation.
6. Subjects who are receiving concomitant vancomycin treatment should not be assessed for vancomycin serum concentrations within 24 hours of receiving the Telavancin dose. NOTE: Telavancin might interfere with some Vancomycin therapeutic drug monitoring assays. Caution should be exercised when interpreting vancomycin drug monitoring levels in the presence of telavancin.
7. Subject has a history of allergies or hypersensitivities to glycopeptide antibiotics (e.g., vancomycin), telavancin, or the formulation excipients.
8. Subject requires, or is anticipated to require, concomitant \[within 24 hours before or 24 hours following the single dose of study medication (telavancin)\] administration of agents that in the clinical judgment of the investigator increase the risk of torsade de pointes.
9. Subject is considered unlikely to comply with the study procedures.
10. Subject was treated with an investigational drug within 30 days or five half-lives, whichever is longer, before study entry.
11. Subject has any other condition that, in the opinion of an investigator, would confound or interfere with evaluation of safety of the investigational drug, or prevent compliance with the study protocol.

Primary outcomes:
measure: Pharmacokinetics- Area Under the Curve Extrapolated to Infinity for the Plasma Concentration Versus Time Curves for Telavancin
timeFrame: 1.0, 1.5, 2.0, 6.0, 12.0, 24.0 hours
measure: Pharmacokinetics- Maximum Plasma Concentration of Telavancin
timeFrame: 1.0, 1.5, 2.0, 6.0, 12.0, 24.0 hours
measure: Pharmacokinetics- Time to Maximum Plasma Telavancin Concentration
timeFrame: 1.0, 1.5, 2.0, 6.0, 12.0, 24.0 hours
measure: Pharmacokinetics- Terminal Elimination Half-life for Plasma Telavancin
timeFrame: 1.0, 1.5, 2.0, 6.0, 12.0, 24.0 hours
measure: Pharmacokinetics- Area Under the Curve From Time Zero to the Last Sample for the Telavancin Plasma Concentration Versus Time Curve
timeFrame: 1.0, 1.5, 2.0, 6.0, 12.0, 24.0 hours
Secondary outcomes:
measure: Safety- Number of Treatment-emergent Adverse Events.
timeFrame: Day 0 (screening) through follow-up on Day 8 (+/- 1 day)
measure: Safety- Number of Subjects With Treatment-emergent Adverse Events
timeFrame: Day 0 (screening) through follow-up on Day 8 (+/- 1 day)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Children's Hospital
state: Ohio
Study officials:
affiliation: Cumberland Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: