PK of Clindamycin and Trimethoprim-sulfamethoxazole in Infants and Children

Summary

Developmental changes in physiology during childhood influence drug dosing. Failure to account for these changes leads to improper dosing, which is associated with decreased drug efficacy and safety in children. Population physiologically-based pharmacokinetic (PBPK) modeling offers the opportunity to predict optimal drug dosing based on physiologic parameters adjusted for developmental changes.

PBPK models are mathematical constructs that incorporate physiologic processes with drug characteristics and genetic variances to characterize the dose-exposure relationship across the age continuum. These models integrate drug-specific (e.g., metabolism, protein binding) and systems-specific (e.g., organ size, blood flow) information to predict the effect of different factors (e.g., age, genetic variants, disease) on drug exposure. By accounting for these factors and using data from clinical trials to confirm the modeling, PBPK models can reduce the number of children needed for clinical trials while maximizing dose-based efficacy and safety.

This trial will evaluate a platform to prospectively validate population PBPK models in children. The study drugs, clindamycin and Bactrim (aka TMP-SMX), are ideal candidates to evaluate population PBPK models in children due to their differing physico-chemical properties and elimination pathways. In addition, a trial of clindamycin and TMP-SMX has broad clinical applicability, as both drugs are among the most commonly used agents to treat gram-positive infections in infants and children.

Conditions

• Bacterial Infections

Interventions

DRUG

Clindamycin

Route of administration is IV for all Cohorts. Dosing interval is every 8 hrs. for all Cohorts: * Cohort 1; No. Subjects = 5; Age 1-5 months; Dose = 9 mg/kg; * Cohort 2; No. Subjects = 5; Age \>5 months to 1 year; Dose =12 mg/kg; * Cohort 3; No. Subjects = 5; Age \>1-2 years; Dose =12 mg/kg. * Cohort 4; No. Subjects = 4; Age \>2-6 years; Dose =12 mg/kg. * Cohort 5; No. Subjects = 4; Age \>6-12 years; Dose =10 mg/kg. * Cohort 6; No. Subjects = 4; Age \>12-16 years; Dose =10 mg/kg.

DRUG

trimethoprim-sulfamethoxazole

Route of administration is PO for all Cohorts. Dosing interval is every 12 hrs. for all Cohorts: * Cohort 1; No. Subjects = 5; Age 1-5 months; Dose = 6 mg/kg. * Cohort 2; No. Subjects = 5; Age \>5 months to 1 year; Dose = 6 mg/kg. * Cohort 3; No. Subjects = 5; Age \>1-2 years; Dose = 6 mg/kg. * Cohort 4; No. Subjects = 4; Age \>2-6 years; Dose = 6 mg/kg. * Cohort 5; No. Subjects = 4; Age \>6-12 years; Dose = 6 mg/kg. * Cohort 6; No. Subjects = 4; Age \>12-16 years; Dose = 4 mg/kg.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Michael Cohen-Wolkowiez

  lead OTHER

Principal Investigators

• Michael Cohen-Wolkowiez, MD · Duke Clinical Research Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Month

Max Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-11-30

Primary Completion

2018-08-31

Completion

2020-06-30

Countries

• United States

Study Locations