Bacterial Infections
Conditions
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.
Interventions
DRUGTR-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
DRUGTR-701 FA tablets
TR-701 FA will be given once orally as a 200 mg tablet in Part C.
Sponsors
Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Assessments | 10 days |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the pharmacokinetics of TR-701 and its microbiologically active moiety TR-700 after single and multiple IV doses of TR-701 FA | 10 days |
| To determine the absolute bioavailability of oral TR-701 FA following single oral and IV dose administrations in healthy adult subjects | 4 days |
Countries
United States
Outcome results
None listed