TR-701 FA vs Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections

• Sponsor: Trius Therapeutics LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01421511
• Collaborator: (none)
• Enrollment: 666
• Locations: 118
• Arms: 2
• Actual Duration (Months): 15.9
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, double-dummy, multicenter, global Phase 3 study of IV to oral TR-701 FA 200 mg once daily for 6 days versus IV to oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Patients are to start treatment with at least 2 IV doses and may receive IV therapy for the entire treatment duration.

Approximately 100 to 140 sites globally will participate in this study. Patients with an ABSSSI caused by suspected or documented gram positive pathogen(s) at baseline will be randomized 1:1 to study treatment.

Condition or Disease	Intervention/Treatment	Phase
Skin and Subcutaneous Tissue Bacterial Infections	Drug: TR-701 FA; Drug: Linezolid	Phase 3

Detailed Description

The primary objective is to determine the noninferiority (NI) in the early clinical response rate of intravenous (IV) to oral 6 day TR-701 free acid (FA) compared with that of IV to oral 10-day linezolid treatment at 48-72 hours after the first infusion of study drug in the intent-to-treat (ITT) analysis set in patients with acute bacterial skin and skin structure infections (ABSSSI).

Study Design

• Study Type: Interventional
• Actual Enrollment: 666 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of IV to Oral 6-Day TR-701 Free Acid and IV to Oral 10-Day Linezolid for the Treatment of ABSSSI
• Actual Study Start Date: Sep 15, 2011
• Actual Primary Completion Date: Jan 10, 2013
• Actual Study Completion Date: Jan 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TR-701 FA • TR-701 FA IV followed by TR-701 FA tablets	Drug: TR-701 FA; TR-701 FA 200 mg once daily in 250 mL sterile saline for injection as a 60 minute IV infusion TR-701 FA Tablets, 200 mg, orally once daily
Active Comparator: Linezolid • Linezolid IV followed by Linezolid Tablets	Drug: Linezolid; Linezolid 600 mg IV Injection twice daily in 300 mL sterile saline for injection as a 60 minute IV infusion Linezolid Tablets, 600 mg, orally every 12 hours

Outcome Measures

Primary Outcome Measures

1. The Early Clinical Response Rate [48-72 hours]

   Responder: No increase in lesion surface area from baseline.

Secondary Outcome Measures

1. Clinical Response at the End of Therapy Visit [Day 11]

   Responder: No increase in lesion surface area from baseline.

2. Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set [End of Therapy Day 11]

   Responder: No increase in lesion surface area from baseline.

3. Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit [Post-Treatment Evaluation (7-14 days after the End of Therapy)]

   Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, and no further antibiotic therapy required for treatment of primary ABSSSI lesion.

4. Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set. [Post-Treatment Evaluation (7-14 days after the End of Therapy)]

   Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, no new signs, symptoms or complications attributable to the ABSSSI and no further antibiotic therapy required for treatment of primary ABSSSI lesion.

5. Investigator's Assessment of Clinical Response at the 48-72 Hour Visit [48-72 Hours]

   Clinical improvement defined as improvement in overall clinical status.

6. Investigator's Assessment of Clinical Response at the Day-7 Visit [Day 7]

   Clinical improvement defined as improvement in overall clinical status.

7. Change From Baseline in Patient-reported Pain, by Study Visit [Multiple]

   0=no pain, 10=worst pain Only 1 visit per participant for Day 4-6, only 1 visit for Day 7-9, and only 1 visit for Day 10-13.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients requiring IV antibiotic therapy and with systemic signs of infection diagnosed with ABSSSI.

• Diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections

Exclusion Criteria:

• Uncomplicated skin infections

• Severe sepsis or septic shock

• ABSSSI solely due to gram-negative pathogens

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Trius investigator site 159	Dothan	Alabama	United States	36305
2	Trius investigator site 103	Chula Vista	California	United States	91911
3	Trius investigator site 143	Escondido	California	United States	92025
4	Trius investigator site 105	La Mesa	California	United States	91942
5	Trius investigator site 106	Long Beach	California	United States	90813
6	Trius investigator site 157	Long Beach	California	United States	90813
7	Trius investigator site 142	National City	California	United States	91950
8	Trius investigator site 170	San Diego	California	United States	92123
9	Trius investigator site 167	Santa Ana	California	United States	92701
10	Trius investigator site 168	Stockton	California	United States	95204
11	Trius investigator site 141	Sylmar	California	United States	91342
12	Trius investigator site 139	Denver	Colorado	United States	80218
13	Trius investigator site 137	Newark	Delaware	United States	19718
14	Trius investigator site 166	Edgewater	Florida	United States	32132
15	Trius investigator site 101	Columbus	Georgia	United States	31904
16	Trius investigator site 138	Carmel	Indiana	United States	46032
17	Trius investigator site 144	Owensboro	Kentucky	United States	42303
18	Trius investigator site 150	Baton Rouge	Louisiana	United States	70809
19	Trius investigator site 165	Eunice	Louisiana	United States	70535
20	Trius investigator site 154	Boston	Massachusetts	United States	02115
21	Trius investigator site 146	Springfield	Massachusetts	United States	01199
22	Trius investigator site 136	West Roxbury	Massachusetts	United States	02132
23	Trius investigator site 163	Royal Oak	Michigan	United States	48073
24	Trius investigator site 153	Minneapolis	Minnesota	United States	55415
25	Trius investigator site 149	Picayune	Mississippi	United States	39466
26	Trius investigator site 164	Creve Coeur	Missouri	United States	63141
27	Trius investigator site 160	Las Vegas	Nevada	United States	89169
28	Trius investigator site 147	Teaneck	New Jersey	United States	07666
29	Trius investigator site 140	Columbus	Ohio	United States	43215
30	Trius investigator site 162	Lima	Ohio	United States	45801
31	Trius investigator site 161	Rapid City	South Dakota	United States	57702
32	Trius investigator site 155	Franklin	Tennessee	United States	37064
33	Trius investigator site 145	Memphis	Tennessee	United States	38104
34	Trius investigator site 169	Smyrna	Tennessee	United States	37167
35	Trius investigator site 148	Houston	Texas	United States	77030
36	Trius investigator site 352	Cludadela	Buenos Aires	Argentina	B1702FWM
37	Trius investigator site 354	General Roriquez	Buenos Aires	Argentina	B1748
38	Trius investigator site 350	La Plata	Buenos Aires	Argentina	B1900AXI
39	Trius investigator site 350	La Plata	Buenos Aires	Argentina
40	Trius investigator site 353	Lujan	Buenos Aires	Argentina	B6700AOJ
41	Trius investigator site 354	Buenos Aires		Argentina
42	Trius investigator site 355	Buenos Aires		Argentina
43	Trius investigator site 351	Cludad Autonoma De Buenos Aires		Argentina	C1155AHD
44	Trius investigator site 358	La Plata		Argentina
45	Trius investigator site 357	Mar del Plata		Argentina
46	Trius investigator site 359	Paraná, Entre Rios		Argentina
47	Trius investigator site 356	Rosario		Argentina
48	Trius investigator 500	Cairns	Queensland	Australia	4870
49	Trius investigator 501	Herston	Queensland	Australia	4029
50	Trius investigator 503	Nambour	Queensland	Australia	4560
51	Trius investigator 506	Southport	Queensland	Australia	4215
52	Trius investigator 502	Woolloongabba	Queensland	Australia	4102
53	Trius investigator 504	Woolloongabba	Queensland	Australia	4102
54	Trius investigator 505	Richmond	Victoria	Australia	2131
55	Trius investigator site 362	Belo Horizonte	MG, Brazil	Brazil	30110-934
56	Trius investigator site 361	Belo Horizonte	MG, Brazil	Brazil	30140-062
57	Trius investigator site 363	Porto Alegre	RS, Brazil	Brazil	90110-270
58	Trius investigator site 364	Campinas	SP, Brazil	Brazil	13060-904
59	Trius investigator site 361	Belo Horizonte		Brazil
60	Trius investigator site 362	Belo Horizonte		Brazil
61	Trius investigator site 365	Belo Horizonte		Brazil
62	Trius investigator site 364	Campinas		Brazil
63	Trius investigator site 366	Curitiba		Brazil
64	Trius investigator site 367	Curitiba		Brazil
65	Trius investigator site 369	Jaú		Brazil
66	Trius investigator site 363	Porto Alegre		Brazil
67	Trius investigator site 370	Porto Alegre		Brazil
68	Trius investigator site 360	São Paulo		Brazil
69	Trius investigator site 206	Quedlinburg	Sachsen-Anhalt	Germany	06484
70	Trius investigator site 208	Dresden	Sachsen	Germany	01307
71	Trius investigator site 204	Luebeck	Schleswig-Holstein	Germany	23538
72	Trius investigator site 207	Berlin		Germany	10249
73	Trius investigator site 205	Hamburg		Germany	20246
74	Trius investigator site 380	Guadalajara		Mexico
75	Trius investigator site 381	Guadalajara		Mexico
76	Trius investigator site 382	Mexico, DF		Mexico
77	Trius investigator site 383	Monterrey		Mexico
78	Trius investigator 521	Otahuhu	Auckland	New Zealand
79	Trius investigator 520	Sydenham	Christchurch	New Zealand	8024
80	Trius investigator site 216	Bydgoszcz		Poland	85-094
81	Trius investigator site 211	Lodz		Poland	93-513
82	Trius investigator site 214	Lublin		Poland	20-081
83	Trius investigator site 213	Poznan		Poland	60-631
84	Trius investigator site 215	Szczecin		Poland	70-111
85	Trius investigator site 212	Warszawa		Poland	02-097
86	Trius investigator site 292	Vsevolozhsk	Leningrad Region	Russian Federation	188640
87	Trius investigator site 287	Barmaul		Russian Federation	656024
88	Trius investigator site 286	Irkutsk		Russian Federation	664079
89	Trius investigator site 293	Lipetsk		Russian Federation	389035/398005
90	Trius investigator site 295	Moscow		Russian Federation	115093
91	Trius investigator site 290	Moscow		Russian Federation	115280
92	Trius investigator site 291	Moscow		Russian Federation	115280
93	Trius investigator site 288	Moscow		Russian Federation	119435
94	Trius investigator site 297	Novosibirsk		Russian Federation	630008
95	Trius investigator site 285	Novosibirsk		Russian Federation	630051
96	Trius investigator site 294	saint-Petersburg		Russian Federation	194291
97	Trius investigator site 289	Saint-Petersburg		Russian Federation	198099
98	Trius investigator site 296	Saint-Petersburg		Russian Federation
99	Trius investigator site 289	St-Petersburg		Russian Federation	198099
100	Trius investigator site 298	Tomsk		Russian Federation	634063
101	Trius investigator 444	Worscester	Cape	South Africa	6850
102	Trius investigator 443	Port Elizabeth	Eastern Cape	South Africa	6020
103	Trius investigator site 442	Bloemfontein	Free States	South Africa	9317
104	Trius investigator site 441	Blowmfontein	Free States	South Africa	9301
105	Trius investigator 451	Centurion	Gauteng	South Africa	0157
106	Trius investigator site 440	Gezina Pretoria	Gauteng	South Africa	0084
107	Trius investigator 450	Pretoria	Gauteng	South Africa	0083
108	Trius investigator 449	Pretoria	Gauteng	South Africa	0084
109	Trius investigator 448	Dundee	Kwa Zulu Natal	South Africa	3000
110	Trius investigator 446	Middelburg	Mpumalanga	South Africa	1051
111	Trius investigator 447	Breyten	Mpunalanga	South Africa	2330
112	Trius investigator site 445	Benoni		South Africa	1501
113	Trius investigator site 273	Mataro	Barcelona	Spain	08304
114	Trius investigator site 272	Alcorcon	Madrid	Spain	28922
115	Trius investigator site 275	Majadahonda	Madrid	Spain	28222
116	Trius investigator site 277	Baracaldo	Vizcaya	Spain	48903
117	Trius investigator site 276	Madrid		Spain	28046
118	Trius investigator site 274	Santander		Spain	39008

Sponsors and Collaborators

• Trius Therapeutics LLC

Investigators

• Study Director: Philippe G Prokocimer, MD, Trius Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Trius Therapeutics LLC
• ClinicalTrials.gov Identifier: NCT01421511
• Other Study ID Numbers: 1986-010; TR701-113
• First Posted: Aug 22, 2011
• Last Update Posted: Aug 29, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Trius Therapeutics LLC: ABSSSI; Tedizolid Phosphate; TR-701; Acute Bacterial Skin and Skin Structure Infections
• Additional relevant MeSH terms: Infections; Bacterial Infections; Linezolid

Study Results

Participant Flow

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Period Title: Overall Study
STARTED	332	334
COMPLETED	313	306
NOT COMPLETED	19	28

Baseline Characteristics

Arm/Group Title	Tedizolid Phosphate	Linezolid	Total
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.	Total of all reporting groups
Overall Participants	332	334	666
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.6 (15.79)	45.6 (15.57)	45.6 (15.67)
Sex: Female, Male (Count of Participants)
Female	107 32.2%	120 35.9%	227 34.1%
Male	225 67.8%	214 64.1%	439 65.9%

Outcome Measures

1. Primary Outcome

Title	The Early Clinical Response Rate
Description	Responder: No increase in lesion surface area from baseline.
Time Frame	48-72 hours

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Number [participants]	283 85.2%	276 82.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI was calculated for the observed differences in the early clinical response rates at 48 to 72 Hours after the first infusion of study drug using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -3.0 to 8.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid responder rate minus the linezolid responder rate.

2. Secondary Outcome

Title	Clinical Response at the End of Therapy Visit
Description	Responder: No increase in lesion surface area from baseline.
Time Frame	Day 11

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Number [participants]	289 87%	294 88%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI was calculated for the observed differences in the programmatic clinical response at the EOT visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -6.1 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.

3. Secondary Outcome

Title	Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set
Description	Responder: No increase in lesion surface area from baseline.
Time Frame	End of Therapy Day 11

Outcome Measure Data

Analysis Population Description

All randomized participants receiving minimal study therapy, completed EOT assessment, no concomitant systemic antibiotic therapy and no confounding events or factors.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	304	299
Number [participants]	272 81.9%	280 83.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the EOT Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -8.8 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.

4. Secondary Outcome

Title	Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit
Description	Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, and no further antibiotic therapy required for treatment of primary ABSSSI lesion.
Time Frame	Post-Treatment Evaluation (7-14 days after the End of Therapy)

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Number [participants]	292 88%	293 87.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI was calculated for the observed differences in the clinical success rate based on the Investigator's assessment of clinical response at the PTE Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -4.8 to 5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical success rate minus the linezolid clinical success rate.

5. Secondary Outcome

Title	Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set.
Description	Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, no new signs, symptoms or complications attributable to the ABSSSI and no further antibiotic therapy required for treatment of primary ABSSSI lesion.
Time Frame	Post-Treatment Evaluation (7-14 days after the End of Therapy)

Outcome Measure Data

Analysis Population Description

All randomized participants receiving minimal study therapy, completed EOT and PTE Investigator's assessments, no concomitant systemic antibiotic therapy through PTE, and no confounding events or factors.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	290	280
Number [participants]	268 80.7%	269 80.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% CI was calculated for the observed differences in the clinical success rate based on the Investigator's assessment of clinical response at the PTE Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -7.7 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical success rate minus the linezolid clinical success rate.

6. Secondary Outcome

Title	Investigator's Assessment of Clinical Response at the 48-72 Hour Visit
Description	Clinical improvement defined as improvement in overall clinical status.
Time Frame	48-72 Hours

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Number [participants]	304 91.6%	302 90.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments	A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the 48-72 Hour Visit using the method of Miettinen and Nurminen without stratification.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -3.3 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.

7. Secondary Outcome

Title	Investigator's Assessment of Clinical Response at the Day-7 Visit
Description	Clinical improvement defined as improvement in overall clinical status.
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Number [participants]	309 93.1%	308 92.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tedizolid Phosphate, Linezolid
	Comments	A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the Day 7 Visit using the method of Miettinen and Nurminen without stratification.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -3.2 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.

8. Secondary Outcome

Title	Change From Baseline in Patient-reported Pain, by Study Visit
Description	0=no pain, 10=worst pain Only 1 visit per participant for Day 4-6, only 1 visit for Day 7-9, and only 1 visit for Day 10-13.
Time Frame	Multiple

Outcome Measure Data

Analysis Population Description

The Intent to Treat analysis set includes data from all randomized participants.

Arm/Group Title	Tedizolid Phosphate	Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	IV to oral linezolid 600 mg twice daily for 10 days.
Measure Participants	332	334
Day 2	-1.7 (2.05)	-2.1 (2.29)
Day 4-6	-3.1 (2.67)	-3.3 (2.56)
Day 7-9	-4.9 (2.89)	-4.9 (2.96)
Day 10-13	-5.4 (2.80)	-5.6 (2.84)

Adverse Events

Time Frame	Collected from signing of the ICF through the late follow-up visit (up to 38 days).
Adverse Event Reporting Description	Numbers for at risk include all treated participants.
Arm/Group Title	Tedizolid Phosphate		Linezolid
Arm/Group Description	IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.		IV to oral linezolid 600 mg twice daily for 10 days.
All Cause Mortality
	Tedizolid Phosphate		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tedizolid Phosphate		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/331 (2.1%)		9/327 (2.8%)
Cardiac disorders
Acute coronary syndrome	0/331 (0%)		1/327 (0.3%)
Acute myocardial infarction	0/331 (0%)		1/327 (0.3%)
Myocardial infarction	1/331 (0.3%)		0/327 (0%)
Immune system disorders
Anaphylactic reaction	0/331 (0%)		1/327 (0.3%)
Infections and infestations
Cellutitis	0/331 (0%)		2/327 (0.6%)
Escherichia urinary tract infection	1/331 (0.3%)		0/327 (0%)
Meningitis tuberculous	0/331 (0%)		1/327 (0.3%)
Pneumonia	1/331 (0.3%)		0/327 (0%)
Septic shock	1/331 (0.3%)		0/327 (0%)
Staphyloccal bacteraemia	1/331 (0.3%)		0/327 (0%)
Urinary tract infection bacterial	0/331 (0%)		1/327 (0.3%)
Investigations
Blood glucose increased	0/331 (0%)		1/327 (0.3%)
Metabolism and nutrition disorders
Diabetes mellitus	1/331 (0.3%)		0/327 (0%)
Renal and urinary disorders
Nephrolithiasis	1/331 (0.3%)		0/327 (0%)
Vascular disorders
Hypertension	1/331 (0.3%)		0/327 (0%)
Thrombophlebitis superficial	0/331 (0%)		1/327 (0.3%)
Other (Not Including Serious) Adverse Events
	Tedizolid Phosphate		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/331 (25.4%)		90/327 (27.5%)
Gastrointestinal disorders
Diarrhoea	11/331 (3.3%)		17/327 (5.2%)
Nausea	26/331 (7.9%)		36/327 (11%)
Vomiting	10/331 (3%)		17/327 (5.2%)
General disorders
Fatigue	8/331 (2.4%)		7/327 (2.1%)
Infections and infestations
Abscess	14/331 (4.2%)		10/327 (3.1%)
Cellulitis	9/331 (2.7%)		6/327 (1.8%)
Vulvovaginal mycotic infection	2/331 (0.6%)		7/327 (2.1%)
Nervous system disorders
Dizziness	4/331 (1.2%)		7/327 (2.1%)
Headache	20/331 (6%)		22/327 (6.7%)

Limitations/Caveats

Analyses for this study were conducted using 2 statistical plans, 1 for the US FDA and 1 for the EMA, to address differing guidance on the development of antibacterials. These differences are reflected in the EudraCT and clinicaltrials.gov records.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor intends to pursue publication of the results of the study in cooperation with a lead Investigator, subject to the terms and conditions of the clinical study agreement between the Sponsor and Investigators. Sponsor approval in writing is required for publication of any data subsets. Final authorship will be determined in accordance with the International Committee of Medical Journal Editors definition of authorship.