Effect of Linezolid on Ex Vivo Neutrophil and Monocyte Function in Healthy Males

Study Overview
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Brief Summary
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Results from previous studies have been inconclusive and the effect of linezolid on cytokines remains unclear. This study is designed to evaluate the effect of linezolid on the functionality of white blood cells (neutrophils and monocytes) in healthy subjects.

Official Title
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An Open-label, Placebo-controlled Phase 1 Study to Evaluate the Effect of Linezolid on Ex Vivo Neutrophil and Monocyte Function in Healthy Male Subjects

Conditions
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Gram Positive Infection

Intervention / Treatment
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* Drug: linezolid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between the ages of 20 and 45 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement and clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Exclusion Criteria: Any condition possibly affecting drug absorption (eg, gastrectomy). Subject who had a bacterial/viral infection within 2 weeks prior to the first dose of study medication. Subjects with current or prior neutropenia (eg, <1.4 x 109 neutrophils /L).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br> | Drug: linezolid<br>* 600 mg oral tablet twice daily for 4.5 days<br>* Other names: Zyvox;|
| Placebo Comparator: Arm B<br> | Drug: Placebo<br>* 500 mg oral placebo twice daily for 4.5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in phagocytosis of gram-negative bacteria by neutrophils |  | Baseline, day 4 and day 5 | 
| Change from baseline in phagocytosis of gram-negative bacteria by monocytes |  | Baseline, day 4 and day 5 | 
| Change from baseline in interleukin-1 receptor antagonist secretion in response to lipopolysaccharide stimulation |  | Baseline, day 4 and day 5 | 
| Change from baseline in interleukin-1-beta secretion in response to lipopolysaccharide stimulation |  | Baseline, day 4 and day 5 | 
| Change from baseline in interleukin-6 secretion in response to lipopolysaccharide stimulation |  | Baseline, day 4 and day 5 | 
| Change from baseline in interleukin-8 secretion in response to lipopolysaccharide stimulation |  | Baseline, day 4 and day 5 | 
| Change from baseline in tumor necrosis factor alpha secretion in response to lipopolysaccharide stimulation |  | Baseline, day 4 and day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linezolid peak concentration on day 4 |  | day 4 | 
| Linezolid peak concentration on day 5 |  | day 5 | 
| Linezolid trough concentration on day 5 |  | day 5 |