PK and Safety Evaluation of Daptomycin in Children Ages 2-6 With Proven or Suspected Gram-positive Infections

Study Overview
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Brief Summary
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This is a research study designed to look at the pharmacokinetics (distribution, breakdown, and removal) and tolerability of a single dose of daptomycin in patients aged 2 to 6 years who have infections that are caused by a specific group of bacteria (called Gram-positive bacteria).

Official Title
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An Evaluation of the Pharmacokinetic Profile and Safety of a Single Dose of Daptomycin in Pediatric Subjects Aged Two to Six Years Who Are Concurrently Receiving Standard Antibiotic Therapy for Proven or Suspected Gram-positive Infection

Conditions
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Gram Positive Infection, Concurrent Antibiotic Treatment

Intervention / Treatment
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* Drug: daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written parental (or appropriate legal representative) informed consent prior to any study-related procedure not part of normal medical care; Male or female between the ages of 2 and 6 years old, inclusive; Able to comply with the protocol for the duration of the study; Clinically stable with no evidence of hemodynamic instability (defined as a requirement for pharmacological intervention to manage blood pressure) in the 72 hour window prior to enrollment, and no history or evidence of renal or hepatic compromise; Suspected or diagnosed Gram-positive infection for which the subject is receiving standard antibiotic therapy; A calculated creatinine clearance rate (CLcr) ≥ 80 ml/min/1.73m2 as determined by the Schwartz equation at baseline; Creatine phosphokinase (CPK) levels less than 2X ULN (upper limit of normal) at baseline. Presence of two patent intravenous lines (or comparable means of venous access) prior to dosing on Study Day 1. Exclusion Criteria: Investigational drug use (including daptomycin) or participation in any experimental procedure in the 30 days preceding study entry; Known allergy/ hypersensitivity to daptomycin; History of clinically significant cardiovascular, renal, hepatic, pulmonary (well-controlled asthma is acceptable), gastrointestinal, endocrine, hematologic, autoimmune disease or primary immune deficiency; Pneumonia as sole Gram-positive infection being treated with standard antibiotics; Subjects with clinically significant abnormal laboratory test results [including electrocardiograms (ECGs)], as determined by Investigator; Administration of rifampin within 7 days of study drug administration; Body mass index (BMI) that is outside of the 5th to 95th percentile; Subjects in whom collection of the required blood volume would put them at risk of hemodynamic disturbance (at the discretion of Investigator); History of or current clinically significant (at the discretion of the Investigator) muscular disease, nervous system or seizure disorder; Administration of intramuscular injection between baseline and study drug administration or expected intramuscular injection within 24 hours following dosing; Expected surgical procedure(s) within 24 hours prior to and following dosing; Unexplained muscular weakness, history of peripheral neuropathy, Guillian-Barre or spinal cord injury; History of or current rhabdomyolysis.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>8 mg/kg over a one hour infusion | Drug: daptomycin<br>* i.v. daptomycin given at 8 mg/kg or 10 mg/kg by a one or two hour infusion.<br>* Other names: Cubicin;|
| Experimental: Group 2<br>10mg/kg over a one or two hour infusion | Drug: daptomycin<br>* i.v. daptomycin given at 8 mg/kg or 10 mg/kg by a one or two hour infusion.<br>* Other names: Cubicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmocokinetics of daptomycin |  | From pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of daptomycin |  | Up to 9 days after dosing |