Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis

Study Overview
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Brief Summary
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The proposed study is designed to characterize the pharmacokinetics of intravenous and oral tedizolid in patients with Cystic Fibrosis.

Detailed Description
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Recent epidemiological studies have demonstrated that the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the airways of patients with CF is associated with more rapid lung function decline and a higher mortality. Tedizolid is a new antibiotic with potent activity against MRSA. Tedizolid is currently FDA approved for treatment of skin soft tissue infections with MRSA. The proposed study is designed to characterize the pharmacokinetics of intravenous and oral tedizolid in patients with CF.

Official Title
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Steady-State Pharmacokinetics of Tedizolid in Plasma and Sputum of Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Tedizolid PO
* Drug: Tedizolid IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CF based on positive sweat chloride or known CF mutation Age > 17 years Able to spontaneously expectorate sputum Exclusion Criteria: Any clinically significant laboratory abnormalities Presence of an ongoing acute pulmonary exacerbation Pregnancy Serious past allergy to linezolid or tedizolid No alcohol, nicotine, or caffeine-containing products during the study period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tedizolid PO<br>Tedizolid phophate 200mg tablet | Drug: Tedizolid PO<br>* Participants will be randomized to receive tedizolid oral 200mg once daily for 3 days and crossed over to IV after a 1 week washout.<br>|
| Experimental: Tedizolid IV<br>Tedizolid phophate 200mg IV | Drug: Tedizolid IV<br>* Participants will be randomized to receive tedizolid IV 200mg once daily for 3 days and crossed over to PO after a 1 week washout.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Cmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose | 2 days | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) | Area under the curve was calculated using samples collected at baseline (0 h) , 0.5, 1, 2, 3, 4, 8, 24, and 48 hours post-dose and using the equation AUC=Dose*F/CL | 2 days | 
| Time to Peak Plasma Concentration (Tmax) | Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose | 2 days | 
| Peak Sputum Concentration | Peak sputum concentration was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose. | 2 days | 
| Area Under the Sputum Concentration Versus Time Curve (AUC) | AUC was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose | 2 days | 
| Time to Peak Sputum Concentration (Tmax) | Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose. Tmax was derived from pooled sputum data due to sparse samples and therefore do not have standard deviations. | 2 days |