Cefadroxil and Cephalexin Drug Levels and Dosing in Pediatric Musculoskeletal Infections

NCT03802552 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-2142
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to figure out the best doses for two antibiotics (called cefadroxil and cephalexin) when they are used to treat bone, joint, or muscle infections in children. In order to do this, the study will collect data about children admitted to Children's Hospital Colorado who have these types of infections. During the study, these patients will receive doses by mouth of each of these antibiotics, in addition to an IV antibiotic (given through a vein) used to treat their infection. After the dose of the first antibiotic, blood samples will be drawn every few hours to measure how much of the drug is still in their body, until it is all gone. After the first antibiotic is out of the patient's body, the same will be done for the second antibiotic. Measurements, in the lab, of how much of these antibiotics are needed to kill the most common bacteria causing these infections, which is a type of "Staph" bacteria called "MSSA", will be taken. Finally, the blood levels of the antibiotics and the information from the lab tests about the Staph bacteria will be used to calculate how much and how often of the antibiotic should be given to children with bone, joint, or muscle infections. Currently, these types of infections are treated with an antibiotic that children have to take four times every day. The goal of this study is to find an antibiotic that children can take only two or three times per day.

Conditions

Osteomyelitis; Septic Arthritis; Pyomyositis

Outcome Measures

Primary Outcomes (1)

• Time above Minimum Inhibitory Concentration (T > MIC)

  As a surrogate of treatment efficacy for cefadroxil and cephalexin, the investigators will measure the time that free serum concentrations (T \> MIC) of cefadroxil and cephalexin remain above the minimum inhibitory concentration (MIC) of MSSA. A range of MICs will be directly measured, with an expected range from 0.125 to 4.

  up to 24 hours

Secondary Outcomes (7)

• Clearance (CL/F) of cefadroxil and cephalexin

  Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

• Volume of Distribution (V/F) of cefadroxil and cephalexin

  Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

• Half life (T1/2) of cefadroxil and cephalexin

  Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

• Area under the curve (AUC) of cefadroxil and cephalexin

  Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

• Peak serum drug concentration (Cmax) of cefadroxil and cephalexin

  Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

Study Arms (2)

Cefadroxil then Cephalexin

EXPERIMENTAL

Receive cefadroxil first, then receive cephalexin after washout.

Drug: Cefadroxil; Drug: Cephalexin

Cephalexin then Cefadroxil

EXPERIMENTAL

Receive cephalexin first, then receive cefadroxil after washout.

Drug: Cefadroxil; Drug: Cephalexin

Interventions

Cefadroxil DRUG

oral one-time dose of cefadroxil

Also known as: Duricef

Cefadroxil then Cephalexin; Cephalexin then Cefadroxil

Cephalexin DRUG

oral one-time dose of cephalexin

Also known as: Keflex

Cefadroxil then Cephalexin; Cephalexin then Cefadroxil

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children who are admitted to Children's Hospital Colorado and:
• Are to be treated for a deep musculoskeletal infection (osteomyelitis, septic arthritis, pyomyositis), as determined by their primary medical team
• Are aged 6 months to 18 years

You may not qualify if:

• Patients will be excluded if they:
• Are less than 6 months of age or greater than 18 years of age
• Weigh less than 5.5 kg
• Weigh greater than the 95%ile for age
• Have underlying current renal disease based on medical history
• Have an underlying chronic medical condition-examples include cystic fibrosis, sickle cell anemia, inflammatory bowel disease, pancreatitis, hepatitis, immunodeficiency, cancer, spina bifida, chromosomal abnormalities, cerebral palsy, or metabolic disorders.
• Have a history of significant drug allergy to any beta-lactam antibiotic (e.g. anaphylaxis and/or angioedema)
• Are on an oral cephalosporin at time of enrollment
• Are started on an oral cephalosporin during the study
• o Note: If an enrolled patient is started on an oral cephalosporin prior to completion of the study, they will be removed from the study. However, data obtained prior to their receipt of an oral cephalosporin will still be included in the analysis.
• Are known to be pregnant

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Osteomyelitis; Arthritis, Infectious; Pyomyositis

Interventions

Cefadroxil; Cephalexin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Suppuration; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andrew Haynes, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: January 14, 2019
• Study Start: May 1, 2019
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: June 2, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)