Single and Multiple Ascending Dose Pharmacokinetic (PK) Study of Intravenous (IV) TR-701 Free Acid (FA) and an Absolute Bioavailability (BA) Study of TR-701 FA Tablets in Healthy Adults - Full Text View

Purpose

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.

Condition	Intervention	Phase
Bacterial Infections	Drug: TR-701 FA for injection, 200 mg/vial Drug: TR-701 FA tablets	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
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

Resource links provided by NLM:

MedlinePlus related topics: Bacterial Infections

U.S. FDA Resources

Further study details as provided by Trius Therapeutics, Inc.:

Primary Outcome Measures:

Safety Assessments [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the pharmacokinetics of TR-701 and its microbiologically active moiety TR-700 after single and multiple IV doses of TR-701 FA [ Time Frame: 10 days ] [ Designated as safety issue: No ]
To determine the absolute bioavailability of oral TR-701 FA following single oral and IV dose administrations in healthy adult subjects [ Time Frame: 4 days ] [ Designated as safety issue: No ]

Enrollment:	90
Study Start Date:	September 2009
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: SAD/ Part A Single IV infusions of placebo or TR-701 FA given at 50, 100, 200, and 400 mg.	Drug: TR-701 FA for injection, 200 mg/vial TR-701 FA for injection will be given as a single infusion at doses of 50 mg, 100 mg, 200 mg, and 400 mg in SAD/Part A (Pilot and Cohorts 1 to 3). TR-701 FA for injection will be given as once daily infusions at doses of 200 mg and 400 mg for 7 days in MAD/Part B (Cohorts 4 & 5). TR-701 FA for injection will be given once as a 200 mg IV infusion in BA/Part C (Cohort 6). TR-701 FA 200 mg will be given daily for 3 days in Venous Tolerability/Part D Other Name: Torezolid Phospate
Experimental: MAD / Part B Multiple IV infusion of placebo or TR-701 FA given daily for 7 days at 200 and 400 mg.	Drug: TR-701 FA for injection, 200 mg/vial TR-701 FA for injection will be given as a single infusion at doses of 50 mg, 100 mg, 200 mg, and 400 mg in SAD/Part A (Pilot and Cohorts 1 to 3). TR-701 FA for injection will be given as once daily infusions at doses of 200 mg and 400 mg for 7 days in MAD/Part B (Cohorts 4 & 5). TR-701 FA for injection will be given once as a 200 mg IV infusion in BA/Part C (Cohort 6). TR-701 FA 200 mg will be given daily for 3 days in Venous Tolerability/Part D Other Name: Torezolid Phospate
Experimental: Bioavailability / Part C TR-701 FA tablet given once orally as a 200 mg tablet or TR-701 FA for injection given once as a 200 mg IV infusion.	Drug: TR-701 FA for injection, 200 mg/vial TR-701 FA for injection will be given as a single infusion at doses of 50 mg, 100 mg, 200 mg, and 400 mg in SAD/Part A (Pilot and Cohorts 1 to 3). TR-701 FA for injection will be given as once daily infusions at doses of 200 mg and 400 mg for 7 days in MAD/Part B (Cohorts 4 & 5). TR-701 FA for injection will be given once as a 200 mg IV infusion in BA/Part C (Cohort 6). TR-701 FA 200 mg will be given daily for 3 days in Venous Tolerability/Part D Other Name: Torezolid Phospate Drug: TR-701 FA tablets TR-701 FA will be given once orally as a 200 mg tablet in Part C. Other Name: Torezolid Phosphate Tablet
Experimental: Venous Tolerability/ Part D IV infusions of placebo and 200 mg TR-701 FA given daily for 3 days,	Drug: TR-701 FA for injection, 200 mg/vial TR-701 FA for injection will be given as a single infusion at doses of 50 mg, 100 mg, 200 mg, and 400 mg in SAD/Part A (Pilot and Cohorts 1 to 3). TR-701 FA for injection will be given as once daily infusions at doses of 200 mg and 400 mg for 7 days in MAD/Part B (Cohorts 4 & 5). TR-701 FA for injection will be given once as a 200 mg IV infusion in BA/Part C (Cohort 6). TR-701 FA 200 mg will be given daily for 3 days in Venous Tolerability/Part D Other Name: Torezolid Phospate

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

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00983255

Locations

United States, Wisconsin
Covance Clinical Research Unit
Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

Trius Therapeutics, Inc.

Investigators

Principal Investigator:

Nicholas Siebers, MD

Covance Clinical Research Unit, Madison, WI, USA

More Information

No publications provided

Responsible Party:	Paul Bien, Senior Director Clinical Operations/Project Management, Trius Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00983255 History of Changes
Other Study ID Numbers:	TR701-107
Study First Received:	September 22, 2009
Last Updated:	July 26, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Bacterial Infections

ClinicalTrials.gov processed this record on May 23, 2013

Single and Multiple Ascending Dose Pharmacokinetic (PK) Study of Intravenous (IV) TR-701 Free Acid (FA) and an Absolute Bioavailability (BA) Study of TR-701 FA Tablets in Healthy Adults (IV/SAD/MAD)