NCT01416350

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2011

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 30, 2011

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 12, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 12, 2011

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 23, 2011

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 15, 2011

Completed
Last Updated

July 21, 2017

Status Verified

July 1, 2017

Enrollment Period

1 month

First QC Date

June 23, 2011

Last Update Submit

July 18, 2017

Conditions

Autoimmune Diseases

Outcome Measures

Primary Outcomes (2)

  • 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).

    For Part A Day 1 to 15

  • 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

    For Part A Day 1 to 15

Secondary Outcomes (2)

  • Biomarker:Clinical Dose Ratio for each relevant biomarkers

    For Part B Day 1 to 35

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

    For Part B Day 1 to 35

Study Arms (2)

Part A - randomized, open-label parallel group

ACTIVE COMPARATOR

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 mgDrug: Azithromycin - 1000 mg

Part B - repeat dose group

ACTIVE COMPARATOR

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

Azithromycin - 250 mgDRUG

Part A - A single azithromycin dose of 250 mg.

Part A - randomized, open-label parallel group
Azithromycin - 1000 mgDRUG

Part A - A single azithromycin dose of 1000 mg.

Part A - randomized, open-label parallel group
Azithromycin - 250 mg every other day for 3 weeksDRUG

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.

Part B - repeat dose group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2011

First Posted

August 15, 2011

Study Start

March 30, 2011

Primary Completion

May 12, 2011

Study Completion

May 12, 2011

Last Updated

July 21, 2017

Record last verified: 2017-07

Locations

GB(1)