Skin Infections, Bacterial
Conditions
Keywords
impetigo, methicillin-resistant Staphylococcus aureus, linezolid, secondarily-infected traumatic lesion, uncomplicated skin infection, retapamulin
Brief summary
The purpose of this study is to provide further evidence of the clinical and bacteriological efficacy of retapamulin in the treatment of subjects with SITL or impetigo due to MRSA. Subjects aged 2 months and older will be treated with either topical retapamulin for 5 days or oral linezolid for 10 days. The primary endpoint is the clinical response at follow-up (7-9 days after the end of therapy) in subjects who have a MRSA infection at baseline. The primary population is the per-protocol MRSA population. It is anticipated that approximately 500 subjects may be enrolled in order to obtain approximately 105 subjects who have a baseline MRSA infection.
Detailed description
This is a prospective, randomized, double-blind, double dummy, multicenter, comparative study in subjects 2 months of age and older with SITL (including secondarily-infected lacerations, sutured wounds and abrasions) or impetigo (bullous and non-bullous) due to MRSA. A laceration or sutured wound cannot exceed 10 cm in length with surrounding erythema not extending more than 2 cm from the edge of the lesion. Abrasions cannot exceed 100 cm2 in total area, or up to a maximum of 2% total body surface area for subjects \<18 years of age, with surrounding erythema not extending more than 2 cm from the edge of the abrasion. Subjects with impetigo can have up to 10 lesions and the infected lesion(s) must not be more than 100 cm2 in area (or up to a maximum of 2% total body surface area for subjects \<18 years of age), must not require surgical intervention and must be able to be appropriately treated with a topical antibiotic. There are five study visits occurring over a 17-19 day period. At the baseline visit (Visit 1, day 1), subjects will be randomized to receive retapamulin (plus oral placebo) or linezolid (plus placebo ointment) in a 2:1 ratio. Retapamulin is applied twice daily for 5 days, and linezolid is dosed, depending on subject age, either twice or three times daily for 10 days. The on-therapy, end of therapy and follow-up visits are staggered due to the difference in duration of the treatment regimens. Subjects will be monitored and clinically evaluated at all postbaseline visits. Randomization will be center-based and stratified by age (\<5 years, ≥5 to \<12 years, ≥12 years), performed using an appropriate Interactive Voice Response System (IVRS), an automated telephone system. The block size will remain confidential. Subjects are considered to have completed the study if they meet all inclusion/exclusion criteria, are considered compliant with study medication, and attend all study visits as defined by the protocol.
Interventions
DRUGRetpamulin Ointment, 1%
Topical retapamulin (SB-275833) ointment, 1% (w/w), and placebo ointment, will be provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse-taper puncture-tip caps. Retapamulin or placebo ointment will be applied twice daily for 5 days.
DRUGLinezolid
Adult and adolescent (=\>12 years of age) subjects will receive one 600mg linezolid tablet (overencapsulated), or one placebo capsule, twice daily for 10 days. Pediatric subjects aged 5-11 years will receive 10mg/kg body weight of a 100mg/5mL oral linezolid suspension, or placebo suspension, twice daily for 10 days. Pediatric subjects \<5 years of age will receive 10mg/kg of a 100mg/5mL oral linezolid suspension, or placebo suspension, three times daily for 10 days.
Sponsors
GlaxoSmithKline
Stiefel, a GSK Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* 2 months of age or older * diagnosis of secondarily-infected traumatic lesion (SITL) or impetigo (bullous or non-bullous) * negative urine pregnancy test (females of childbearing potential) * total skin infection rating scale (SIRS) score of at least 8, which must include a pus/exudate score of at least 3 * subject or parent/legal guardian willing and able to comply with protocol * written informed, dated consent, and written assent (if applicable)
Exclusion criteria
* previous hypersensitivity to pleuromutilins or oxazolidinones * phenylketonuria or known hypersensitivity to aspartame * secondarily-infected animal/human bite, or puncture wound * abscess * chronic ulcerative lesion * underlying skin disease (eg, eczematous dermatitis) with secondary infection * systemic signs and symptoms of infection * skin infection not appropriate for treatment by a topical antibiotic (eg, extensive cellulitis, furunculosis) * subject requires surgical intervention for infection prior to study or likely will during the study * receipt of systemic antibacterial or steroid, or application of any topical therapeutic agent directly to wound within 24 hours of entry into the study * subject currently receiving adrenergic agents * subject currently receiving serotonergic agents * history of pseudomembranous colitis * known, pre-existing myelosuppression, history of myelosuppression with linezolid use, or receiving a medication that produces bone marrow suppression * history of siezures * history of severe renal failure and undergoing dialysis * serious underlying disease that could be imminently life-threatening * pregnant, breast feeding or planning a pregnancy, or not using accepted method of contraception (females of childbearing potential or \<1 year post-menopausal) * use of another investigational drug within 30 days prior to entry into this study * previously enrolled in this study * fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency (for subjects \<12 years of age receiving linezolid suspension)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen | 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at Follow-up | 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid | 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). |
| Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP) | 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid | 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. |
| Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid | 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. |
| Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid | 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. |
| Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP) | 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid | 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. |
| Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid | 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. |
| Number of Participants With Therapeutic Response at Follow-up | 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid | 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. |
| Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19) | 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. |
| Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19) | Lesion sized was measured in centimeters squared at Visits 1, 2, 3, 4, and 5. |
| Number of Participants With the Indicated Clinical Outcome at the End of Therapy | 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 267 |
| 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. | 137 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 |
| Overall Study | Did Not Receive Study Drug | 3 | 3 |
| Overall Study | Investigator Discretion | 2 | 3 |
| Overall Study | Lack of Efficacy | 15 | 3 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Linezolid Plus Placebo Ointment | Total |
|---|---|---|---|
| Age, Continuous | 34.6 Years STANDARD_DEVIATION 21.37 | 33.8 Years STANDARD_DEVIATION 22.38 | 34.3 Years STANDARD_DEVIATION 21.69 |
| Race/Ethnicity, Customized African American/African Heritage | 16 participants | 10 participants | 26 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized Arabic/North African Heritage | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Central/South Asian Heritage | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized East Asian Heritage | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Japanese Heritage | 5 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized South East Asian Heritage | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized White/Caucasian/European | 222 participants | 118 participants | 340 participants |
| Race/Ethnicity, Customized White - Mixed Race | 10 participants | 1 participants | 11 participants |
| Sex: Female, Male Female | 108 Participants | 49 Participants | 157 Participants |
| Sex: Female, Male Male | 159 Participants | 88 Participants | 247 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 267 | 22 / 137 |
| serious Total, serious adverse events | 3 / 267 | 3 / 137 |
Outcome results
Primary
Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen | 41 participants |
| Linezolid Plus Placebo Ointment | Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen | 32 participants |
95% CI: [45.5, 68.4]
95% CI: [72.6, 95.8]
Secondary
Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 0.6 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 0.6 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Total score, Visit 5, n=238, 122 | 1.6 scores on a scale | Standard Deviation 3.92 |
| Linezolid Plus Placebo Ointment | 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 0.8 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pus/exudate, Visit 2, n=265, 135 | 1.4 scores on a scale | Standard Deviation 1.25 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pus/exudate, Visit 3, n=255, 130 | 0.4 scores on a scale | Standard Deviation 0.74 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pus/exudate, Visit 4, n=237, 125 | 0.1 scores on a scale | Standard Deviation 0.34 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pus/exudate, Visit 5, n=238, 122 | 0.0 scores on a scale | Standard Deviation 0.29 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Crusting, Visit 1, n=268, 136 | 2.1 scores on a scale | Standard Deviation 1.49 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Crusting, Visit 2, n=265, 135 | 1.2 scores on a scale | Standard Deviation 1.15 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Crusting, Visit 3, n=255, 130 | 0.8 scores on a scale | Standard Deviation 0.91 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Crusting, Visit 4, n=237, 125 | 0.5 scores on a scale | Standard Deviation 0.83 |
| Linezolid Plus Placebo Ointment | 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 0.73 |
| Linezolid Plus Placebo Ointment | 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 1.08 |
| Linezolid Plus Placebo Ointment | 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 1.26 |
| Linezolid Plus Placebo Ointment | 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 0.73 |
| Linezolid Plus Placebo Ointment | 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 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue warmth, Visit 1, n=268, 136 | 2.6 scores on a scale | Standard Deviation 1.29 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Itching, Visit 3, n=255, 130 | 0.6 scores on a scale | Standard Deviation 1.08 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue warmth, Visit 2, n=265, 135 | 1.3 scores on a scale | Standard Deviation 1.22 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue warmth, Visit 3, n=255, 130 | 0.4 scores on a scale | Standard Deviation 0.69 |
| Linezolid Plus Placebo Ointment | 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 0.34 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue warmth, Visit 5, n=238, 122 | 0.0 scores on a scale | Standard Deviation 0.2 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue edema, Visit 1, n=268, 136 | 2.7 scores on a scale | Standard Deviation 1.3 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue edema, Visit 2, n=265, 135 | 1.5 scores on a scale | Standard Deviation 1.19 |
| Linezolid Plus Placebo Ointment | 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 0.86 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Tissue edema, Visit 4, n=237, 125 | 0.2 scores on a scale | Standard Deviation 0.55 |
| Linezolid Plus Placebo Ointment | 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 0.36 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Itching, Visit 1, n=268, 136 | 1.8 scores on a scale | Standard Deviation 1.51 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Itching, Visit 2, n=265, 135 | 0.9 scores on a scale | Standard Deviation 1.11 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Itching, Visit 4, n=237, 125 | 0.4 scores on a scale | Standard Deviation 0.76 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Itching, Visit 5, n=238, 122 | 0.2 scores on a scale | Standard Deviation 0.66 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pain, Visit 1, n=268, 136 | 3.0 scores on a scale | Standard Deviation 1.65 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pain, Visit 2, n=265, 135 | 1.2 scores on a scale | Standard Deviation 1.39 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pain, Visit 3, n=255, 130 | 0.4 scores on a scale | Standard Deviation 0.96 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Pain, Visit 4, n=237, 125 | 0.1 scores on a scale | Standard Deviation 0.56 |
| Linezolid Plus Placebo Ointment | 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 0.45 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Total score, Visit 1, n=268, 136 | 19.2 scores on a scale | Standard Deviation 5.56 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Total score, Visit 2, n=265, 135 | 9.7 scores on a scale | Standard Deviation 6.32 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Total score, Visit 3, n=255, 130 | 4.1 scores on a scale | Standard Deviation 4.16 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | Total score, Visit 4, n=237, 125 | 2.5 scores on a scale | Standard Deviation 4.13 |
| Linezolid Plus Placebo Ointment | Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5 | E/I, Visit 3, n=255, 130 | 1.0 scores on a scale | Standard Deviation 0.93 |
Secondary
Mean Wound Size at Visits 1, 2, 3, 4, and 5
Lesion sized was measured in centimeters squared at Visits 1, 2, 3, 4, and 5.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Linezolid Plus Placebo Ointment | Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visit 5, n=237, 122 | 0.588 centimeters squared (cm^2) | Standard Deviation 3.3623 |
| Linezolid Plus Placebo Ointment | Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visit 1, n=268, 136 | 5.620 centimeters squared (cm^2) | Standard Deviation 9.6215 |
| Linezolid Plus Placebo Ointment | Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visit 2, n=265, 135 | 4.115 centimeters squared (cm^2) | Standard Deviation 9.4305 |
| Linezolid Plus Placebo Ointment | Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visit 4, n=237, 125 | 0.812 centimeters squared (cm^2) | Standard Deviation 3.4217 |
| Linezolid Plus Placebo Ointment | Mean Wound Size at Visits 1, 2, 3, 4, and 5 | Visit 3, n=255, 130 | 1.776 centimeters squared (cm^2) | Standard Deviation 6.7537 |
Secondary
Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy
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.
Time frame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
Population: ITTB Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Eradication | 2 pathogens |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed eradication | 63 pathogens |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed improvement | 120 pathogens |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Persistence | 7 pathogens |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed persistence | 9 pathogens |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Unable to determine | 1 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed persistence | 1 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Eradication | 1 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Persistence | 1 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed eradication | 70 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Unable to determine | 0 pathogens |
| Linezolid Plus Placebo Ointment | Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy | Presumed improvement | 21 pathogens |
Secondary
Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP) | 41 participants |
| Linezolid Plus Placebo Ointment | Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP) | 32 participants |
Secondary
Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP) | 100 participants |
| Linezolid Plus Placebo Ointment | Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP) | 65 participants |
Secondary
Number of Participants With Clinical Response at Follow-up
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With Clinical Response at Follow-up | 161 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With Clinical Response at Follow-up | 112 participants |
Secondary
Number of Participants With the Indicated Clinical Outcome at the End of Therapy
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical success | 92 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical improvement | 155 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical failure | 16 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Unable to determine | 5 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Unable to determine | 2 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical success | 96 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical failure | 4 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy | Clinical improvement | 34 participants |
Secondary
Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen
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.
Time frame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
Population: ITTMRSA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical improvement | 42 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical failure | 8 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical success | 20 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical failure | 1 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical improvement | 9 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Clinical success | 28 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen | Unable to determine | 0 participants |
Secondary
Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen
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.
Time frame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
Population: ITTMRSA Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Eradication | 1 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Persistence | 4 participants |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | 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 |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Presumed persistence | 0 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Eradication | 0 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Persistence | 1 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Presumed eradication | 28 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Unable to determine | 0 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen | Presumed improvement | 9 participants |
Secondary
Number of Participants With Therapeutic Response at Follow-up
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.
Time frame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
Population: ITTB Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retapamulin Ointment, 1% (Weight/Weight) Plus Oral Placebo | Number of Participants With Therapeutic Response at Follow-up | 100 participants |
| Linezolid Plus Placebo Ointment | Number of Participants With Therapeutic Response at Follow-up | 65 participants |