A Single and Repeat Dose PK/PD Study to Characterise Biomarker Response in Healthy Subjects Treated With Azithromycin
Condition: Autoimmune Diseases
MeSH terms: Autoimmune Diseases
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Azithromycin - 250 mg; Azithromycin - 1000 mg; Azithromycin - 250 mg every other day for 3 weeks
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Part A - A single azithromycin dose of 250 mg.; Part A - A single azithromycin dose of 1000 mg.; 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.
Intervention MeSH terms: Azithromycin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science