Diabetic Foot Infections
Conditions
Keywords
Diabetic Foot Infections, DFI, Nemonoxacin
Brief summary
Safety and Efficacy Study of TG-873870 (Nemonoxacin) in Diabetic Foot Infections
Detailed description
This study will assess the safety and efficacy of TG-873870 (Nemonoxacin) in patients with Diabetic Foot Infections. Pharmacokinetic (PK) and pharmacodynamic (PD) assessment will be conducted in a subgroup of eight consenting patients.
Interventions
DRUGTG-873870 (Nemonoxacin)
750 mg
Sponsors
TaiGen Biotechnology Co., Ltd.
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
* Body weight ≥ 40 kg * Previously known or newly diagnosed diabetes mellitus, including type 1 and type 2 (per the American Diabetes Association guidelines), which is controlled by proper lifestyle (diet, exercise) or treatment with either oral medications or insulin * Patients' HbA1c ≦ 12% at screening * Clinically defined diabetic foot infection of mild or moderate severity (PEDIS grade 2-3) as based on the guideline of the Infectious Diseases Society of America. It includes any inframalleolar infection of the soft-tissue, such as paronychia, cellulitis, myositis, abscesses, and tendonitis * Evidence of necrotic tissue, purulent collections or abscess that may require excision, incision or drainage (based on investigator's judgment, and a surgeon if needed) * Must be able to provide suitable tissue specimens (preferably obtained by biopsy or tissue curettage, or purulent fluid aspiration, rather than by swabbing) from the infected wound (after appropriate cleansing and debridement) for Gram-staining and bacterial cultures (aerobes and anaerobes) * A confirmed Gram-positive pathogen infection by Gram-stain. The criterion to determine patient's eligibility for study recruitment is a Gram-stained smear with at least 1 Gram-positive organism seen in at least two high power fields. A solely Gram-positive pathogen infection or a polymicrobial infection including Gram-positive and Gram-negative pathogens are acceptable within the framework of the study
Exclusion criteria
* A co-morbid disease condition that could compromise evaluation or participation in this study, such as severe hepatic disease (e.g., active hepatitis, decompensated liver cirrhosis), renal failure (estimated creatinine clearance \[CrCl\] \<30 ml/minute or need for hemodialysis or peritoneal dialysis), or active systemic malignancy (advanced or metastatic), unless enrollment is deemed appropriate at the discretion of the Investigator with prior consultation with the study Medical Monitor * History of prolonged QTc interval or a medical condition requiring the use of a concomitant medication that is associated with an increased QTc interval (e.g., class I or class III anti-arrhythmic agents) * Contact dermatitis over the infected skin area, infected third-degree burn wounds, necrotizing fascitis, extensive gangrene, pyoderma gangrenosum, deep vein thrombosis, shock, or any medical disorder that could either interfere with the evaluation of treatment or the response of the patient to therapy * Radiological evidence of bone or joints infection within 7 days prior to or at screening, i.e. potential osteomyelitis or septic arthritis * Clinically defined uninfected or severe infection (PEDIS grade 1 or 4) as based on the Infectious Diseases Society of America classification system * Any known severe immunosuppressive condition, such as an active hematological malignancy, HIV infection or active treatment with any immunosuppressive drug (including corticosteroids at a dose of \>20 mg/day of prednisone, or its equivalent) * Has received or will be receiving chemotherapy or oncolytics within six months prior to entering or during the study * History of current or active alcohol abuse (\>3 drinks daily or binge drinking) or any illicit drug use * Known or suspected critical ischemia of the affected limb (based on investigators' clinical judgments and vascular assessment) * Wound that contains or is proximate to any prosthetic materials or devices that is/are not scheduled for removal * Patient with a foot infection that, in the investigator's judgment, is severe enough to require hospitalization or intravenous antibiotic therapy * Neutrophil count \<1000 cells/mm3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success (in ITT Population) | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success (in PP Population) | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions. |
| Clinical Success (at End of Treatment/Early Termination) | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions. |
| Per-Pathogen Clinical Responses (at Test of Cure) | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | Clinical responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Clinical Responses were assessed at Test of Cure visit within each of the ITT and PP populations. Insufficient numbers prevented reporting Clinical Success rates for Streptococcus pyogenes in the PP population. |
| Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | Clinical responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Clinical Responses were assessed at at End of Treatment/Early Termination within each of the ITT and PP populations. Insufficient numbers prevented reporting Clinical Success rates for Streptococcus pyogenes in the PP population. |
| Per-Pathogen Microbiological Responses | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | Microbiological responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Microbiological Responses were assessed at Test of Cure visit within each of the ITT and PP populations. Insufficient numbers prevented reporting Microbiological Success rates for Streptococcus pyogenes in the PP population. |
| Total Wound Score (at Test of Cure in ITT Population) | Visit 1 (Baseline); Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively. |
| Total Wound Score (at Test of Cure in PP Population) | Visit 1 (Baseline); Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively. |
| Microbiological Success Rate | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | Microbiological Success * Eradicated, defined as absence of the original pathogen(s) from a repeat culture of the original infection site performed at the TOC visit. * Presumed Eradicated, defined as meeting the definition for Clinical Success at the TOC visit, but tissue sample could be obtained for culture from the original infection site. * TOC=Test of Cure |
| Total Wound Score (at End of Treatment/ Early Termination in PP Population) | Visit 1 (Baseline); End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively. |
| Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and End of Treatment/Early Termination. |
| Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and Test of Cure. |
| Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and End of Treatment/Early Termination. |
| Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination | The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and Test of Cure. |
| Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at End of Treatment/Early Termination. |
| Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at End of Treatment/Early Termination. |
| Total Wound Score (at End of Treatment/ Early Termination in ITT Population) | Visit 1 (Baseline); End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1) | The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and End of Treatment/ Early Termination visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively. |
Countries
South Africa, Taiwan, Thailand, United States
Participant flow
Recruitment details
Patients were assessed during the 1- to 2-day screening phase (Visit 1) to determine their eligibility. Eligible patients demonstrating the presence of at least one Gram-positive organism on the basis of Gram-stain could begin treatment with study medication the same day (Day 1, Visit 1).
Participants by arm
| Arm | Count |
|---|---|
| Nemonoxacin Nemonoxacin 750 mg,oral administration, single-arm, once daily 7±1 and 14±1 days.
TG-873870 (Nemonoxacin): 750 mg | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | CULTURE GRAM NEG SPECIES | 1 |
| Overall Study | CULTURE RESULTS: GRAM-VE | 1 |
| Overall Study | NO GRAM POSITIVE CULTURE GROWN | 1 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Nemonoxacin |
|---|---|
| Age, Continuous | 57.0 years |
| Age, Customized >= 20 and < 30 years | 0 participants |
| Age, Customized < 20 years | 0 participants |
| Age, Customized >= 30 and < 40 years | 1 participants |
| Age, Customized >= 40 and < 50 years | 8 participants |
| Age, Customized >= 50 and < 60 years | 11 participants |
| Age, Customized >= 60 and < 70 years | 3 participants |
| Age, Customized >= 70 and < 80 years | 9 participants |
| Age, Customized >= 80 years | 1 participants |
| Current treatment for Diabetes Diet and Exercise | 20 participants |
| Current treatment for Diabetes Insulin | 16 participants |
| Current treatment for Diabetes Oral Agent | 25 participants |
| Distribution of Time Since Diabetes Diagnosis >= 10 and < 20 years | 9 participants |
| Distribution of Time Since Diabetes Diagnosis >= 20 and < 30 years | 2 participants |
| Distribution of Time Since Diabetes Diagnosis >= 30 and < 40 years | 0 participants |
| Distribution of Time Since Diabetes Diagnosis >= 40 years | 0 participants |
| Distribution of Time Since Diabetes Diagnosis >= 5 and < 10 years | 8 participants |
| Distribution of Time Since Diabetes Diagnosis < 5 years | 12 participants |
| Distribution of Time Since Diabetes Diagnosis Missing | 2 participants |
| HbA1c % Result at Visit 1 >= 10.0% and < 11.0% | 1 participants |
| HbA1c % Result at Visit 1 >= 11.0% and < 12.0% | 2 participants |
| HbA1c % Result at Visit 1 >= 12.0% | 1 participants |
| HbA1c % Result at Visit 1 < 6.5% | 6 participants |
| HbA1c % Result at Visit 1 >= 6.5% and < 7.0% | 2 participants |
| HbA1c % Result at Visit 1 >= 7.0% and < 9.0% | 18 participants |
| HbA1c % Result at Visit 1 >= 9.0% and < 10.0% | 3 participants |
| Most Recent HbA1c % Result >= 10.0% and < 11.0% | 2 participants |
| Most Recent HbA1c % Result >= 11.0% and < 12.0% | 1 participants |
| Most Recent HbA1c % Result >= 12.0% | 0 participants |
| Most Recent HbA1c % Result < 6.5% | 2 participants |
| Most Recent HbA1c % Result >= 6.5% and < 7.0% | 3 participants |
| Most Recent HbA1c % Result >= 7.0% and < 9.0% | 10 participants |
| Most Recent HbA1c % Result >= 9.0% and < 10.0% | 3 participants |
| Most Recent HbA1c % Result Missing | 12 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 5 participants |
| Race/Ethnicity, Customized Black | 7 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 6 participants |
| Race/Ethnicity, Customized White | 15 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 22 Participants |
| Time Since Diabetes Diagnosis | 8.0 years STANDARD_DEVIATION 6.49 |
| Type of Diabetes Type 1 (Juvenile Onset) | 3 participants |
| Type of Diabetes Type 2 (Adult Onset) | 30 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 38 |
| serious Total, serious adverse events | 5 / 38 |
Outcome results
Primary
Clinical Success (in ITT Population)
Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
Population: All eligible patients who took at least one whole dose of study drug and had at least 1 gram-positive pathogen identified at the Baseline Visit (Visit 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemonoxacin | Clinical Success (in ITT Population) | 95.7 percentage of participants |
Secondary
Clinical Success (at End of Treatment/Early Termination)
Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemonoxacin | Clinical Success (at End of Treatment/Early Termination) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Clinical Success (at End of Treatment/Early Termination) | 100.0 percentage of participants |
Secondary
Clinical Success (in PP Population)
Clinical Success * Resolution is defined as total resolution of all pretreatment clinically significant signs and symptoms of infection and no development of any systemic evidence of infection. * Improvement is defined as resolution of more than two, but not all, pretreatment clinical signs and symptoms, or partial resolution of all clinical signs and symptoms relative to the baseline assessment, with no further need for antibiotic therapy, and no need for infection-related surgical interventions.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
Population: All eligible patients who took at least one whole dose of study drug and had at least 1 gram-positive pathogen identified at the Baseline Visit (Visit 1), and adhered to the protocol without major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemonoxacin | Clinical Success (in PP Population) | 94.7 percentage of participants |
Secondary
Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population
The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and End of Treatment/Early Termination.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Mild to Uninfected | 8 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Mild to Mild | 4 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Mild to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Mild to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Severe to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Severe to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Uninfected to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Uninfected to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Uninfected to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Uninfected to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Moderate to Uninfected | 12 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Moderate to Mild | 5 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Moderate to Moderate | 3 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Moderate to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Severe to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in ITT Population | Severe to Mild | 0 participants |
Secondary
Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population
The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and End of Treatment/Early Termination.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Uninfected to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Uninfected to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Uninfected to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Uninfected to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Mild to Uninfected | 6 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Moderate to Moderate | 2 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Moderate to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Severe to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Severe to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Severe to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Severe to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Mild to Mild | 1 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Mild to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Mild to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Moderate to Uninfected | 9 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at End of Treatment/Early Termination in PP Population | Moderate to Mild | 2 participants |
Secondary
Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population
The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and Test of Cure.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Uninfected to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Uninfected to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Mild to Uninfected | 8 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Mild to Mild | 2 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Moderate to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Severe to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Uninfected to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Uninfected to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Mild to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Mild to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Moderate to Uninfected | 15 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Moderate to Mild | 3 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Moderate to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Severe to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Severe to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in ITT Population | Severe to Severe | 0 participants |
Secondary
Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population
The number of patients within each of the PEDIS grading categories (uninfected, mild, moderate and severe) at baseline and Test of Cure.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Uninfected to Uninfected | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Uninfected to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Uninfected to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Severe to Mild | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Severe to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Severe to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Uninfected to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Mild to Uninfected | 6 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Mild to Mild | 1 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Mild to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Mild to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Moderate to Uninfected | 11 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Moderate to Mild | 1 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Moderate to Moderate | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Moderate to Severe | 0 participants |
| Nemonoxacin | Diabetic Foot Assessment (PEDIS) Shifts From Baseline at Test of Cure in PP Population | Severe to Uninfected | 0 participants |
Secondary
Microbiological Success Rate
Microbiological Success * Eradicated, defined as absence of the original pathogen(s) from a repeat culture of the original infection site performed at the TOC visit. * Presumed Eradicated, defined as meeting the definition for Clinical Success at the TOC visit, but tissue sample could be obtained for culture from the original infection site. * TOC=Test of Cure
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemonoxacin | Microbiological Success Rate | 82.6 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Microbiological Success Rate | 89.5 percentage of participants |
Secondary
Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population)
Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at End of Treatment/Early Termination.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
Population: Number at the End of Treatment/Early Termination Visit, ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | New or Additional Antibiotic Therapy Required | 3 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | Surgery Required for DFI During Study | 1 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | Hospitalisation Required for DFI During Study | 1 participants |
Secondary
Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population)
Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at Test of Cure.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
Population: Number at Test of Cure Visit, ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | Surgery Required for DFI During Study | 1 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | Hospitalisation Required for DFI During Study | 1 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in ITT Population) | New or Additional Antibiotic Therapy Required | 3 participants |
Secondary
Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population)
Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at Test of Cure.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | Surgery Required for DFI During Study | 0 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | Hospitalisation Required for DFI During Study | 0 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | New or Additional Antibiotic Therapy Required | 1 participants |
Secondary
Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population)
Results in relation to the need for surgery, hospitalization, new and/or additional non-study antibiotic therapy for failure of initial oral therapy at End of Treatment/Early Termination.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | Surgery Required for DFI During Study | 0 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | Hospitalisation Required for DFI During Study | 0 participants |
| Nemonoxacin | Need for Surgery, Hospitalisation and Non-Study Antibiotic Therapy for Diabetic Foot Infection During Study (in PP Population) | New or Additional Antibiotic Therapy Required | 0 participants |
Secondary
Per-Pathogen Clinical Response (at End of Treatment/Early Termination)
Clinical responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Clinical Responses were assessed at at End of Treatment/Early Termination within each of the ITT and PP populations. Insufficient numbers prevented reporting Clinical Success rates for Streptococcus pyogenes in the PP population.
Time frame: End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Staphylococcus aureus (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Escherichia coli (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Enterococcus faecalis (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Streptococcus pyogenes (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Staphylococcus aureus (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Escherichia coli (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Streptococcus pyogenes (in ITT population) | NA percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Response (at End of Treatment/Early Termination) | Enterococcus faecalis (in ITT population) | 100.0 percentage of participants |
Secondary
Per-Pathogen Clinical Responses (at Test of Cure)
Clinical responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Clinical Responses were assessed at Test of Cure visit within each of the ITT and PP populations. Insufficient numbers prevented reporting Clinical Success rates for Streptococcus pyogenes in the PP population.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Per-Pathogen Clinical Responses (at Test of Cure) | Escherichia coli (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Responses (at Test of Cure) | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Responses (at Test of Cure) | Enterococcus faecalis (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Responses (at Test of Cure) | Streptococcus pyogenes (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Clinical Responses (at Test of Cure) | Staphylococcus aureus | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Responses (at Test of Cure) | Streptococcus pyogenes (in ITT population) | NA percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Responses (at Test of Cure) | Staphylococcus aureus | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Responses (at Test of Cure) | Escherichia coli (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Responses (at Test of Cure) | Enterococcus faecalis (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Clinical Responses (at Test of Cure) | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
Secondary
Per-Pathogen Microbiological Responses
Microbiological responses were assessed on a per-pathogen basis for the most frequently isolated pathogens at baseline (i.e., present in four or more patients), including MRSA. Microbiological Responses were assessed at Test of Cure visit within each of the ITT and PP populations. Insufficient numbers prevented reporting Microbiological Success rates for Streptococcus pyogenes in the PP population.
Time frame: Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nemonoxacin | Per-Pathogen Microbiological Responses | Escherichia coli (in ITT population) | 66.7 percentage of participants |
| Nemonoxacin | Per-Pathogen Microbiological Responses | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Microbiological Responses | Enterococcus faecalis (in ITT population) | 75.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Microbiological Responses | Streptococcus pyogenes (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin | Per-Pathogen Microbiological Responses | Staphylococcus aureus (in ITT population) | 93.3 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Microbiological Responses | Streptococcus pyogenes (in ITT population) | NA percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Microbiological Responses | Staphylococcus aureus (in ITT population) | 100.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Microbiological Responses | Escherichia coli (in ITT population) | 75.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Microbiological Responses | Enterococcus faecalis (in ITT population) | 75.0 percentage of participants |
| Nemonoxacin (PP Population at Test of Cure Visit) | Per-Pathogen Microbiological Responses | Streptococcus agalactiae (in ITT population) | 100.0 percentage of participants |
Secondary
Total Wound Score (at End of Treatment/ Early Termination in ITT Population)
The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and End of Treatment/ Early Termination visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively.
Time frame: Visit 1 (Baseline); End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemonoxacin | Total Wound Score (at End of Treatment/ Early Termination in ITT Population) | 16.9 scores on a scale | Standard Deviation 6.3 |
| Nemonoxacin (PP Population at Test of Cure Visit) | Total Wound Score (at End of Treatment/ Early Termination in ITT Population) | 7.2 scores on a scale | Standard Deviation 4.65 |
| Nemonoxacin (Change From Baseline to Test of Cure Visit) | Total Wound Score (at End of Treatment/ Early Termination in ITT Population) | -9.6 scores on a scale | Standard Deviation 6.35 |
Secondary
Total Wound Score (at End of Treatment/ Early Termination in PP Population)
The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively.
Time frame: Visit 1 (Baseline); End of Treatment/Early Termination Visit; 7±1, 14±1, 21±1 or 28±1 days after Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemonoxacin | Total Wound Score (at End of Treatment/ Early Termination in PP Population) | 18.2 scores on a scale | Standard Deviation 6.54 |
| Nemonoxacin (PP Population at Test of Cure Visit) | Total Wound Score (at End of Treatment/ Early Termination in PP Population) | 6.2 scores on a scale | Standard Deviation 4.31 |
| Nemonoxacin (Change From Baseline to Test of Cure Visit) | Total Wound Score (at End of Treatment/ Early Termination in PP Population) | -12.1 scores on a scale | Standard Deviation 6.44 |
Secondary
Total Wound Score (at Test of Cure in ITT Population)
The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively.
Time frame: Visit 1 (Baseline); Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemonoxacin | Total Wound Score (at Test of Cure in ITT Population) | 16.9 scores on a scale | Standard Deviation 6.3 |
| Nemonoxacin (PP Population at Test of Cure Visit) | Total Wound Score (at Test of Cure in ITT Population) | 6.0 scores on a scale | Standard Deviation 3.67 |
| Nemonoxacin (Change From Baseline to Test of Cure Visit) | Total Wound Score (at Test of Cure in ITT Population) | -11.2 scores on a scale | Standard Deviation 6.91 |
Secondary
Total Wound Score (at Test of Cure in PP Population)
The Diabetic Foot Infection (DFI) Wound Scores will be used to evaluate the wound assessment at baseline and Test of Cure visits. The wound composite score was based on combining the general wound parameters (signs and symptoms of infection), and wound measurements (length, width, depth). Each wound parameter was assigned a score based on severity, with higher scores defining greater severity. For wound measurements and undermining, larger measurements received higher scores. The minimum and maximum score are 3 and 49, respectively.
Time frame: Visit 1 (Baseline); Test of Cure Visit, 12±2 days after End of Treatment Visit/Early Termination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemonoxacin | Total Wound Score (at Test of Cure in PP Population) | 18.2 scores on a scale | Standard Deviation 6.54 |
| Nemonoxacin (PP Population at Test of Cure Visit) | Total Wound Score (at Test of Cure in PP Population) | 5.0 scores on a scale | Standard Deviation 2.79 |
| Nemonoxacin (Change From Baseline to Test of Cure Visit) | Total Wound Score (at Test of Cure in PP Population) | -12.9 scores on a scale | Standard Deviation 7.1 |