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CompletedNCT01416350Updated Jul 21, 2017

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

A Phase 1 interventional study of Azithromycin - 250 mg and Azithromycin - 1000 mg in Autoimmune Diseases, sponsored by GlaxoSmithKline. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-07-21.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Autoimmune Diseases

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03

In context

Autoimmune Diseases

655 studies on the registry are indexed under Autoimmune Diseases; 275 are open to participants now.

This study's enrollment of 20 is below the median of 40 across 427 interventional studies indexed under Autoimmune Diseases.

Browse Autoimmune Diseases studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Male or female between 18 and 65 years of age inclusive
  • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy
  • Child-bearing potential and agrees to use one of the contraception methods
  • Body weight ≥ 50 kg and body mass index (BMI) within the range 18.5 - 30 kg/m2 (inclusive)
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions
  • Single QT duration corrected for heart rate by Bazett's formula (QTcB) \< 450 msec.

Exclusion criteria

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities
  • A positive pre-study drug/alcohol screen
  • A positive test for HIV antibody
  • History of regular alcohol consumption within 6 months of the study
  • The subject has participated in a clinical trial and has received an investigational product within the 3 months
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements
  • History of sensitivity to any of the study medications, or erythromycin, any macrolide or ketolide antibiotic
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
  • The subject has donated blood in the 3 months prior to the study
  • Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing
  • Lactating females
  • Unwillingness or inability to follow the procedures outlined in the protocol
  • Subject is mentally or legally incapacitated
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Active comparator
    Part A - randomized, open-label parallel group

    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.

    Drug: Azithromycin - 250 mg · Drug: Azithromycin - 1000 mg

  • Active comparator
    Part B - repeat dose group

    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.

    Drug: Azithromycin - 250 mg every other day for 3 weeks

Interventions

  • DrugAzithromycin - 250 mg

    Part A - A single azithromycin dose of 250 mg.

  • DrugAzithromycin - 1000 mg

    Part A - A single azithromycin dose of 1000 mg.

  • DrugAzithromycin - 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.

06

What researchers measure

Primary outcomes

  1. PK/PD modelling of the time course of concentrations and inhibition/induction of relevant biomarkers including the concentration resulting in 50% induction or inhibition (IC50)

    Parameters from PK/PD modelling of the time course of concentrations and inhibition/induction of relevant ex vivo biomarkers (e.g., MDC, GM-CSF and IL-10 with varying levels of LPS stimulation) including the IC50 along with distribution parameters (e.g., kin and kout).

    Time frame: For Part A Day 1 to 15

  2. Maximum inhibition/induction of relevant biomarkers and timing of this maximum

    Maximum inhibition/induction of relevant ex vivo biomarkers (e.g., MDC, GM-CSF and IL-10) and timing of this maximum

    Time frame: For Part A Day 1 to 15

Secondary outcomes

  1. Biomarker:Clinical Dose Ratio for each relevant biomarkers

    Biomarker:Clinical Dose Ratio (dose which would result in maximum observed concentration (Cmax) above the concentration resulting in 80% induction or inhibition (IC80) in ≥75% of patients divided by clinical dose of 250 mg) for each relevant ex vivo biomarkers.

    Time frame: For Part B Day 1 to 35

  2. Observed maximum inhibition/induction and its coefficient of variation (CV)

    For each relevant biomarker, the observed maximum inhibition/induction and its coefficient of variation (CV).

    Time frame: For Part B Day 1 to 35

07

Study locations

1 site
  • GSK Investigational Site
    London, NW10 7EW, United Kingdom
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 21, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01416350
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Aug 15, 2011
Start date
Mar 30, 2011
Primary completion
May 12, 2011
Completion
May 12, 2011
Last update
Jul 21, 2017

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2017. You cannot join it, but the record below documents what was studied.

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