Ascending Dose Pharmacokinetic (PK) and Absolute Bioavailability (BA)

NCT ID: NCT00983255

Last Updated: 2016-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-01-31

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.

Conditions

Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

SAD/ Part A

Single IV infusions of placebo or TR-701 FA given at 50, 100, 200, and 400 mg.

Group Type: EXPERIMENTAL

TR-701 FA for injection, 200 mg/vial

Intervention Type: DRUG

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

MAD / Part B

Multiple IV infusion of placebo or TR-701 FA given daily for 7 days at 200 and 400 mg.

Group Type: EXPERIMENTAL

TR-701 FA for injection, 200 mg/vial

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

TR-701 FA for injection, 200 mg/vial

Intervention Type: DRUG

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

TR-701 FA tablets

Intervention Type: DRUG

TR-701 FA will be given once orally as a 200 mg tablet in Part C.

Venous Tolerability/ Part D

IV infusions of placebo and 200 mg TR-701 FA given daily for 3 days,

Group Type: EXPERIMENTAL

TR-701 FA for injection, 200 mg/vial

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

TR-701 FA tablets

TR-701 FA will be given once orally as a 200 mg tablet in Part C.

Intervention Type: DRUG

Other Intervention Names

Torezolid Phospate; Torezolid Phosphate Tablet

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas Siebers, MD

Role: PRINCIPAL_INVESTIGATOR

Covance Clinical Research Unit, Madison, WI, USA

Locations

Covance Clinical Research Unit

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24989138 (View on PubMed)

Other Identifiers

TR701-107

Identifier Type: OTHER

Identifier Source: secondary_id

1986-008

Identifier Type: -

Identifier Source: org_study_id