1371. Safety, Tolerability and Pharmacokinetics of Multiple Doses of TP-6076, a Novel, Fully Synthetic Tetracycline, in a Phase 1 Study
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall

Background:  TP-6076 is a novel, fully synthetic tetracycline being developed for the treatment of serious bacterial infections including those caused by multidrug-resistant Acinetobacter baumannii. TP-6076 has demonstrated potent activity in vitro against carbapenem-resistant strains of A. baumannii, with MIC90 64 times lower compared to tigecycline and 256 times lower compared to minocycline. We now report the results of a multiple ascending dose study in normal healthy volunteers.

Methods:  This was a phase 1, single site, randomized, double-blind, placebo-controlled dose-escalating, multiple dose study in healthy adults who met the inclusion/exclusion criteria and provided informed consent prior to any study procedure. Cohorts of 8 subjects each (6 active and 2 placebo) received daily doses of 6.0 to 40.0 mg TP-6076 or placebo for 7 days.  Plasma and urine samples for pharmacokinetic (PK) analyses were collected starting immediately prior to dosing until 96 hours after the last dose.  Safety was assessed through collection of adverse events (AEs), clinical laboratories, vital signs, ECG and physical exam data.

Results: The geometric mean derived PK parameters for TP-6076 were:

TP-6076 Dose (mg)

AUC0-tau (ng*h/mL)

T1/2 (h)

 

Day 1

Day 7

Day 7

6.0

1043

1621

21.2

20.0

4871

7139

27.7

30.0

6382

10149

28.4

35.0

7842

10825

28.8

40.0

9433

12698

25.8

There were no serious or severe AEs reported. The most frequently reported AEs were gastrointestinal events, including nausea and vomiting, and localized infusion site reactions. There were no clinically significant changes in clinical laboratory values, ECG parameters or physical exam findings.

Conclusion:   Following multiple IV doses of TP-6076, plasma exposure increased as dose increased.  Multiple IV doses of TP-6076 were generally well tolerated, with higher gastrointestinal adverse event rates in the higher dose groups.  

Larry Tsai, MD and Alison Moore, BS, Tetraphase Pharmaceuticals, Watertown, MA

Disclosures:

L. Tsai, Tetraphase Pharmaceuticals: Employee and Shareholder , Salary .

A. Moore, Tetraphase Pharmaceuticals: Employee , Salary .

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