NCT01416350

A Single and Repeat Dose PK/PD Study to Characterise Biomarker Response in Healthy Subjects Treated With Azithromycin

A Single and Repeat Dose Pharmacokinetics/ Pharmacodynamics (PK/PD) Study to Characterise theBiomarker Response in Healthy Subjects Treated With the AntiinflammatoryMacrolide Azithromycin

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This is a two part protocol (Parts A and B) in healthy volunteers evaluating the pharmacokinetics/ pharmacodynamics (PK/PD) of azithromycin to investigate the usefulness of various biomarkers (e.g., Interleukin-10 (IL-10), Granulocyte macrophage colony-stimulating factor (GM-CSF), mature dendritic cell (MDC), with and without ex vivo lipopolysaccharide (LPS) stimulation) as markers of macrolide anti-inflammatory activity. Part A is a randomized, open-label parallel group study evaluating PK/PD of a single azithromycin dose of 250 or 1000 mg. Data from Part A will be used to assess the dose resulting in induction/inhibition of various ex vivo biomarkers relative to a 250 mg dose of azithromycin (the clinical dose used in treatment of neutrophil-induced inflammatory conditions). This information will guide the range of doses to be studied in a first time in humans (FTIH) study of a new chemical entity. Part B is a repeat dose study treating subjects with Azithromycin (250 mg every other day for 3 weeks), the dose approximates that used in the treatment of chronic neutrophil related inflammatory conditions. This information will provide insight into whether the biomarker effects change over time on repeat dosing and any potential differences observed between single and repeat doses.

Detailed description

This is a two part protocol (Parts A and B) in healthy volunteers evaluating the pharmacokinetics/ pharmacodynamics (PK/PD) of azithromycin to investigate the usefulness of various biomarkers (e.g., IL-10, GM-CSF, MDC, with and without ex vivo lipopolysaccharide (LPS) stimulation) as markers of macrolide anti-inflammatory activity. Part A is a randomized, open-label parallel group study evaluating PK/PD of a single azithromycin dose of 250 or 1000 mg. Data from Part A will be used to assess the dose resulting in induction/inhibition of various ex vivo biomarkers relative to a 250 mg dose of azithromycin (the clinical dose used in treatment of neutrophil-induced inflammatory conditions). This information will guide the range of doses to be studied in a FTIH study of a new chemical entity. Part B is a repeat dose study treating subjects with Azithromycin (250 mg every other day for 3 weeks), the dose approximates that used in the treatment of chronic neutrophil related inflammatory conditions. This information will provide insight into whether the biomarker effects change over time on repeat dosing and any potential differences observed between single and repeat doses.

Conditions

• Autoimmune Diseases

Interventions

Type	Name	Description
DRUG	Azithromycin - 250 mg	Part A - A single azithromycin dose of 250 mg.
DRUG	Azithromycin - 1000 mg	Part A - A single azithromycin dose of 1000 mg.
DRUG	Azithromycin - 250 mg every other day for 3 weeks	Part B - Repeat dose study treating subjects with Azithromycin (250 mg every other day for 3 weeks), the dose approximates that used in the treatment of chronic neutrophil-related inflammatory conditions.

Timeline

• Start date: 2011-03-30
• Primary completion: 2011-05-12
• Completion: 2011-05-12
• First posted: 2011-08-15
• Last updated: 2017-07-21

Locations

1 site across 1 country: United Kingdom