Skin and Subcutaneous Tissue Bacterial Infections
Conditions
Keywords
ABSSSI, Tedizolid Phosphate, TR-701, Acute Bacterial Skin and Skin Structure Infections
Brief summary
This is a randomized, double-blind, double dummy, multicenter Phase 3 study of oral TR-701 FA 200 mg once daily for 6 days versus oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Approximately 75 to 100 sites globally will participate in this study. Patients with an ABSSSI caused by suspected or documented gram positive pathogen(s) at baseline will be randomized 1:1 to study treatment
Detailed description
The primary objective is to determine the noninferiority in the early clinical response rate of 6 day oral TR-701 FA compared with that of 10-day oral linezolid treatment at the 48-72 Hour Visit in the ITT analysis set in patients with ABSSSI.
Interventions
DRUGTR-701 FA
Oral TR-701 FA 200 mg once daily for six days followed by four days of placebo.
DRUGLinezolid
Oral Linezolid 600 mg twice daily for 10 days
Sponsors
Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with systemic signs of infection diagnosed with acute bacterial skin and skin structure infection (ABSSSI) * Diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections
Exclusion criteria
* Uncomplicated skin infections * Severe sepsis or septic shock * ABSSSI solely due to gram-negative pathogens
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Clinical Response Rate | 48-72 hours | Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit in the Clinically Evaluable-End of Therapy Analysis Sets | EOT Day 11 | Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C |
| Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit | Post-Treatment Evaluation (7-14 days after the End of Therapy) | Clinical success defined as resolution/near resolution of most disease-specific signs and symptoms, absence/near resolution of systemic signs of infection, if present at baseline, no new signs, symptoms, or complications attributable to the ABSSSIs so no further antibiotic therapy was required for the treatment of the primary lesion. |
| To Compare the Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit in the Clinically Evaluable-Post Treatment Evaluation Analysis Set | Post-Treatment Evaluation (7-14 days after the End of Therapy) | Clinical success defined as resolution/near resolution of most disease-specific signs and symptoms, absence/near resolution of systemic signs of infection, no new signs, symptoms, or complications attributable to the ABSSSIs so no further antibiotic therapy was required for the treatment of the primary lesion. |
| Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit. | Day 11 | Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C. |
| Investigator's Assessment of Clinical Response at the Day 7 Visit | Day 7 | Clinical improvement was defined as improvement in overall clinical status. |
| Change From Baseline in Patient-reported Pain, by Study Visit | Multiple | 0=no pain, 10=worst pain Only 1 visit per participant for Day 4-6, only 1 visit for Day 7-9, and only 1 visit for Day 10-13. |
| Investigator's Assessment of Clinical Response at the 48-72 Hour Visit | 48-72 Hour Visit | Clinical improvement was defined as improvement in overall clinical status. |
Countries
Argentina, Brazil, Canada, Czechia, Germany, Hungary, Latvia, Peru, Slovakia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tedizolid Phosphate Oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo | 332 |
| Linezolid Oral linezolid 600 mg twice daily for 10 days | 335 |
| Total | 667 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 22 | 21 |
| Overall Study | Randomized but not treated | 1 | 0 |
| Overall Study | Subject completed only screening and LFU | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 |
Baseline characteristics
| Characteristic | Tedizolid Phosphate | Linezolid | Total |
|---|---|---|---|
| Age, Continuous | 43.6 Years STANDARD_DEVIATION 14.96 | 43.1 Years STANDARD_DEVIATION 15.06 | 43.3 Years STANDARD_DEVIATION 15 |
| Sex: Female, Male Female | 128 Participants | 137 Participants | 265 Participants |
| Sex: Female, Male Male | 204 Participants | 198 Participants | 402 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 331 | 100 / 335 |
| serious Total, serious adverse events | 5 / 331 | 4 / 335 |
Outcome results
Primary
Early Clinical Response Rate
Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C
Time frame: 48-72 hours
Population: The ITT analysis set includes data from all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Early Clinical Response Rate | 264 Responders |
| Linezolid | Early Clinical Response Rate | 266 Responders |
Comparison: The primary objective is to determine the noninferiority in the early clinical response rate of oral tedizolid phosphate compared with that of oral linezolid treatment at the 48-72 Hour Visit in the ITT Analysis Set in patients with ABSSSI.95% CI: [-6.1, 6.2]
Secondary
Change From Baseline in Patient-reported Pain, by Study Visit
0=no pain, 10=worst pain Only 1 visit per participant for Day 4-6, only 1 visit for Day 7-9, and only 1 visit for Day 10-13.
Time frame: Multiple
Population: The Intent to Treat analysis set includes data from all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tedizolid Phosphate | Change From Baseline in Patient-reported Pain, by Study Visit | Day 2 | -1.3 units on a scale | Standard Deviation 2.05 |
| Tedizolid Phosphate | Change From Baseline in Patient-reported Pain, by Study Visit | Day 4-6 | -3.4 units on a scale | Standard Deviation 2.44 |
| Tedizolid Phosphate | Change From Baseline in Patient-reported Pain, by Study Visit | Day 7-9 | -4.5 units on a scale | Standard Deviation 2.71 |
| Tedizolid Phosphate | Change From Baseline in Patient-reported Pain, by Study Visit | Day 10-13 | -5.3 units on a scale | Standard Deviation 2.65 |
| Linezolid | Change From Baseline in Patient-reported Pain, by Study Visit | Day 10-13 | -5.5 units on a scale | Standard Deviation 2.58 |
| Linezolid | Change From Baseline in Patient-reported Pain, by Study Visit | Day 2 | -1.5 units on a scale | Standard Deviation 1.99 |
| Linezolid | Change From Baseline in Patient-reported Pain, by Study Visit | Day 7-9 | -4.6 units on a scale | Standard Deviation 2.67 |
| Linezolid | Change From Baseline in Patient-reported Pain, by Study Visit | Day 4-6 | -3.1 units on a scale | Standard Deviation 2.41 |
Secondary
Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit.
Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C.
Time frame: Day 11
Population: The ITT analysis set includes data from all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit. | 230 participants |
| Linezolid | Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit. | 241 participants |
95% CI: [-9.6, 4.2]
Secondary
Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit in the Clinically Evaluable-End of Therapy Analysis Sets
Responder: No increase in lesion surface area from baseline and oral temperature ≤37.6°C
Time frame: EOT Day 11
Population: All randomized patients receiving minimal study therapy, completed 48-72 Hour and EOT assessments, no concomitant systemic antibiotic therapy through EOT, and had no confounding events or factors
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit in the Clinically Evaluable-End of Therapy Analysis Sets | 219 participants |
| Linezolid | Clinical Response at 48-72 Hours That is Sustained at the End of Therapy Visit in the Clinically Evaluable-End of Therapy Analysis Sets | 232 participants |
95% CI: [-7.7, 5.4]
Secondary
Investigator's Assessment of Clinical Response at the 48-72 Hour Visit
Clinical improvement was defined as improvement in overall clinical status.
Time frame: 48-72 Hour Visit
Population: The Intent to Treat analysis set includes data from all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Investigator's Assessment of Clinical Response at the 48-72 Hour Visit | 299 participants |
| Linezolid | Investigator's Assessment of Clinical Response at the 48-72 Hour Visit | 290 participants |
Comparison: A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the 48-72 Hour Visit using the method of Miettinen and Nurminen with stratification for the presence or absence of fever at baseline.95% CI: [-1.4, 8.5]
Secondary
Investigator's Assessment of Clinical Response at the Day 7 Visit
Clinical improvement was defined as improvement in overall clinical status.
Time frame: Day 7
Population: The Intent to Treat analysis set includes data from all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Investigator's Assessment of Clinical Response at the Day 7 Visit | 302 participants |
| Linezolid | Investigator's Assessment of Clinical Response at the Day 7 Visit | 299 participants |
Comparison: A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the Day 7 Visit using the method of Miettinen and Nurminen with stratification for the presence or absence of fever at baseline.95% CI: [-2.8, 6.4]
Secondary
Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit
Clinical success defined as resolution/near resolution of most disease-specific signs and symptoms, absence/near resolution of systemic signs of infection, if present at baseline, no new signs, symptoms, or complications attributable to the ABSSSIs so no further antibiotic therapy was required for the treatment of the primary lesion.
Time frame: Post-Treatment Evaluation (7-14 days after the End of Therapy)
Population: The Intent to Treat analysis set included data from all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit | 284 participants |
| Linezolid | Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit | 288 participants |
95% CI: [-5.8, 4.9]
Secondary
To Compare the Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit in the Clinically Evaluable-Post Treatment Evaluation Analysis Set
Clinical success defined as resolution/near resolution of most disease-specific signs and symptoms, absence/near resolution of systemic signs of infection, no new signs, symptoms, or complications attributable to the ABSSSIs so no further antibiotic therapy was required for the treatment of the primary lesion.
Time frame: Post-Treatment Evaluation (7-14 days after the End of Therapy)
Population: All randomized patients who received the minimal study therapy, completed EOT and PTE assessments, no concomitant systemic antibiotic therapy through PTE, and had no confounding events or factors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tedizolid Phosphate | To Compare the Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit in the Clinically Evaluable-Post Treatment Evaluation Analysis Set | 264 participants |
| Linezolid | To Compare the Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit in the Clinically Evaluable-Post Treatment Evaluation Analysis Set | 267 participants |
95% CI: [-4.6, 3]