Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis

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

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

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Tedizolid PO; Drug: Tedizolid IV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: May 6, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 21, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Oxazolidinones; Tedizolid
• Other Study ID Numbers: HS-15-00182