Trial Outcomes & Findings for TR-701 FA vs. Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections. (NCT NCT01170221)

NCT ID: NCT01170221

Last Updated: 2018-08-29

Results Overview

Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

667 participants

Primary outcome timeframe

48-72 hours

Results posted on

2018-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Tedizolid Phosphate Oral Tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid Oral linezolid 600 mg twice daily for 10 days
Overall Study STARTED	332	335
Overall Study COMPLETED	299	307
Overall Study NOT COMPLETED	33	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Tedizolid Phosphate Oral Tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid Oral linezolid 600 mg twice daily for 10 days
Overall Study Lost to Follow-up	22	21
Overall Study Withdrawal by Subject	9	7
Overall Study Subject completed only screening and LFU	1	0
Overall Study Randomized but not treated	1	0

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 Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days	Total n=667 Participants Total of all reporting groups
Age, Continuous	43.6 Years STANDARD_DEVIATION 14.96 • n=5 Participants	43.1 Years STANDARD_DEVIATION 15.06 • n=7 Participants	43.3 Years STANDARD_DEVIATION 15.0 • n=5 Participants
Sex: Female, Male Female	128 Participants n=5 Participants	137 Participants n=7 Participants	265 Participants n=5 Participants
Sex: Female, Male Male	204 Participants n=5 Participants	198 Participants n=7 Participants	402 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48-72 hours

Population: The ITT analysis set includes data from all randomized participants.

Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Early Clinical Response Rate	264 Responders Interval -6.1 to 6.2	266 Responders Interval -6.1 to 6.2

SECONDARY outcome

Timeframe: Day 11

Population: The ITT analysis set includes data from all randomized participants.

Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit.	230 participants	241 participants

SECONDARY outcome

Timeframe: EOT Day 11

Population: All randomized patients receiving minimal study therapy, completed 48-72 Hour and EOT assessments, no concomitant systemic antibiotic therapy through EOT, and had no confounding events or factors

Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=273 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=286 Participants Oral linezolid 600 mg twice daily for 10 days
Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit in the Clinically Evaluable-End of Therapy Analysis Sets	219 participants	232 participants

SECONDARY outcome

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

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

Clinical success defined as resolution/near resolution of most disease-specific signs and symptoms, absence/near resolution of systemic signs of infection, if present at baseline, no new signs, symptoms, or complications attributable to the ABSSSIs so no further antibiotic therapy was required for the treatment of the primary lesion.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit	284 participants	288 participants

SECONDARY outcome

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

Population: All randomized patients who received the minimal study therapy, completed EOT and PTE assessments, no concomitant systemic antibiotic therapy through PTE, and had no confounding events or factors.

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

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=279 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=280 Participants Oral linezolid 600 mg twice daily for 10 days
To Compare the Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit in the Clinically Evaluable-Post Treatment Evaluation Analysis Set	264 participants	267 participants

SECONDARY outcome

Timeframe: 48-72 Hour Visit

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

Clinical improvement was defined as improvement in overall clinical status.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Investigator's Assessment of Clinical Response at the 48-72 Hour Visit	299 participants	290 participants

SECONDARY outcome

Timeframe: Day 7

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

Clinical improvement was defined as improvement in overall clinical status.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate n=332 Participants Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Investigator's Assessment of Clinical Response at the Day 7 Visit	302 participants	299 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 Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 Participants Oral linezolid 600 mg twice daily for 10 days
Change From Baseline in Patient-reported Pain, by Study Visit Day 2	-1.3 units on a scale Standard Deviation 2.05	-1.5 units on a scale Standard Deviation 1.99
Change From Baseline in Patient-reported Pain, by Study Visit Day 4-6	-3.4 units on a scale Standard Deviation 2.44	-3.1 units on a scale Standard Deviation 2.41
Change From Baseline in Patient-reported Pain, by Study Visit Day 7-9	-4.5 units on a scale Standard Deviation 2.71	-4.6 units on a scale Standard Deviation 2.67
Change From Baseline in Patient-reported Pain, by Study Visit Day 10-13	-5.3 units on a scale Standard Deviation 2.65	-5.5 units on a scale Standard Deviation 2.58

Adverse Events

Tedizolid Phosphate

Serious events: 5 serious events

Other events: 84 other events

Deaths: 0 deaths

Linezolid

Serious events: 4 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tedizolid Phosphate n=331 participants at risk Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 participants at risk Oral linezolid 600 mg twice daily for 10 days
Gastrointestinal disorders Nausea	8.5% 28/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	13.4% 45/335 • 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	6.3% 21/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	5.1% 17/335 • 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 Diarrhea	4.5% 15/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	5.4% 18/335 • 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.	2.4% 8/335 • 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 limb	3.6% 12/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	3.0% 10/335 • 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	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.	6.0% 20/335 • 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	2.4% 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.	2.4% 8/335 • 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	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% 7/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Skin and subcutaneous tissue disorders Pruritus	0.91% 3/331 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.	2.4% 8/335 • 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 Dyspepsia	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% 7/335 • 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 results in cooperation with a lead Investigator, subject to the terms and conditions of the clinical study agreement between the Sponsor and Investigators. Sponsor approval 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 Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo	Linezolid n=335 participants at risk Oral linezolid 600 mg twice daily for 10 days
Cardiac disorders Cardiac arrest	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% 0/335 • 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 Gastrointestinal haemorrhage	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% 0/335 • 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	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% 0/335 • 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	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% 0/335 • 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 Endophthalmitis	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% 0/335 • 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% 0/335 • 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% 0/335 • 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 Weight decreased	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% 0/335 • 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 Dehydration	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% 0/335 • 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 Diabetic ketoacidosis	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.	0.30% 1/335 • 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 VIIth nerve paralysis	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% 0/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	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.	0.30% 1/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Psychiatric disorders Alcoholic psychosis	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.	0.30% 1/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Psychiatric disorders Major depression	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.	0.30% 1/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.
Psychiatric disorders Suicidal ideation	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.	0.30% 1/335 • Collected from signing of the ICF through the late follow-up visit (up to 38 days). Numbers for at risk include all treated participants.