Skin Diseases, Bacterial, Skin Diseases, Infectious
Conditions
Keywords
Skin, Infection, Complicated Skin and Skin Structure Infection
Brief summary
The purpose of the study is to determine the oral dosage of TR-701 to be used in Phase III studies in patients with complicated skin and skin structure infections.
Interventions
DRUGTR-701 200 mg
oral TR-701 200 mg for 5 to 7 days
DRUGTR-701 300 mg
oral TR-701 300 mg for 5 to 7 days
DRUGTR-701 400 mg
TR-701 400 mg for 5 to 7 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 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with complicated skin and skin structure infection with at least 2 signs and symptoms * Suspected or confirmed infection due to a gram-positive organism
Exclusion criteria
* Complicated skin and skin structure infection due to gram-negative organisms * Complicated skin and skin structure infections requiring more than 7 days of therapy * Uncontrolled diabetes * Chronic systemic immunosuppressive therapy * AIDS with CD4 count \< 200 cells/mm3 * Uncontrolled hypertension * Mild moderate or severe renal failure * Severe hepatic disease * Neutropenia * Use of antidepressants such as SSRIs or MAOIs for 14 days before first dose of study drug * Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set | 7 to 14 days after the last dose of study drug | Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required. |
| Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set | 7-14 days after last dose of study drug | Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set | 21 to 28 days after the last study drug | Persistent clinical cure was defined as continuing favorable response. |
| To Evaluate the Safety Profile of Tedizolid Phosphate | Multiple | — |
| Response Rate at End of Therapy | last day of study treatment | Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required. |
| Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set | 21-28 days after last study drug | — |
| Population PK | Multiple | — |
| Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set | 7-14 days after last dose of study drug | Satisfactory microbiological outcomes are eradication and presumed eradication |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TR-701 200 mg Oral TR-701 200 mg once daily for 5 to 7 days | 63 |
| TR-701 300 mg Oral TR-701 300 mg once daily for 5 to 7 days | 63 |
| TR-701 400 mg Oral TR-701 400 mg once daily for 5 to 7 days | 62 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Bacteremia | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 6 | 3 | 6 |
| Overall Study | Randomized but didn't receive drug | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | TR-701 200 mg | TR-701 300 mg | TR-701 400 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 12.1 | 36.0 years STANDARD_DEVIATION 12.4 | 35.8 years STANDARD_DEVIATION 12 | 36.4 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 20 Participants | 24 Participants | 22 Participants | 66 Participants |
| Sex: Female, Male Male | 43 Participants | 39 Participants | 40 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 63 | 44 / 63 | 43 / 62 |
| serious Total, serious adverse events | 2 / 63 | 1 / 63 | 2 / 62 |
Outcome results
Primary
Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set
Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.
Time frame: 7 to 14 days after the last dose of study drug
Population: The Clinically Evaluable analysis set includes data from all participants who had a diagnosis of cSSSI, received minimal study therapy, completed an assessment, and had no confounding events or factors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set | 98.2 Percentage of participants |
| TR-701 300 mg | Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set | 94.4 Percentage of participants |
| TR-701 400 mg | Clinical Response Rate at Test of Cure in the Clinically Evaluable Analysis Set | 94.4 Percentage of participants |
Primary
Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set
Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.
Time frame: 7-14 days after last dose of study drug
Population: The clinically modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set | 88.9 Percentage of participants |
| TR-701 300 mg | Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set | 88.9 Percentage of participants |
| TR-701 400 mg | Clinical Response Rate at Test of Cure in the Clinical Modified Intent to Treat Analysis Set | 85.5 Percentage of participants |
Secondary
Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set
Persistent clinical cure was defined as continuing favorable response.
Time frame: 21 to 28 days after the last study drug
Population: The clinical modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection. Microbiological samples not available from all participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set | 96.4 Percentage of Participants |
| TR-701 300 mg | Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set | 98.2 Percentage of Participants |
| TR-701 400 mg | Clinical Outcome at the Late Follow-up Visit in the Clinical Modified Intent to Treat Analysis Set | 98.1 Percentage of Participants |
Secondary
Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set
Time frame: 21-28 days after last study drug
Population: The clinical modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection. Microbiological samples not available from all participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set | 0 Percentage of participants |
| TR-701 300 mg | Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set | 0 Percentage of participants |
| TR-701 400 mg | Microbiological Recurrence at Late Follow-up in Clinical Modified Intent to Treat Analysis Set | 0 Percentage of participants |
Secondary
Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set
Satisfactory microbiological outcomes are eradication and presumed eradication
Time frame: 7-14 days after last dose of study drug
Population: The microbiologically evaluable analysis set includes all participants who received study drug, had a diagnosis of complicated skin and skin structure infection, completed an assessment, had no confounding events or factors, and had a baseline Gram-positive bacterial pathogen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set | 100 Percentage of participants |
| TR-701 300 mg | Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set | 93.2 Percentage of participants |
| TR-701 400 mg | Microbiological Response Rate at Test of Cure in the Microbiologically Evaluable Analysis Set | 100 Percentage of participants |
Secondary
Population PK
Time frame: Multiple
Secondary
Response Rate at End of Therapy
Clinical response was defined as resolution or improvement of signs and symptoms of the complicated skin and skin structure infection so that no further antibiotic therapy was required.
Time frame: last day of study treatment
Population: The clinical modified intent to treat analysis set includes data from all participants who received study drug and had a diagnosis of complicated skin and skin structure infection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TR-701 200 mg | Response Rate at End of Therapy | 93.7 Percentage of participants |
| TR-701 300 mg | Response Rate at End of Therapy | 90.5 Percentage of participants |
| TR-701 400 mg | Response Rate at End of Therapy | 91.9 Percentage of participants |
Secondary
To Evaluate the Safety Profile of Tedizolid Phosphate
Time frame: Multiple