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

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

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).

Study Overview

• Status: Completed
• Conditions: Gram Positive Infection; Concurrent Antibiotic Treatment
• Intervention / Treatment: Drug: daptomycin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• Abdel-Rahman SM, Chandorkar G, Akins RL, Bradley JS, Jacobs RF, Donovan J, Benziger DP. Single-dose pharmacokinetics and tolerability of daptomycin 8 to 10 mg/kg in children aged 2 to 6 years with suspected or proved Gram-positive infections. Pediatr Infect Dis J. 2011 Aug;30(8):712-4. doi: 10.1097/INF.0b013e31820fc8e1.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2008
• Primary Completion (Actual): November 20, 2008
• Study Completion (Actual): November 20, 2008

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (Estimate): May 19, 2008

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 3009-023; DAP-PEDS-07-02 (Other Identifier: Cubist Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf