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

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

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.

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.

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