Trial Outcomes & Findings for Omadacycline Versus Linezolid for the Treatment of ABSSSI (EudraCT #2013-003644-23) (NCT NCT02378480)

Last Updated: 2019-03-21

Results Overview

Early clinical response is defined as clinical success, which is categorized as survival with at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to Screening measurements, without receiving any rescue antibacterial therapy. An indeterminate classification is used for a response that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

655 participants

Primary outcome timeframe

Screening; 48 to 72 hours after the first dose of test article

Results posted on

2019-03-21

Participant Flow

The study was designed to enroll adult participants with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) that was known or suspected to be due to a Gram-positive pathogen(s). Randomization was stratified across treatment groups by type of infection (wound infection, cellulitis/erysipelas, and major abscess) and geographic region.

Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group, and received their first dose of test article within 4 hours after randomization. All participants were expected to present with ABSSSI severe enough to require a minimum of at least 3 days of intravenous treatment.

Participant milestones

Participant milestones
Measure	Omadacycline Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Overall Study STARTED	329	326
Overall Study COMPLETED	301	294
Overall Study NOT COMPLETED	28	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Omadacycline Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Overall Study Physician Decision	1	1
Overall Study Death	1	2
Overall Study Randomized, but Not Treated	6	4
Overall Study Adverse Event	0	1
Overall Study Missed EOT/PTE Visit	1	2
Overall Study Withdrawal by Subject	9	4
Overall Study Lost to Follow-up	10	18

Baseline Characteristics

Omadacycline Versus Linezolid for the Treatment of ABSSSI (EudraCT #2013-003644-23)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omadacycline n=323 Participants Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=322 Participants Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.	Total n=645 Participants Total of all reporting groups
Age, Customized 18-45 years	146 Participants n=5 Participants	154 Participants n=7 Participants	300 Participants n=5 Participants
Age, Customized >45-65 years	141 Participants n=5 Participants	136 Participants n=7 Participants	277 Participants n=5 Participants
Age, Customized >65 years	36 Participants n=5 Participants	32 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Female	120 Participants n=5 Participants	109 Participants n=7 Participants	229 Participants n=5 Participants
Sex: Female, Male Male	203 Participants n=5 Participants	213 Participants n=7 Participants	416 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	8 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	294 Participants n=5 Participants	300 Participants n=7 Participants	594 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening; 48 to 72 hours after the first dose of test article

Population: Modified Intent-to-Treat (mITT) Population: all randomized participants without a baseline sole Gram-negative ABSSSI pathogen

Outcome measures

Outcome measures
Measure	Omadacycline n=316 Participants Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=311 Participants Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Number of Participants With Early Clinical Response Clinical success	268 Participants	266 Participants
Number of Participants With Early Clinical Response Clinical failure	23 Participants	19 Participants
Number of Participants With Early Clinical Response Indeterminate	25 Participants	26 Participants

SECONDARY outcome

Timeframe: Screening; 7 to 14 days after the last day of therapy

Population: mITT Population

At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the infection was sufficiently resolved such that further antibacterial therapy was not needed. These participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the End-of-Treatment (EOT) Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation. Indeterminate: clinical response to test article could not be adequately inferred.

Outcome measures

Outcome measures
Measure	Omadacycline n=316 Participants Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=311 Participants Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit Clinical failure	20 Participants	27 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit Indeterminate	24 Participants	24 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit Clinical success	272 Participants	260 Participants

SECONDARY outcome

Timeframe: Screening; 7 to 14 days after the last day of therapy

Population: CE-PTE Population: all participants in the mITT Population meeting additional pre-defined criteria

At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the infection was sufficiently resolved such that further antibacterial therapy was not needed. These participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the EOT Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation.

Outcome measures

Outcome measures
Measure	Omadacycline n=269 Participants Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=260 Participants Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population Clinical failure	10 Participants	17 Participants
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population Clinical success	259 Participants	243 Participants

SECONDARY outcome

Timeframe: 0 to 37 days

Population: Safety Population: all randomized participants who received test article

An AE is defined as any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given a test article or in a clinical study. The event does not need to be causally related to the test article or clinical study. A serious adverse event (SAE) is defined as an event that resulted in death, was life-threatening, required hospitalization or prolongation of an existing hospitalization, resulted in a persistent or significant disability or incapacity, resulted in cancer, or resulted in a congenital anomaly or birth defect. A treatment-emergent AE (TEAE) is defined as any AE that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article. Vital sign measurements, electrocardiogram findings, and laboratory values classified as adverse events were included in the analysis. Data are presented as the number of participants with at least 1 of the event.

Outcome measures

Outcome measures
Measure	Omadacycline n=323 Participants Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=322 Participants Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Number of Participants With the Indicated Type of Adverse Event (AE) Serious TEAE leading to death	1 Participants	2 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) TEAE leading to premature drug discontinuation	6 Participants	7 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) TEAE	156 Participants	147 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Drug-releated AE	58 Participants	59 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) AE	158 Participants	157 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Severe TEAE	6 Participants	10 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Serious TEAE	12 Participants	8 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Drug-related serious TEAE	0 Participants	0 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) TEAE leading to premature discontinuation of study	6 Participants	7 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) TEAE leading to dose interruption	2 Participants	0 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Serious TEAEs leading to drug discontinuation	3 Participants	3 Participants

Adverse Events

Omadacycline

Serious events: 12 serious events

Other events: 104 other events

Deaths: 1 deaths

Linezolid

Serious events: 8 serious events

Other events: 101 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Omadacycline n=323 participants at risk Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=322 participants at risk Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Gastrointestinal disorders Nausea	12.4% 40/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	9.9% 32/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Gastrointestinal disorders Vomiting	5.3% 17/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	5.0% 16/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Gastrointestinal disorders Diarrhea	2.2% 7/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	3.1% 10/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
General disorders Infusion site extravasation	8.7% 28/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	5.9% 19/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Subcutaneous abscess	5.0% 16/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	5.9% 19/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Cellulitis	4.0% 13/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	4.3% 14/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Wound infection	2.5% 8/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	1.6% 5/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Investigations Alanine aminotransferase increased	2.8% 9/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	4.3% 14/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Investigations Aspartate aminotransferase increased	2.5% 8/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	3.7% 12/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Nervous system disorders Headache	3.1% 10/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	4.0% 13/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Skin and subcutaneous tissue disorders Pruritus	2.2% 7/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.

Additional Information

Dr. Paul McGovern; Vice President, Clinical Affairs

Paratek Pharmaceuticals, Inc.

Phone: 484-751-4935

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.
Publication restrictions are in place

Restriction type: OTHER

Measure	Omadacycline n=323 participants at risk Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 12 hours (q12h) (2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg oral administration q24h after a minimum of 3 days (6 doses) of IV treatment (6 overall IV doses because of the blinding). Participants received 4 active doses plus 2 placebo doses to maintain the blind. The total treatment duration was 7 to 14 days.	Linezolid n=322 participants at risk Participants received linezolid 600 mg IV q12h with the option to switch to a 600 mg oral administration q12h after a minimum of 3 days (6 doses) of IV treatment. The total treatment duration was 7 to 14 days.
Cardiac disorders Cardiac Arrest	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Cardiac disorders Cardiac Failure	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
General disorders Non-Cardiac Chest Pain	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Cellulitis	0.62% 2/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Subcutaneous Abscess	0.62% 2/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Wound Infection	0.62% 2/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Bacteraemia	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Gastroenteritis Rotavirus	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Infections and infestations Sepsis	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Injury, poisoning and procedural complications Joint Dislocation	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Injury, poisoning and procedural complications Overdose	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Nervous system disorders Hemiparesis	0.31% 1/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.00% 0/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Psychiatric disorders Drug Abuse	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/323 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.	0.31% 1/322 • Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the start of the first infusion of test article). Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article. Safety assessments included clinical review of reported adverse events and serious adverse events (SAEs). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.