Single Dose PK of IV Tedizolid Phosphate in Morbidly Obese and Non-Obese Adults

Phase 4

Completed

Conditions: Obesity

Interventions: Drug: Tedizolid phosphate

Registration Number: NCT02342418

Lead Sponsor: Amit.Pai

Brief Summary: This is an open label, single-dose, pharmacokinetic study in 9 obese and 9 age-, sex-, ideal body weight- matched non-obese subjects. Qualifying subjects who have completed an informed consent will receive a single intravenous dose of tedizolid with the collection of 11 blood samples over 72 hours post dose.

Detailed Description: Subjects will present to the clinical research unit in the morning (approximately 6:30 a.m.) of the dosing day. A urine pregnancy test will be performed to rule out pregnancy prior to administration of the tedizolid phosphate dose to female subjects. The subject's height, total body weight, and vital signs (heart rate, blood pressure, temperature, and respiratory rate) will be recorded. Subjects judged (by study physician) to be healthy enough to participate will proceed with the study procedures.

An 18-20 gauge intravenous peripheral catheter will be inserted into the antecubital vein or a vein in the fore-arm of the non-dominant arm for sequential blood sampling, and an initial predose blood sample (5 mL) will be collected. A minimum of 3-5 mL of blood is required per pharmacokinetic sampling time-point. Each blood collection tube will be pre-labeled with: 1.) study protocol number; 2.) subject study number; 3.) date of collection; 4.) time-point. A 0.9% Sodium Chloride infusion may be run through the peripheral line at 30 to 40 mL per hour to maintain catheter patency for the 12 hour sampling phase. Alternatively, a heparin lock technique will be utilized to maintain intravascular catheter patency.

A single-dose of tedizolid phosphate will be administered as an intravenous infusion (250 mL normal saline) over 1 hour (\~8:00 a.m.). The intravenous administration tubing will be flushed with 0.9% Sodium Chloride infusion at 250 mL per hour (to match the tedizolid phosphate rate of infusion) for 10 minutes to ensure complete dose delivery. Blood samples (5 mL) will be collected 0.5 (middle of infusion), 1 (end of infusion), 2, 4, 6, 8, 12, 24, 48, and 72 hours post dose in blood collection tubes. The plasma will be harvested (centrifugation at 4°C) within 60 minutes of collection and stored at -70°C as two aliquots until analysis. The intravascular catheter "dead-space" volume will be discarded prior to blood sample collection by withdrawing 1.5-2 mL from the catheter to ensure no unintentional sample dilution. The intravascular catheter will be removed after the 12 hour sample and the subject will be discharged from the research unit. The subject will return to the research unit for blood sample collection on a daily basis at the following points: 24 (Visit 3), 48 (Visit 4), and 72 hours (Visit 5) after the dose via a peripheral vein needle stick. The exact date and time of blood sample collection will be recorded on case report forms. Each blood sample tube will be inverted and made up-right 5 times to afford mixing of blood with the anticoagulant. Blood samples will be maintained on wet ice and centrifuged at 1200 g for 10 minutes at 4°C within 60 minutes of collection to yield approximately 2 mL of plasma per 5 mL blood collection. The plasma samples will be transferred from the -20°C freezer for storage at -70°C at the end of the sample collection period until analysis.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Non-smoking or light-smoking (≤ 5 cigarettes per day) volunteers
Estimated CLcr (Cockcroft-Gault equation) ≥ 90 mL/min
Female subjects of childbearing potential (CBP) either surgically sterilized, using hormonal contraceptives or an effective barrier method of contraception (diaphragm, cervical cap, condom) or agree to abstain from sex from the time of pre-study screening, during the entire study period and 4 weeks following the study period
Platelets count ≥ 140,000/mL
Absolute neutrophil count (ANC) ≥ 1800/mL

Exclusion Criteria

History of hypersensitivity reaction to any oxazolidinone
BMI < 18.5 kg/m2
Any chronic medical condition requiring pharmacologic therapy
Transaminases (AST or ALT) > 2.5 x upper limit of normal
Total bilirubin > 1.5 x upper limit of normal
Positive urine pregnancy test (if female)
Abnormal electrocardiogram (ECG) as judged by the study physician
Unable to tolerate venipuncture and multiple blood draws
Clinically significant abnormal physical examination defined as a physical finding requiring further clinical work-up
Unable to independently provide a written informed consent

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Morbidly obese	Tedizolid phosphate	The morbidly obese (BMI ≥ 40 kg/m2) arm will be recruited first. Each morbidly obese subject will be matched to a non-obese subject (BMI 18.5-29.9 kg/m2) based on age (± 5 years), sex, and ideal body weight (± 4.6 kg, i.e. ± 5 cm in height). Each group will receive a single dose of tedizolid phosphate 200 mg through a peripheral intravenous catheter.
Non-obese	Tedizolid phosphate	Each non-obese subject will be matched to a morbidly obese subject (BMI 18.5-29.9 kg/m2) based on age (± 5 years), sex, and ideal body weight (± 4.6 kg, i.e. ± 5 cm in height). Each group will receive a single dose of tedizolid phosphate 200 mg through a peripheral intravenous catheter.

Primary Outcome Measures

Name	Time	Method
This Outcome Measure is the Tedizolid Area Under the Concentration Time-curve From Time 0 to 72 Hours in Morbidly Obese Subjects and Matched Non-obese Subjects.	12 months	The area under the concentration-time curve is measured in units of mg of tedizolid per liter of plasma multiplied by time in hours (hour\*mg/L) from time 0 to 72 hours. This comparison was made between the two groups of subjects that included morbidly obese subjects to matched non-obese subjects.

Secondary Outcome Measures

Name	Time	Method
This Outcome Measure is the Maximum Plasma Concentration of Tedizolid in Morbidly Obese Subjects Compared to Nonobese Subjects	12 months	The maximum concentration or Cmax value is measured in units of milligrams of tedizolid per liter of plasma.This comparison was made between the two groups of subjects that included morbidly obese subjects to matched non-obese subjects.