Trial Outcomes & Findings for Retapamulin Versus Linezolid in the Treatment of SITL and Impetigo Due to MRSA (NCT NCT00852540)

Last Updated: 2017-03-27

Results Overview

Follow-up is defined as 7-9 days post-therapy: Day 12-14 for retapamulin; Day 17-19 for linezolid. Clinical success at follow-up was defined as the resolution of clinically meaningful signs and symptoms of infection recorded at baseline, including a pus/exudate skin infection rating scale (SIRS) score of "0." The SIRS is used by the investigator to evaluate infected lesions. Scores on the SIRS range from 0 (absent) to 6 (severe).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

410 participants

Primary outcome timeframe

7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Results posted on

2017-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Overall Study STARTED	270	140
Overall Study COMPLETED	234	122
Overall Study NOT COMPLETED	36	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Overall Study Adverse Event	10	3
Overall Study Lack of Efficacy	15	3
Overall Study Protocol Violation	1	2
Overall Study Lost to Follow-up	2	3
Overall Study Investigator Discretion	2	3
Overall Study Withdrawal by Subject	3	1
Overall Study Did Not Receive Study Drug	3	3

Baseline Characteristics

Retapamulin Versus Linezolid in the Treatment of SITL and Impetigo Due to MRSA

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=267 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=137 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.	Total n=404 Participants Total of all reporting groups
Age, Continuous	34.6 Years STANDARD_DEVIATION 21.37 • n=5 Participants	33.8 Years STANDARD_DEVIATION 22.38 • n=7 Participants	34.3 Years STANDARD_DEVIATION 21.69 • n=5 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	49 Participants n=7 Participants	157 Participants n=5 Participants
Sex: Female, Male Male	159 Participants n=5 Participants	88 Participants n=7 Participants	247 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	16 participants n=5 Participants	10 participants n=7 Participants	26 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 participants n=5 Participants	0 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized East Asian Heritage	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Japanese Heritage	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized South East Asian Heritage	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Arabic/North African Heritage	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian/European	222 participants n=5 Participants	118 participants n=7 Participants	340 participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	10 participants n=5 Participants	1 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Population: Intent-to-Treat MRSA (ITTMRSA) Population: all randomized participants who took at least one dose of study medication and who had an MRSA isolated at baseline.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=72 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=38 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen	41 participants	32 participants

SECONDARY outcome

Timeframe: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Population: Intent-to-Treat MRSA (ITTMRSA) Population: all randomized participants who took at least one dose of study medication and who had an MRSA isolated at baseline.

MR was defined as microbiological success if, (1) for participants (par.) whose clinical outcome at end of therapy (EOT) was "clinical success (CS)/improvement," the BP was eradicated/presumed to be eradicated at EOT, or the BP was present at EOT and absent at FU, or the BP was eradicated/presumed to be eradicated at EOT, or the BP was present at EOT and par. was a "CS" such that no culture was obtained due to lack of culturable material secondary to adequate clinical response; or (2) a pathogen not previously identified at baseline was isolated at FU in a par. identified at FU as a "CS."

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=72 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=38 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP)	41 participants	32 participants

SECONDARY outcome

Timeframe: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Population: Intent-to-Treat Clinical (ITTC) Population: all randomized participants (par.) who took at least one dose of study medication. One par. was randomized to retapamulin but received linezolid. This par. is summarized in the linezolid group for all baseline and safety tables, but is summarized in the retapamulin group for all efficacy tables.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=268 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=136 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants With Clinical Response at Follow-up	161 participants	112 participants

SECONDARY outcome

Timeframe: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Population: Intent-to-Treat Bacteriology (ITTB) Population: all randomized participants who took at least one dose of study medication and who had a pathogen isolated at baseline.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=177 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=78 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP)	100 participants	65 participants

SECONDARY outcome

Timeframe: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid

Population: ITTMRSA Population

Clinical improvement is defined as improvement of signs/symptoms of infection recorded at baseline (BL) to such an extent that no further antimicrobial therapy is necessary. Clinical failure (CF) is defined as insufficient improvement/deterioration of signs/symptoms of the infection recorded at BL, such that additional antibiotic therapy is required. Unable to determine (UTD) is defined as refusal to consent to a clinical examination, lost to follow-up. Participants who are "CF"/"Unable to Determine" at end of therapy are considered such at follow-up as well.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=72 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=38 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen Clinical success	20 participants	28 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen Clinical improvement	42 participants	9 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen Clinical failure	8 participants	1 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen Unable to determine	2 participants	0 participants

SECONDARY outcome

Timeframe: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid

Population: ITTMRSA Population

Eradication is the elimination of BL pathogens. Presumed eradication and presumed improvement are clinical outcomes of success or improvement, respectively, such that no culture was obtained due to lack of culturable material, secondary to adequate clinical response, and is documented in the electronic Case Report Form. Persistence is defined as BL pathogens still being present. Presumed persistence is defined as a participant that is a clinical failure with no obtained culture. "Unable to determine" was used if no determination of BL pathogen microbiological response could be made.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=72 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=38 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Persistence	4 participants	1 participants
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Eradication	1 participants	0 participants
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Presumed eradication	20 participants	28 participants
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Presumed improvement	42 participants	9 participants
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Presumed persistence	4 participants	0 participants
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen Unable to determine	1 participants	0 participants

SECONDARY outcome

Timeframe: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid

Population: ITTC Population. One par. was randomized to retapamulin but received linezolid. This par. is summarized in the linezolid group for all baseline and safety tables, but is summarized in the retapamulin group for all efficacy tables.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=268 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=136 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Clinical success	92 participants	96 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Clinical improvement	155 participants	34 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Clinical failure	16 participants	4 participants
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Unable to determine	5 participants	2 participants

SECONDARY outcome

Timeframe: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid

Population: ITTB Population

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=177 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=78 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Eradication	2 pathogens	1 pathogens
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Presumed eradication	63 pathogens	70 pathogens
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Presumed improvement	120 pathogens	21 pathogens
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Persistence	7 pathogens	1 pathogens
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Presumed persistence	9 pathogens	1 pathogens
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy Unable to determine	1 pathogens	0 pathogens

SECONDARY outcome

Timeframe: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid

Population: ITTB Population

Therapeutic response is defined as the combined clinical and microbiological response. Therapeutic response iss a measure of the overall efficacy response, and a therapeutic success refers to participants who had been deemed both a "clinical success" and a "microbiological success." All other combinations (other than "clinical success" + "microbiological success") were deemed failures for therapeutic response.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=177 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=78 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Number of Participants With Therapeutic Response at Follow-up	100 participants	65 participants

SECONDARY outcome

Timeframe: Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19)

Population: ITTC Population. Only participants with non-missing Skin Infection Rating Scale scores were included in this analysis. One par. was randomized to retapamulin but received linezolid. This par. is summarized in the linezolid group for all baseline and safety tables, but is summarized in the retapamulin group for all efficacy tables.

The investigator evaluated skin infections by grading the infected lesion for exudate (a fluid that leaks out of blood vessels into surrounding tissue)/pus, crusting, erythema (redness of the skin)/ inflammation (E/I), tissue warmth, tissue edema (swelling), itching, and pain, according to the Skin Infection Rating Scale. All parameters were graded on a scale of 0 (absent) to 6 (severe). The total score is calculated by summing the individual scores from the 7 parameters; the total score ranges from 0 to 42.

Outcome measures

SECONDARY outcome

Timeframe: Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19)

Population: ITTC Population. Only participants with non-missing data were included in this analysis. One par. was randomized to retapamulin but received linezolid. This par. is summarized in the linezolid group for all baseline and safety tables, but is summarized in the retapamulin group for all efficacy tables.

Lesion sized was measured in centimeters squared at Visits 1, 2, 3, 4, and 5.

Outcome measures

Outcome measures
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=268 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=136 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Mean Wound Size at Visits 1, 2, 3, 4, and 5 Visit 1, n=268, 136	7.942 centimeters squared (cm^2) Standard Deviation 13.3124	5.620 centimeters squared (cm^2) Standard Deviation 9.6215
Mean Wound Size at Visits 1, 2, 3, 4, and 5 Visit 2, n=265, 135	4.963 centimeters squared (cm^2) Standard Deviation 8.5492	4.115 centimeters squared (cm^2) Standard Deviation 9.4305
Mean Wound Size at Visits 1, 2, 3, 4, and 5 Visit 3, n=255, 130	3.270 centimeters squared (cm^2) Standard Deviation 10.8663	1.776 centimeters squared (cm^2) Standard Deviation 6.7537
Mean Wound Size at Visits 1, 2, 3, 4, and 5 Visit 4, n=237, 125	1.556 centimeters squared (cm^2) Standard Deviation 5.2201	0.812 centimeters squared (cm^2) Standard Deviation 3.4217
Mean Wound Size at Visits 1, 2, 3, 4, and 5 Visit 5, n=237, 122	0.741 centimeters squared (cm^2) Standard Deviation 3.5977	0.588 centimeters squared (cm^2) Standard Deviation 3.3623

Adverse Events

Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Linezolid Plus Placebo Ointment

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=267 participants at risk Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=137 participants at risk Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Infections and infestations Cellulitis	0.75% 2/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	0.73% 1/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.
Infections and infestations Staphylococcal infection	0.37% 1/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	0.00% 0/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	0.73% 1/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	0.73% 1/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	0.73% 1/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.

Other adverse events

Other adverse events
Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=267 participants at risk Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=137 participants at risk Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Gastrointestinal disorders Diarrhea	3.0% 8/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	11.7% 16/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Nausea	2.2% 6/267 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.	7.3% 10/137 Serious adverse events and non-serious adverse events were collected in the Intent-to-Treat Clinical (ITTC) Popluation, comprised of all randomized participants who took at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo n=268 Participants Retapamulin ointment was administered topically twice daily (BID) for 5 days. The ointment formulation was to be applied to the infected lesion(s) at a dose of approximately 10 milligrams (mg) per centimeter squared (cm\^2). Placebo was to be dosed, depending on participant age, either BID or three times a day (TID) for 10 days. Placebo oral suspension and oral tablet were formulated to appear identical to the linezolid formulations. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg placebo tablets, pediatric participants 5 to 11 years of age were dosed with oral suspension at 0.5 milliliters (ml)/kilogram (kg) BID, and pediatric participants less than 5 years of age were dosed with oral suspension at 0.5 ml/kg TID.	Linezolid Plus Placebo Ointment n=136 Participants Linezolid was to be dosed, depending on participant age, either BID or TID for 10 days. Adolescent and adult participants (\>=12 years of age) were dosed BID with 600 mg tablets for 10 days. Pediatric participants who were 5-11 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg BID for 10 days. Pediatric participants who were \<5 years of age were dosed with a 100 mg/5 ml oral suspension at a dose of 10 mg/kg TID for 10 days. Placebo ointment was administered topically BID for 5 days.
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pus/exudate, Visit 4, n=237, 125	0.2 scores on a scale Standard Deviation 0.59	0.1 scores on a scale Standard Deviation 0.34
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Crusting, Visit 1, n=268, 136	2.2 scores on a scale Standard Deviation 1.48	2.1 scores on a scale Standard Deviation 1.49
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Crusting, Visit 2, n=265, 135	1.3 scores on a scale Standard Deviation 1.21	1.2 scores on a scale Standard Deviation 1.15
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue warmth, Visit 4, n=237, 125	0.1 scores on a scale Standard Deviation 0.41	0.1 scores on a scale Standard Deviation 0.34
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue warmth, Visit 5, n=238, 122	0.1 scores on a scale Standard Deviation 0.38	0.0 scores on a scale Standard Deviation 0.20
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Total score, Visit 2, n=265, 135	10.7 scores on a scale Standard Deviation 6.78	9.7 scores on a scale Standard Deviation 6.32
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Total score, Visit 3, n=255, 130	5.2 scores on a scale Standard Deviation 5.83	4.1 scores on a scale Standard Deviation 4.16
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Total score, Visit 4, n=237, 125	3.6 scores on a scale Standard Deviation 6.13	2.5 scores on a scale Standard Deviation 4.13
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Total score, Visit 5, n=238, 122	2.5 scores on a scale Standard Deviation 6.14	1.6 scores on a scale Standard Deviation 3.92
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pus/exudate, Visit 2, n=265, 135	1.7 scores on a scale Standard Deviation 1.37	1.4 scores on a scale Standard Deviation 1.25
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pus/exudate, Visit 3, n=255, 130	0.6 scores on a scale Standard Deviation 1.05	0.4 scores on a scale Standard Deviation 0.74
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pus/exudate, Visit 5, n=238, 122	0.1 scores on a scale Standard Deviation 0.39	0.0 scores on a scale Standard Deviation 0.29
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Crusting, Visit 3, n=255, 130	0.9 scores on a scale Standard Deviation 1.08	0.8 scores on a scale Standard Deviation 0.91
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Crusting, Visit 4, n=237, 125	0.6 scores on a scale Standard Deviation 0.95	0.5 scores on a scale Standard Deviation 0.83
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Crusting, Visit 5, n=238, 122	0.3 scores on a scale Standard Deviation 0.59	0.3 scores on a scale Standard Deviation 0.73
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 E/I, Visit 1, n=268, 136	3.4 scores on a scale Standard Deviation 1.09	3.4 scores on a scale Standard Deviation 1.08
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 E/I, Visit 2, n=265, 135	2.2 scores on a scale Standard Deviation 1.19	2.2 scores on a scale Standard Deviation 1.26
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 E/I, Visit 3, n=255, 130	1.1 scores on a scale Standard Deviation 1.15	1.0 scores on a scale Standard Deviation 0.93
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 E/I, Visit 4, n=237, 125	0.5 scores on a scale Standard Deviation 0.69	0.5 scores on a scale Standard Deviation 0.73
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 E/I, Visit 5, n=238, 122	0.2 scores on a scale Standard Deviation 0.54	0.2 scores on a scale Standard Deviation 0.54
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue warmth, Visit 1, n=268, 136	2.8 scores on a scale Standard Deviation 1.33	2.6 scores on a scale Standard Deviation 1.29
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue warmth, Visit 2, n=265, 135	1.4 scores on a scale Standard Deviation 1.22	1.3 scores on a scale Standard Deviation 1.22
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue warmth, Visit 3, n=255, 130	0.6 scores on a scale Standard Deviation 0.97	0.4 scores on a scale Standard Deviation 0.69
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue edema, Visit 1, n=268, 136	2.8 scores on a scale Standard Deviation 1.24	2.7 scores on a scale Standard Deviation 1.30
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue edema, Visit 2, n=265, 135	1.6 scores on a scale Standard Deviation 1.23	1.5 scores on a scale Standard Deviation 1.19
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue edema, Visit 3, n=255, 130	0.7 scores on a scale Standard Deviation 1.02	0.7 scores on a scale Standard Deviation 0.86
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue edema, Visit 4, n=237, 125	0.3 scores on a scale Standard Deviation 0.60	0.2 scores on a scale Standard Deviation 0.55
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Tissue edema, Visit 5, n=238, 122	0.1 scores on a scale Standard Deviation 0.35	0.1 scores on a scale Standard Deviation 0.36
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Itching, Visit 1, n=268, 136	1.6 scores on a scale Standard Deviation 1.51	1.8 scores on a scale Standard Deviation 1.51
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Itching, Visit 2, n=265, 135	1.0 scores on a scale Standard Deviation 1.27	0.9 scores on a scale Standard Deviation 1.11
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Itching, Visit 3, n=255, 130	0.7 scores on a scale Standard Deviation 1.24	0.6 scores on a scale Standard Deviation 1.08
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Itching, Visit 4, n=237, 125	0.3 scores on a scale Standard Deviation 0.79	0.4 scores on a scale Standard Deviation 0.76
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Itching, Visit 5, n=238, 122	0.1 scores on a scale Standard Deviation 0.42	0.2 scores on a scale Standard Deviation 0.66
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pain, Visit 1, n=268, 136	3.2 scores on a scale Standard Deviation 1.57	3.0 scores on a scale Standard Deviation 1.65
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pain, Visit 2, n=265, 135	1.5 scores on a scale Standard Deviation 1.56	1.2 scores on a scale Standard Deviation 1.39
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pain, Visit 3, n=255, 130	0.6 scores on a scale Standard Deviation 1.14	0.4 scores on a scale Standard Deviation 0.96
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pain, Visit 4, n=237, 125	0.2 scores on a scale Standard Deviation 0.60	0.1 scores on a scale Standard Deviation 0.56
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pain, Visit 5, n=238, 122	0.1 scores on a scale Standard Deviation 0.39	0.1 scores on a scale Standard Deviation 0.45
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Total score, Visit 1, n=268, 136	19.5 scores on a scale Standard Deviation 5.69	19.2 scores on a scale Standard Deviation 5.56
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 Pus/exudate, Visit 1, n=268, 136	3.6 scores on a scale Standard Deviation 0.82	3.6 scores on a scale Standard Deviation 0.8