Trial Outcomes & Findings for TR-701 FA vs Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections (NCT NCT01421511)

NCT ID: NCT01421511

Last Updated: 2018-08-29

Results Overview

Responder: No increase in lesion surface area from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

666 participants

Primary outcome timeframe

48-72 hours

Results posted on

2018-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Tedizolid Phosphate IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	Linezolid IV to oral linezolid 600 mg twice daily for 10 days.
Overall Study STARTED	332	334
Overall Study COMPLETED	313	306
Overall Study NOT COMPLETED	19	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Tedizolid Phosphate IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	Linezolid IV to oral linezolid 600 mg twice daily for 10 days.
Overall Study Lost to Follow-up	11	14
Overall Study Randomized but didn't receive study drug	1	7
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	6	5
Overall Study Death	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.	Total n=666 Participants Total of all reporting groups
Age, Continuous	45.6 years STANDARD_DEVIATION 15.79 • n=5 Participants	45.6 years STANDARD_DEVIATION 15.57 • n=7 Participants	45.6 years STANDARD_DEVIATION 15.67 • n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	120 Participants n=7 Participants	227 Participants n=5 Participants
Sex: Female, Male Male	225 Participants n=5 Participants	214 Participants n=7 Participants	439 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48-72 hours

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

Responder: No increase in lesion surface area from baseline.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
The Early Clinical Response Rate	283 participants	276 participants

SECONDARY outcome

Timeframe: Day 11

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

Responder: No increase in lesion surface area from baseline.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Clinical Response at the End of Therapy Visit	289 participants	294 participants

SECONDARY outcome

Timeframe: End of Therapy Day 11

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

Responder: No increase in lesion surface area from baseline.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=304 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=299 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set	272 participants	280 participants

SECONDARY outcome

Timeframe: Post-Treatment Evaluation (7-14 days after the End of Therapy)

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

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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit	292 participants	293 participants

SECONDARY outcome

Timeframe: Post-Treatment Evaluation (7-14 days after the End of Therapy)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=290 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=280 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set.	268 participants	269 participants

SECONDARY outcome

Timeframe: 48-72 Hours

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

Clinical improvement defined as improvement in overall clinical status.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Investigator's Assessment of Clinical Response at the 48-72 Hour Visit	304 participants	302 participants

SECONDARY outcome

Timeframe: Day 7

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

Clinical improvement defined as improvement in overall clinical status.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Investigator's Assessment of Clinical Response at the Day-7 Visit	309 participants	308 participants

SECONDARY outcome

Timeframe: Multiple

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

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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.	Linezolid n=334 Participants IV to oral linezolid 600 mg twice daily for 10 days.
Change From Baseline in Patient-reported Pain, by Study Visit Day 7-9	-4.9 units on a scale Standard Deviation 2.89	-4.9 units on a scale Standard Deviation 2.96
Change From Baseline in Patient-reported Pain, by Study Visit Day 10-13	-5.4 units on a scale Standard Deviation 2.80	-5.6 units on a scale Standard Deviation 2.84
Change From Baseline in Patient-reported Pain, by Study Visit Day 2	-1.7 units on a scale Standard Deviation 2.05	-2.1 units on a scale Standard Deviation 2.29
Change From Baseline in Patient-reported Pain, by Study Visit Day 4-6	-3.1 units on a scale Standard Deviation 2.67	-3.3 units on a scale Standard Deviation 2.56

Adverse Events

Tedizolid Phosphate

Serious events: 7 serious events

Other events: 84 other events

Deaths: 0 deaths

Linezolid

Serious events: 9 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tedizolid Phosphate n=331 participants at risk IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	Linezolid n=327 participants at risk IV to oral linezolid 600 mg twice daily for 10 days.
Gastrointestinal disorders Diarrhoea	3.3% 11/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	5.2% 17/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Gastrointestinal disorders Nausea	7.9% 26/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	11.0% 36/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Gastrointestinal disorders Vomiting	3.0% 10/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	5.2% 17/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
General disorders Fatigue	2.4% 8/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	2.1% 7/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Abscess	4.2% 14/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	3.1% 10/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Cellulitis	2.7% 9/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	1.8% 6/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Vulvovaginal mycotic infection	0.60% 2/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	2.1% 7/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Nervous system disorders Dizziness	1.2% 4/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	2.1% 7/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Nervous system disorders Headache	6.0% 20/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	6.7% 22/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.

Additional Information

Philippe Prokocimer, MD

Cubist Pharmaceuticals, Inc.

Phone: 858-452-0370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tedizolid Phosphate n=331 participants at risk IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.	Linezolid n=327 participants at risk IV to oral linezolid 600 mg twice daily for 10 days.
Cardiac disorders Acute coronary syndrome	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Cardiac disorders Acute myocardial infarction	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Cardiac disorders Myocardial infarction	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Immune system disorders Anaphylactic reaction	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Cellutitis	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.61% 2/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Escherichia urinary tract infection	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Meningitis tuberculous	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Pneumonia	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Septic shock	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Staphyloccal bacteraemia	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Infections and infestations Urinary tract infection bacterial	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Investigations Blood glucose increased	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Metabolism and nutrition disorders Diabetes mellitus	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Renal and urinary disorders Nephrolithiasis	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Vascular disorders Hypertension	0.30% 1/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.00% 0/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Vascular disorders Thrombophlebitis superficial	0.00% 0/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	0.31% 1/327 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.