Program Schedule

263
Gastrointestinal Safety Profile of Tedizolid: Pooled Results from Two Phase 3 Trials in Acute Bacterial Skin and Skin Structure Infections

Session: Poster Abstract Session: Antimicrobial Resistance: Novel Agents and Approaches to Gram-positive Infections
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC

Background: Tedizolid (TZD) is a novel oxazolidinone antibacterial with potent activity against a wide range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and it has a favorable safety profile. Two Phase 3 clinical trials demonstrated the noninferiority of 6 days of TZD 200 mg once daily compared with 10 days of linezolid (LZD) 600 mg twice daily for treatment of acute bacterial skin and skin structure infections.

Methods: Pooled data from 1324 patients (TZD, N=662; LZD, N=662) were used to compare the gastrointestinal (GI) adverse event (AE) profiles of TZD and LZD.

Results: GI disorders were the most common AEs and were reported less frequently in the TZD (16.0%) than the LZD group (23.0%); the most common AEs within this system organ class were nausea, diarrhea, and vomiting (Figure 1). The first episodes of these GI AEs occurred primarily within the first 6 days of treatment. The lower incidence of GI AEs in the TZD group was noted during this early period, when both groups were receiving active drug (Table 1). Discontinuation of study drug due to GI AEs was reported for 3 patients receiving TZD (abdominal discomfort, diarrhea, and vomiting, in 1 patient each) and for 6 receiving LZD (vomiting and nausea in 3 patients each). 

Conclusion: Treatment with TZD 200 mg once daily for 6 days was associated with an improved GI AE profile compared with LZD 600 mg twice daily for 10 days. Most of the GI AEs occurred during the first 6 days of the study period while patients in both treatment arms were exposed to active study drug, suggesting that the difference in GI AEs may reflect a pharmacologic difference between TZD and LZD rather than a difference in duration of exposure.

 

 

Figure 1. Incidence of gastrointestinal adverse events 

Table 1. Onset of First Episode of Gastrointestinal Adverse Events

 

 

AE

 

 

Time of Onset

TZD 200 mg once daily for 6 days (N=662)

n (%)

LZD 600 mg twice daily for 10 days (N=662)

n (%)

GI disorders overall

0-6 days

86 (13.0)

125 (18.9)

 

7-10 days

10 (1.5)

19 (2.9)

 

>10 days

10 (1.5)

8 (1.2)

Diarrhea

0-6 days

19 (2.9)

27 (4.1)

 

7-10 days

5 (0.8)

7 (1.1)

 

>10 days

2 (0.3)

1 (0.2)

Nausea

0-6 days

47 (7.1)

70 (10.6)

 

7-10 days

3 (0.5)

8 (1.2)

 

>10 days

4 (0.6)

3 (0.5)

Vomiting

0-6 days

13 (2.0)

31 (4.7)

 

7-10 days

3 (0.5)

2 (0.3)

 

>10 days

3 (0.5)

4 (0.6)

 

Edward Fang, Carisa De Anda, Sonia Minassian, Shawn Flanagan and Philippe Prokocimer, Cubist, San Diego, CA

Disclosures:

E. Fang, Trius/Cubist: Employee, Salary

C. De Anda, Cubit: Employee and Shareholder, Salary

S. Minassian, Cubist: Consultant, Consulting fee

S. Flanagan, Cubist: Employee and Shareholder, Salary

P. Prokocimer, Cubist: Employee and Shareholder, Salary

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