Pharmacokinetics (PK) and Safety Evaluation of Daptomycin in Children Ages 3-24 Months With Proven or Suspected Gram-positive Infections or Peri-Operative Subjects Receiving Prophylactic Antibiotics

An Evaluation of the Pharmacokinetic Profile and Safety of a Single Dose of Daptomycin in Pediatric Subjects Aged 3 Months to Twenty-Four Months Who Are Concurrently Receiving Standard Antibiotic Therapy for Proven or Suspected Bacterial Infection Including Peri-Operative Prophylactic Use of Antibiotics

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 3 months to 24 months who have proven or suspected infections that are caused by a specific group of bacteria (called Gram-positive bacteria)or perioperative subjects that are receiving prophylactic antibiotics .

Study Overview

• Status: Completed
• Conditions: Gram Positive Bacterial Infection
• Intervention / Treatment: Drug: Daptomycin

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • University of Louisiana at Monroe
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital and Clinics
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Children's Hospital
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written parental (or appropriate legal representative) informed consent prior to any study-related procedure not part of normal medical care; 2.1 Male or female between the ages of 3 months and 24 months, inclusive; 3. Able to comply with the protocol for the duration of the study; 4.1 Clinically stable with no evidence of hemodynamic instability (defined as a requirement for inotropic or vasodilatory support to manage blood pressure) in the 24 hour window prior to first dose, and no history or evidence of renal or hepatic compromise; 5.1 Suspected or diagnosed bacterial infection for which the subject is receiving standard antibiotic therapy; including prophylactic use of antibiotics peri-operatively; 6. A calculated creatinine clearance rate (CLcr) ≥ 80 ml/min/1.73m2 as determined by the Schwartz equation at baseline; 7. Creatine phosphokinase (CPK) levels less than 2X ULN (upper limit of normal) at baseline; 8.1 Presence of two patent intravenous lines (or comparable means of venous or arterial access)prior to dosing on Study Day 1. A single intravenous line (or comparable means of venous access) is acceptable for both drug administration and sample collection if reasonable effort to gain a second line is unsuccessful. The line must be flushed as described in Appendix B of the protocol prior to obtaining PK samples. PK sample can be obtained from a peri-operatively placed arterial line. Arterial PK samples should be indicated on the CRF.

Exclusion Criteria:

1. Investigational drug use (including daptomycin) or participation in any experimental procedure in the 30 days preceding study entry;
2. Known allergy/ hypersensitivity to daptomycin; 3.1 History of clinically significant, renal, hepatic, autoimmune disease or primary immune deficiency;

4. Deleted 5. Subjects with clinically significant abnormal laboratory test results (including ECGs), as determined by Investigator; 6. Administration of rifampin within 7 days of study drug administration; 7. Deleted 8. Subjects in whom collection of the required blood volume would put them at risk of hemodynamic disturbance (at the discretion of Investigator); 9. Deleted; 10.1 Planned administration of intramuscular injection within 12 hours following study administration unless approved by the Medical Monitor; 11. Deleted 12.1 Guillian-Barre or spinal cord injury; 13. 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Group 1: Ages 13 months to 24 months inclusive. Six subjects dosed at 6 mg/kg as a 30 minute infusion.	Drug: Daptomycin; Group 1: Ages 13 months to 24 months inclusive. Six subjects dosed at 6 mg/kg as a 30 minute infusion; Group 2:Ages 7 months to 12 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion; Group 3: Ages 3 months to 6 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion.; Other Names: Cubicin
Experimental: Group 2; Group 2: Ages 7 months to 12 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion	Drug: Daptomycin; Group 1: Ages 13 months to 24 months inclusive. Six subjects dosed at 6 mg/kg as a 30 minute infusion; Group 2:Ages 7 months to 12 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion; Group 3: Ages 3 months to 6 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion.; Other Names: Cubicin
Experimental: Group 3; Group 3: Ages 3 months to 6 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion.	Drug: Daptomycin; Group 1: Ages 13 months to 24 months inclusive. Six subjects dosed at 6 mg/kg as a 30 minute infusion; Group 2:Ages 7 months to 12 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion; Group 3: Ages 3 months to 6 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion.; Other Names: Cubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK of single dose daptomycin in subjects between 3 and 24 months who are receiving standard antibiotic therapy for a Gram-positive infection, including subjects that are receiving prophylactic antibiotics peri-operatively.	Two years

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of a single dose daptomycin in subjects between 3 and 24 months, who are receiving standard antibiotic therapy for a Gram-positive infection, including subjects that are receiving prophylactic antibiotics peri-operatively.	Two years

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Paula Bokesch, MD, Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• Bradley JS, Benziger D, Bokesch P, Jacobs R. Single-dose pharmacokinetics of daptomycin in pediatric patients 3-24 months of age. Pediatr Infect Dis J. 2014 Sep;33(9):936-9. doi: 10.1097/INF.0000000000000318.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2010
• Primary Completion (Actual): March 20, 2012
• Study Completion (Actual): March 20, 2012

Study Registration Dates

• First Submitted: November 23, 2009
• First Submitted That Met QC Criteria: November 24, 2009
• First Posted (Estimate): November 25, 2009

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

• Keywords: Gram Positive Infection; Concurrent Antibiotic Treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Gram-Positive Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 3009-018; DAP-PEDS-09-01 (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