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

Phase 1

Completed

• Conditions: Bacterial Infections
• Interventions: Drug: TR-701 FA for injection, 200 mg/vial; Drug: TR-701 FA tablets

• Registration Number: NCT00983255
• Lead Sponsor: Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

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.

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-22
• Study First Submitted QC: 2009-09-23
• Study First Posted: 2009-09-24
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-18
• Last Update Posted: 2016-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
SAD/ Part A	TR-701 FA for injection, 200 mg/vial	Single IV infusions of placebo or TR-701 FA given at 50, 100, 200, and 400 mg.
MAD / Part B	TR-701 FA for injection, 200 mg/vial	Multiple IV infusion of placebo or TR-701 FA given daily for 7 days at 200 and 400 mg.
Bioavailability / Part C	TR-701 FA for injection, 200 mg/vial	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.
Bioavailability / Part C	TR-701 FA tablets	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.
Venous Tolerability/ Part D	TR-701 FA for injection, 200 mg/vial	IV infusions of placebo and 200 mg TR-701 FA given daily for 3 days,

Primary Outcome Measures

Name	Time	Method
Safety Assessments	10 days

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Covance Clinical Research Unit; 🇺🇸 Madison, Wisconsin, United States