Open-Label, Dose-Finding, Pharmacokinetics, Safety and Tolerability Study of Oritavancin in Pediatric Patients With Suspected or Confirmed Bacterial Infections

Study Overview
=================
Brief Summary
-----------------
The purpose of this Phase 1 trial is to evaluate the pharmacokinetics, safety and tolerability of oritavancin in patients <18 years old with a confirmed or suspected bacterial infection.

Detailed Description
-----------------
This is a Phase 1, multicenter, open-label, PK, safety and tolerability study of oritavancin in pediatric patients (<18 years of age) with suspected or diagnosed Gram-positive bacterial infections or pediatric patients requiring peri-operative prophylactic antibiotics. Approximately 54 patients will be enrolled at 5-10 US centers. This study will include 5 age cohorts and patients will be entered in a stepwise approach starting with the older age cohort (12-<18 years). The starting dose will be IV oritavancin 15 mg/kg. The safety, tolerability and PK data will be reviewed at the completion of each cohort to ensure safety and determine the appropriate dose for the next age cohort. At least 8 patients will be enrolled in each cohort except for the birth to <3 month age cohort which will have at least 16 patients enrolled. Three PK samples will be collected over 14 days. The safety follow-up will complete with a 60-day phone call to the caregiver.

Official Title
-----------------
An Open Label, Dose-finding, Pharmacokinetics, Safety, and Tolerability Study of Oritavancin Single Dose Infusion in Pediatric Patients Less Than 18 Years of Age With Suspected or Confirmed Bacterial Infections (ORKIDS)

Conditions
-----------------
Gram Positive Bacterial Infections

Intervention / Treatment
-----------------
* Drug: Oritavancin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females <18 years of age Neonates must be at least 34 weeks post-conception age Parent or legal guardian has given informed consent, as appropriate; and pediatric patient has given verbal assent where appropriate. Suspected or diagnosed Gram positive bacterial infection for which the subject is receiving standard antibiotic therapy; or peri-operative prophylactic use of antibiotics Intravenous access to administer study drug The subject will be observed in the emergency room or hospital for at least 1 hour after the study drug infusion is completed. Exclusion Criteria: Septic shock or acute haemodynamic instability. History of immune-related hypersensitivity reaction to glycopeptides (such as vancomycin, dalbavancin, televancin, or teicoplanin) or any of their excipients. Subjects who have taken vancomycin, telavancin, teicoplanin or other glycopeptide within 24 hours of screening or who are anticipated to need these drugs within 48 hours after administration of study drug. Subjects who have taken dalbavancin are excluded if taken within the previous 2 weeks or who are anticipated to need dalbavancin within 48 hours after administration of study drug. Females who are of childbearing potential and unwilling to practice abstinence or use at least two methods of contraception or female patients of childbearing who are lactating or have a positive pregnancy test result at screening Males who are unwilling to practice abstinence or use an acceptable method of birth control during the entire study period Any surgical or medical condition which, in the opinion of the investigator, would put the patient at increased risk or is likely to interfere with study procedures or PK of the study drug. Patients whom the investigator considers unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study Treatment with investigational medicinal product or investigational device within 30 days (or 5 times the half-life of the investigational medicine, whichever is longer) before enrollment and for the duration of the study. Any clinically significant disease or condition affecting a major organ system, including but not limited to gastrointestinal, renal, hepatic, endocrinologic, broncho-pulmonary, neurological, metabolic or cardiovascular disease.

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oritavancin<br>Single-Dose IV Oritavancin Diphosphate | Drug: Oritavancin<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameter (Area under the plasma concentration time-curve [AUC]) | PK parameters (AUC) | 336 hours post infusion start time for Cohorts 1-4 and 168 hours for Cohort 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters | PK parameters (Cmax, half-life, tmax, volume of distribution and clearance) | 336 hours post infusion start time for Cohorts 1-4 and 168 hours for Cohort 5 | 
| Safety Endpoint | Safety of oritavancin assessed according to clinical laboratory parameters, and adverse events (AEs) and serious adverse events (SAEs) up to 60 days following termination of the study drug infusion. | Up to Day 60 post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oritavancin, pediatrics, gram positive, bacterial infection, Confirmed, Suspected