AzTrials
AzTrials

Autoimmune DiseasesPhase 1NCT01416350

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

A Phase 1 study testing Azithromycin - 250 mg, Azithromycin - 1000 mg and Azithromycin - 250 mg every other day for 3 weeks in people with Autoimmune Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Autoimmune Diseases
What is being tested?
Azithromycin - 250 mg, Azithromycin - 1000 mg and Azithromycin - 250 mg every other day for 3 weeks
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited Kingdom
Study dates
30 Mar 2011to 12 May 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    London, NW10 7EW

Other trials in United Kingdom

About this study

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

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.

Being tested
Azithromycin - 250 mg, Azithromycin - 1000 mg, Azithromycin - 250 mg every other day for 3 weeks
Medical subject headings
Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azithromycin - 250 mgDrug

    Part A - A single azithromycin dose of 250 mg.

  • Azithromycin - 1000 mgDrug

    Part A - A single azithromycin dose of 1000 mg.

  • 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.

Study groups in NCT01416350
Study groupRoleWhat they receive
Part A - randomized, open-label parallel groupActive comparatorPart 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.
Receives: Drug: Azithromycin - 250 mg; Drug: Azithromycin - 1000 mg
Part B - repeat dose groupActive comparatorPart 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.
Receives: Drug: Azithromycin - 250 mg every other day for 3 weeks

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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

    Measured: For Part A Day 1 to 15

Secondary outcomes (2)

  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.

    Measured: 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).

    Measured: For Part B Day 1 to 35

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2011 (estimated)
  2. Study start30 Mar 2011
  3. Primary completion12 May 2011
  4. Study completion12 May 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01416350
Sponsor's protocol ID
115360
Status last verified
Jul 2017
First submitted
23 Jun 2011
Last updated
21 Jul 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azithromycin - 250 mg, Azithromycin - 1000 mg and Azithromycin - 250 mg every other day for 3 weeks in people with Autoimmune Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: For Part A Day 1 to 15). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01416350.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2017.

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