Skin Infection
Conditions
Keywords
cABSSSI, MRSA
Brief summary
Primary Objective: To make a preliminary assessment of the efficacy of CG400549 (960 mg daily) in subjects with cABSSSI (major cutaneous abscesses) due to MRSA. Secondary Objective(s): * To assess the pharmacokinetics of CG400549 (960 mg daily) in subjects with cABSSSI due to MRSA * To explore the in vitro susceptibility of cABSSSI-related bacteria to CG400549. * To assess the safety of multiple doses of CG400459
Detailed description
This will be an open-label, exploratory study to evaluate the safety, pharmacokinetics, and efficacy of CG400549, daily for 10 to 14 days, in subjects with cABSSSI (major cutaneous abscesses) due to MRSA. All subjects will receive active treatment. Subjects will begin study treatment upon confirmation of clinical eligibility (ie, confirmation of MRSA infection is not required pretreatment). Subjects who begin treatment with CG400549 and are subsequently not found to have S. aureus infection will be discontinued from study treatment, treated as appropriate for the identified pathogen(s), and followed for safety. These subjects will be included in the safety analyses but not in the primary efficacy analysis.
Interventions
DRUGCG400549
960mg QD at fed state approx 1 hour after meal
Sponsors
CrystalGenomics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of major cutaneous abscess suspected or confirmed to be caused by a MRSA. 2. Signs and symptoms should include at least 2 of the following: purulent drainage or discharge, erythema, fluctuance, heat or localized warmth, edema/induration, pain or tenderness to palpation
Exclusion criteria
1. Prior systemic or topical antibacterial therapy 2. Severe sepsis or refractory shock
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Status of Subject's Clinical Responses | Early Clinical Evaluation (ECE, 48 to 72 hours after enrollment) | Stable/improving infection, as defined by the Investigator assessment, was defined as cessation of the spread of the redness, edema, and/or induration of the lesion or reduction in the size (length, width, and shortest distance from the peripheral margin of the abscess) of redness, edema, and/or induration and absence of fever (\< 37.7 °C) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Status of Subject's Clinical Response | End of Treatment (EOT, 10-14 days after beginning treatment) and Test of Cure (TOC, 21-28 days after beginning treatment) | 1. Clinical cure was defined as absence of fever (\< 37.7°C); presence of granulation or wound healing; resolution of pain; and decreased or resolved erythema, edema,induration, and color. Ulceration could persist, but lesions had to appear non-infected to be defined as clinical cure. 2. Clinical improvement was defined as moderate resolution of 2 or more clinical symptoms. 3. clinical failure was defined as persistence or progression of baseline signs and symptoms of cABSSSI, development of new signs and symptoms consistent with Gram-positive infection, or inability to complete the study because of AEs |
| Status of Subject's Microbial Eradication Response | End of Treatment (EOT, 10-14 days after beginning treatment) and Test of Cure (TOC, 21-28 days after beginning treatment) | 1. Microbial eradication was defined by culture (complete absence of all infecting organisms identified at baseline) or presumed because of an absence of clinical symptoms. 2. Microbiological Persistence was defined as the presence of one or more of the original infecting organisms on the TOC culture or as the absence of cultures in case of clinical failure. 3. Microbiological Recurrence was defined as the presence on the final culture of an original infecting organism whose eradication had been either documented or presumed a the end of therapy. |
| Overall Summary of Adverse Events | From time of signing the informed consent to Test of Cure (TOC, 21-28 days after after beginning treatment) | Treatment-Emergent Adverse Event (TEAE) are those that 1. Emerging during treatment, having been absent pre-treatment or 2. Reemerge during treatment, having been present at baseline but stopped prior to treatment or 3. Worsen in severity during treatment relative to the pre-treatment state, when the adverse event is continuous. |
| Mean Plasma Concentration-time Profile of CG400549 | Day 1 predose, Day 1 1hour, Day 1 2hour, Day 1 4hour | The concentrations of CG400549 in plasma collected at each point were analyzed and calculated for its mean plasma concentration. |
Countries
United States
Participant flow
Recruitment details
Subjects with complicated acute bacterial skin and skin structure infection were recruited. Study was conducted from June 2012 to October 2012 at 1 site in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Subjects Received CG400549, MITT All enrolled subjects who received any amount of study drug and was equivalent to the safety population. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | culture negative for MRSA at baseline | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | positive for hepatitis C virus | 1 |
| Overall Study | secondary cellulitis | 1 |
Baseline characteristics
| Characteristic | Subjects Received CG400549, MITT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 35.2 years STANDARD_DEVIATION 13.27 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 11 | 13 / 20 |
| serious Total, serious adverse events | 0 / 11 | 0 / 20 |
Outcome results
Primary
Status of Subject's Clinical Responses
Stable/improving infection, as defined by the Investigator assessment, was defined as cessation of the spread of the redness, edema, and/or induration of the lesion or reduction in the size (length, width, and shortest distance from the peripheral margin of the abscess) of redness, edema, and/or induration and absence of fever (\< 37.7 °C)
Time frame: Early Clinical Evaluation (ECE, 48 to 72 hours after enrollment)
Population: Among 20 participated subjects, 11 subjects had confirmed MRSA and qualified for the mMITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Responses | Stable/ Improving Infection | 10 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Responses | No Stable/ Improving Infection | 1 participants |
Secondary
Mean Plasma Concentration-time Profile of CG400549
The concentrations of CG400549 in plasma collected at each point were analyzed and calculated for its mean plasma concentration.
Time frame: Day 1 predose, Day 1 1hour, Day 1 2hour, Day 1 4hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects Proven MRSA, mMITT | Mean Plasma Concentration-time Profile of CG400549 | Day 1 predose | 32.921 ng/mL | Standard Deviation 101.5 |
| Subjects Proven MRSA, mMITT | Mean Plasma Concentration-time Profile of CG400549 | Day 1 1hour | 426.921 ng/mL | Standard Deviation 488.5 |
| Subjects Proven MRSA, mMITT | Mean Plasma Concentration-time Profile of CG400549 | Day 1 2hour | 1,366.159 ng/mL | Standard Deviation 1028.8 |
| Subjects Proven MRSA, mMITT | Mean Plasma Concentration-time Profile of CG400549 | Day 1 4hour | 1,618.997 ng/mL | Standard Deviation 782.3 |
Secondary
Overall Summary of Adverse Events
Treatment-Emergent Adverse Event (TEAE) are those that 1. Emerging during treatment, having been absent pre-treatment or 2. Reemerge during treatment, having been present at baseline but stopped prior to treatment or 3. Worsen in severity during treatment relative to the pre-treatment state, when the adverse event is continuous.
Time frame: From time of signing the informed consent to Test of Cure (TOC, 21-28 days after after beginning treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Treatment-Related TEAE | 7 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | TEAE with outcome of death | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Severe TEAE | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | TEAE leading to withdrawal of study medic | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Severe Treatment-Related TEAE | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Serious Adverse Event | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Treatment-Emergent Adverse Event (TEAE) | 13 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Serious Adverse Event | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Treatment-Emergent Adverse Event (TEAE) | 10 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Severe TEAE | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Treatment-Related TEAE | 5 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | Severe Treatment-Related TEAE | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | TEAE with outcome of death | 0 participants |
| Subjects Proven MRSA, mMITT | Overall Summary of Adverse Events | TEAE leading to withdrawal of study medic | 0 participants |
Secondary
Status of Subject's Clinical Response
1. Clinical cure was defined as absence of fever (\< 37.7°C); presence of granulation or wound healing; resolution of pain; and decreased or resolved erythema, edema,induration, and color. Ulceration could persist, but lesions had to appear non-infected to be defined as clinical cure. 2. Clinical improvement was defined as moderate resolution of 2 or more clinical symptoms. 3. clinical failure was defined as persistence or progression of baseline signs and symptoms of cABSSSI, development of new signs and symptoms consistent with Gram-positive infection, or inability to complete the study because of AEs
Time frame: End of Treatment (EOT, 10-14 days after beginning treatment) and Test of Cure (TOC, 21-28 days after beginning treatment)
Population: Among 11 mMITT population who had proven MRSA , 2 subjects had major protocol violations, yielding 9 subjects for CE population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Cure at EOT | 8 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Improvement at EOT | 1 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Failure at EOT | 0 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Cure at TOC | 9 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Improvement at TOC | 0 participants |
| Subjects Proven MRSA, mMITT | Status of Subject's Clinical Response | Clinical Failure at TOC | 0 participants |
Secondary
Status of Subject's Microbial Eradication Response
1. Microbial eradication was defined by culture (complete absence of all infecting organisms identified at baseline) or presumed because of an absence of clinical symptoms. 2. Microbiological Persistence was defined as the presence of one or more of the original infecting organisms on the TOC culture or as the absence of cultures in case of clinical failure. 3. Microbiological Recurrence was defined as the presence on the final culture of an original infecting organism whose eradication had been either documented or presumed a the end of therapy.
Time frame: End of Treatment (EOT, 10-14 days after beginning treatment) and Test of Cure (TOC, 21-28 days after beginning treatment)
Population: The ME group was not analyzed because the appropriate post-treatment skin culture data were not accessible due to the improvement of infected lesion.