Title

Safety and Efficacy Study of TG-873870 (Nemonoxacin) in Diabetic Foot Infections
An Open-Label, Single-Arm, Multi-Center Study of TG-873870 for Treating Patients With Diabetic Foot Infections of Mild to Moderate Severity Associated With Gram-Positive Pathogens
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    tg-873870 ...
  • Study Participants

    40
Safety and Efficacy Study of TG-873870 (Nemonoxacin) in Diabetic Foot Infections
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.
Study Started
Jun 30
2008
Primary Completion
Apr 30
2009
Study Completion
Jun 30
2009
Results Posted
Jan 09
2015
Estimate
Last Update
Jan 09
2015
Estimate

Drug TG-873870 (Nemonoxacin)

750 mg

Nemonoxacin Other

Nemonoxacin 750 mg,oral administration, single-arm, once daily 7±1 and 14±1 days.

Criteria

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

Summary

Nemonoxacin

All Events

Event Type Organ System Event Term Nemonoxacin

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.

Nemonoxacin

95.7
percentage of participants
95% Confidence Interval: 78.1 to 99.9

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

Nemonoxacin (ITT Population at Test of Cure Visit)

82.6
percentage of participants
95% Confidence Interval: 61.2 to 95.0

Nemonoxacin (PP Population at Test of Cure Visit)

89.5
percentage of participants
95% Confidence Interval: 66.9 to 98.7

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.

Nemonoxacin

94.7
percentage of participants
95% Confidence Interval: 74.0 to 99.9

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.

Nemonoxacin (ITT Population at EOT/ET)

100.0
percentage of participants
95% Confidence Interval: 87.7 to 100.0

Nemonoxacin (PP Population at EOT/ET)

100.0
percentage of participants
95% Confidence Interval: 85.2 to 100.0

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.

Nemonoxacin (ITT Population at Test of Cure Visit)

Enterococcus faecalis (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Escherichia coli (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 54.1 to 100.0

Staphylococcus aureus

100.0
percentage of participants
95% Confidence Interval: 78.2 to 100.0

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 29.2 to 100.0

Streptococcus pyogenes (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Nemonoxacin (PP Population at Test of Cure Visit)

Enterococcus faecalis (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Escherichia coli (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Staphylococcus aureus

100.0
percentage of participants
95% Confidence Interval: 73.5 to 100.0

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 29.2 to 100.0

Streptococcus pyogenes (in ITT population)

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.

Nemonoxacin (ITT Population at EOT/ET)

Enterococcus faecalis (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 47.8 to 100.0

Escherichia coli (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 54.1 to 100.0

Staphylococcus aureus (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 81.5 to 100.0

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Streptococcus pyogenes (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Nemonoxacin (PP Population at EOT/ET)

Enterococcus faecalis (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 47.8 to 100.0

Escherichia coli (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Staphylococcus aureus (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 78.2 to 100.0

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 29.2 to 100.0

Streptococcus pyogenes (in ITT population)

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.

Nemonoxacin (ITT Population at Test of Cure Visit)

Enterococcus faecalis (in ITT population)

75.0
percentage of participants
95% Confidence Interval: 19.4 to 99.4

Escherichia coli (in ITT population)

66.7
percentage of participants
95% Confidence Interval: 22.3 to 95.7

Staphylococcus aureus (in ITT population)

93.3
percentage of participants
95% Confidence Interval: 68.1 to 99.8

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 29.2 to 100.0

Streptococcus pyogenes (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 39.8 to 100.0

Nemonoxacin (PP Population at Test of Cure Visit)

Enterococcus faecalis (in ITT population)

75.0
percentage of participants
95% Confidence Interval: 19.4 to 99.4

Escherichia coli (in ITT population)

75.0
percentage of participants
95% Confidence Interval: 19.4 to 99.4

Staphylococcus aureus (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 73.5 to 100.0

Streptococcus agalactiae (in ITT population)

100.0
percentage of participants
95% Confidence Interval: 29.2 to 100.0

Streptococcus pyogenes (in ITT population)

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.

Nemonoxacin (at Baseline, ITT Population)

16.9
scores on a scale (Mean)
Standard Deviation: 6.30

Nemonoxacin (at Test of Cure Visit, ITT Population)

6.0
scores on a scale (Mean)
Standard Deviation: 3.67

Nemonoxacin (Change From Baseline to Test of Cure Visit)

-11.2
scores on a scale (Mean)
Standard Deviation: 6.91

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.

Nemonoxacin (at Baseline, PP Population)

18.2
scores on a scale (Mean)
Standard Deviation: 6.54

Nemonoxacin (at Test of Cure Visit, PP Population)

5.0
scores on a scale (Mean)
Standard Deviation: 2.79

Nemonoxacin (Change From Baseline to Test of Cure Visit)

-12.9
scores on a scale (Mean)
Standard Deviation: 7.10

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.

Nemonoxacin (at Baseline, ITT Population)

16.9
scores on a scale (Mean)
Standard Deviation: 6.30

Nemonoxacin (at EOT/ET Visit, ITT Population)

7.2
scores on a scale (Mean)
Standard Deviation: 4.65

Nemonoxacin (Change From Baseline to EOT/ET Visit)

-9.6
scores on a scale (Mean)
Standard Deviation: 6.35

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.

Nemonoxacin (at Baseline, PP Population)

18.2
scores on a scale (Mean)
Standard Deviation: 6.54

Nemonoxacin (at EOT/ET Visit, PP Population)

6.2
scores on a scale (Mean)
Standard Deviation: 4.31

Nemonoxacin (Change From Baseline to EOT/ET Visit)

-12.1
scores on a scale (Mean)
Standard Deviation: 6.44

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.

Nemonoxacin

Mild to Mild

4.0
participants

Mild to Moderate

Mild to Severe

Mild to Uninfected

8.0
participants

Moderate to Mild

5.0
participants

Moderate to Moderate

3.0
participants

Moderate to Severe

Moderate to Uninfected

12.0
participants

Severe to Mild

Severe to Moderate

Severe to Severe

Severe to Uninfected

Uninfected to Mild

Uninfected to Moderate

Uninfected to Severe

Uninfected to Uninfected

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.

Nemonoxacin

Mild to Mild

2.0
participants

Mild to Moderate

Mild to Severe

Mild to Uninfected

8.0
participants

Moderate to Mild

3.0
participants

Moderate to Moderate

Moderate to Severe

Moderate to Uninfected

15.0
participants

Severe to Mild

Severe to Moderate

Severe to Severe

Severe to Uninfected

Uninfected to Mild

Uninfected to Moderate

Uninfected to Severe

Uninfected to Uninfected

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.

Nemonoxacin

Mild to Mild

1.0
participants

Mild to Moderate

Mild to Severe

Mild to Uninfected

6.0
participants

Moderate to Mild

2.0
participants

Moderate to Moderate

2.0
participants

Moderate to Severe

Moderate to Uninfected

9.0
participants

Severe to Mild

Severe to Moderate

Severe to Severe

Severe to Uninfected

Uninfected to Mild

Uninfected to Moderate

Uninfected to Severe

Uninfected to Uninfected

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.

Nemonoxacin

Mild to Mild

1.0
participants

Mild to Moderate

Mild to Severe

Mild to Uninfected

6.0
participants

Moderate to Mild

1.0
participants

Moderate to Moderate

Moderate to Severe

Moderate to Uninfected

11.0
participants

Severe to Mild

Severe to Moderate

Severe to Severe

Severe to Uninfected

Uninfected to Mild

Uninfected to Moderate

Uninfected to Severe

Uninfected to Uninfected

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.

Nemonoxacin

Hospitalisation Required for DFI During Study

1.0
participants

New or Additional Antibiotic Therapy Required

3.0
participants

Surgery Required for DFI During Study

1.0
participants

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.

Nemonoxacin

Hospitalisation Required for DFI During Study

1.0
participants

New or Additional Antibiotic Therapy Required

3.0
participants

Surgery Required for DFI During Study

1.0
participants

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.

Nemonoxacin

Hospitalisation Required for DFI During Study

New or Additional Antibiotic Therapy Required

Surgery Required for DFI During Study

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.

Nemonoxacin

Hospitalisation Required for DFI During Study

New or Additional Antibiotic Therapy Required

1.0
participants

Surgery Required for DFI During Study

Age, Continuous

59.2
years (Mean)
Standard Deviation: 11.87

Age, Continuous

57.0
years (Median)
Full Range: 39.0 to 87.0

Time Since Diabetes Diagnosis

6.0
years (Median)
Full Range: 0.0 to 23.0

Time Since Diabetes Diagnosis

8.0
years (Mean)
Standard Deviation: 6.49

Age, Customized

Current treatment for Diabetes

Distribution of Time Since Diabetes Diagnosis

HbA1c % Result at Visit 1

Most Recent HbA1c % Result

Race/Ethnicity, Customized

Sex: Female, Male

Type of Diabetes

Overall Study

Nemonoxacin

Drop/Withdrawal Reasons

Nemonoxacin