Clinical trial NCT00983255: Ascending Dose Pharmacokinetic (PK) and Absolute Bioavailability (BA)
Official title: A Double-Blind, Placebo-Controlled, Single & Multiple Ascending Dose, Safety, Tolerability, & PK Study of an IV Form of TR-701 Free Acid & an Open-Label, Crossover Absolute BA Determination of a TR-701 FA Tablet in Normal Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacterial Infections
Lead sponsor: Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2009-09-24
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of single rising and multiple rising IV doses of TR-701 FA and to determine the absolute bioavailability of oral TR-701 FA following single oral and IV dose administrations in healthy adult subjects.

Detailed description: SAD/Part A.

* All subjects in the Pilot Cohort will receive a single infusion of 50 mg TR-701 FA for injection in 250 cc of saline over 180 minutes.
* Subjects in Cohort 1 will be randomized to receive a single infusion of placebo or 100 mg of TR-701 FA for injection in 250 or 500 cc of saline over 60 or 120 minutes.
* Subjects in Cohort 2 will be randomized to receive a single infusion of placebo or 200 mg of TR-701 FA for injection in 250 or 500 cc of saline over 60 or 120 minutes.
* Subjects in Cohort 3 will be randomized to receive a single infusion of placebo or 400 mg of TR-701 FA for injection in 250 or 500 cc of saline over 60 or 120 minutes.

MAD/Part B

* Subjects in Cohort 4 will be randomized to receive once daily infusions of placebo or 200 mg of TR-701 FA for injection in 250 cc of saline over 60 minutes for 7 days.
* Subjects in Cohort 5 will be randomized to receive once daily infusions of placebo or 300 mg of TR-701 FA for injection in 250 cc of saline over 60 minutes for 7 days.

BA/Part C

* Subjects in Cohort 6 will receive a single 60 minute infusion of 200 mg TR-701 FA for injection in 250 cc of saline and a singe oral dose of 200 mg TR-701 FA tablet in an open-label crossover design.

Venous Tolerability/Part D

- Subjects in Cohort 8 will receive once daily 60 minute infusions of 200 mg TR-701 FA for injection in 250 cc of saline for 3 days and once daily placebo infusions for 3 daysin a blinded crossover design.

Eligibility criteria: Inclusion Criteria:

* in good health
* body mass index of 20 to 29.9 kg/m2
* female subjects must be post menopausal for at least 1 year, surgically sterile, abstinent or agree to use an effective method of birth control

Exclusion Criteria:

* history or clinical manifestation of any clinically significant disorder
* history of hypersensitivity to any drug compound
* history of stomach or intestinal surgery or resection
* history of infections of unexplained frequency or severity
* history of alcoholism or drug addiction within 1 year
* use of any tobacco- or nicotine-containing products within 6 months
* use of alcohol-, grapefruit-, caffeine-, or high tyramine-containing foods or beverages
* use of any other medications
* pregnancy, lactation, or breastfeeding

Primary outcomes:
measure: Safety Assessments
timeFrame: 10 days
Secondary outcomes:
measure: To evaluate the pharmacokinetics of TR-701 and its microbiologically active moiety TR-700 after single and multiple IV doses of TR-701 FA
timeFrame: 10 days
measure: To determine the absolute bioavailability of oral TR-701 FA following single oral and IV dose administrations in healthy adult subjects
timeFrame: 4 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Covance Clinical Research Unit, Madison, WI, USA
name: Nicholas Siebers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flanagan S, Fang E, Munoz KA, Minassian SL, Prokocimer PG. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy. 2014 Sep;34(9):891-900. doi: 10.1002/phar.1458. Epub 2014 Jul 3.