Ascending Dose Pharmacokinetic (PK) and Absolute Bioavailability (BA) (IV/SAD/MAD)

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

Status and phase: Completed; Phase 1

Conditions: Bacterial Infections

Treatments: Drug: TR-701 FA for injection, 200 mg/vial; Drug: TR-701 FA tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT00983255

1986-008

TR701-107 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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90 participants in 4 patient groups

SAD/ Part A

Experimental group

Description:

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

Treatment:

Drug: TR-701 FA for injection, 200 mg/vial

MAD / Part B

Experimental group

Description:

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

Treatment:

Drug: TR-701 FA for injection, 200 mg/vial

Bioavailability / Part C

Experimental group

Description:

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.

Treatment:

Drug: TR-701 FA tablets

Drug: TR-701 FA for injection, 200 mg/vial

Venous Tolerability/ Part D

Experimental group

Description:

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

Treatment:

Drug: TR-701 FA for injection, 200 mg/vial