1719. Pharmacokinetics (PK) of Oritavancin in Children: The ORKIDS Trial
Session: Oral Abstract Session: Clinical Trials that May Change Your Practice
Saturday, October 6, 2018: 9:45 AM
Room: S 158
Background: Oritavancin (ORI) is a lipoglycopeptide antibiotic approved in adults as a single 1200 mg intravenous (IV) dose for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive organisms, including methicillin-resistant Staphylococcus aureus. The objective in children is to achieve a PK profile that is similar to that attained in adults. PK and safety data from the first 3 age-specified cohorts are presented.

Methods: The ORKIDS trial is a Phase 1 open-label, sequential, dose-finding study evaluating the PK, safety and tolerability of a single-dose 15 mg/kg (max 1200 mg) IV infusion of oritavancin in children under 18 years. The first three age cohorts (12 to <18 yrs, 6 to <12 yrs, 2 to < 6 yrs) with 8 subjects in each cohort have completed the study. Subjects were required to have a suspected or confirmed Gram-positive bacterial infection for which they received standard-of-care antibiotic therapy. Following a single dose of ORI, PK samples were obtained at 3, 4, 9, 24, 48, 72, and 336 hr after the start of the 3- hr infusion. Plasma concentrations were analyzed by non-compartmental methods. Subjects were evaluated for safety through Day 60. An independent data safety monitoring board evaluated the safety and PK data of each cohort prior to dosing the subsequent cohort.

Results:

PK in children compared to adult data from the SOLO Phase 3 ABSSSI studies (Table 1).

Table 1. Mean PK Parameters from Cohorts 1 – 3 and adults.

Cohort 1

12- <18 years
(n=8)

Cohort 2

6- <12 years
(n=8)

Cohort 3

2-<6 years
(n=8)

Range from Pooled Adult SOLO Trials

Cmax (ug/ml)

127

136

84

106-170

AUC0-inf (h*ug/ml)

4014

3709

1963

1999-3600

Conclusion: In subjects 6 to <18 yrs, a single 15mg/kg dose of ORI appears to be well tolerated and provides a PK profile similar to a single 1200 mg dose in adults. Mean AUC0-inf of 1963 h*ug/ml in subjects 2 to <6 yrs is lower than the targeted exposure range in adults. A higher dose of ORI is currently being studied in this cohort.

John Bradley, MD, FAAP1, Antonio Arrieta, MD, FIDSA2, Paula Bokesch, MD, FAAP3, Karen Fusaro, BA4, David C Griffith, BA5 and Jeffrey S. Loutit, MBChB5, (1)Pediatric Infectious Disease, University of California San Diego, San Diego, CA, (2)Infectious Diseases, CHOC Children's Hospital, Orange, CA, (3)Clinical Research, Melinta Therapeutics, Lincolnshire, IL, (4)Clinical Development, Melinta Therapeutics, Inc., Parsippany, NJ, (5)The Medicines Company, San Diego, CA

Disclosures:

J. Bradley, Melinta Therapeutics: Investigator , Research support .

A. Arrieta, Melinta Therapeutics: Investigator , Research support .

P. Bokesch, Melinta Therapeutics: Consultant , Consulting fee .

K. Fusaro, Melinta Therapeutics: Employee , Salary .

D. C. Griffith, Melinta Therapeutics: Consultant , Consulting fee .

J. S. Loutit, Melinta Therapeutics: Consultant , Consulting fee .

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