Last updated: 11/07/2018 09:24:51
A Single and Repeat Dose PK/PD Study to Characterise Biomarker Response in Healthy Subjects Treated with Azithromycin
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Single and Repeat Dose pharmacokinetics/ pharmacodynamics (PK/PD) Study to Characterise theBiomarker Response in Healthy Subjects Treated with the AntiinflammatoryMacrolide Azithromycin
Trial 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., 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 doseof 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 thebiomarker effects change over time on repeat dosing and any potential differences observed between single and repeat doses.
Primary purpose:
Basic Science
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
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)
Timeframe: For Part A Day 1 to 15
Maximum inhibition/induction of relevant biomarkers and timing of this maximum
Timeframe: For Part A Day 1 to 15
Secondary outcomes:
Biomarker:Clinical Dose Ratio for each relevant biomarkers
Timeframe: For Part B Day 1 to 35
Observed maximum inhibition/induction and its coefficient of variation (CV)
Timeframe: For Part B Day 1 to 35
Interventions:
Enrollment:
20
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Sampson MR, Dumitrescu TP, Brouwer KLR, Schmith VD.Population Pharmacokinetics of Azithromycin in Blood, Peripheral Blood Mononuclear Cells, and Polymorphonuclear Cells in Healthy Adults.CPT Pharmacometrics Syst Pharmacol.2014;3(3):1-7
Medical condition
Autoimmune Diseases
Product
Not applicable
Collaborators
Not applicable
Study date(s)
March 2011 to May 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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
- 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
Inclusion and exclusion criteria
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:
- 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
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-12-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 115360 can be found on the GSK Clinical Study Register.
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