Clinical Trials List
Protocol NumberRX-3341-303
2014-02-07 - 2015-07-30
Phase II/III
Terminated7
ICD-10L56.8
Other specified acute skin changes due to ultraviolet radiation
ICD-10T86.822
Skin graft (allograft) (autograft) infection
A Phase 3, multicenter, randomized, double-blind, active controlled study to evaluate the efficacy and safety of IV and oral delafloxacin compared with vancomycin + aztreonam in patients with acute bacterial skin and skin structure infections
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Melinta Therapeutics, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Po-Liang Lu Division of Infectious Disease
- Chung-Hao Huang Division of Infectious Disease
- 賴宗志 Division of Infectious Disease
- Chun-Yu Lin Division of Infectious Disease
- 林蔚如 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yung-Ching Liu Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Ting Chang Division of Infectious Disease
- 湯宏仁 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 李原地 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Fu-Lun Chen Division of Infectious Disease
- Tsong-Yih Ou Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
acute bacterial skin and skin structure infections
Objectives
Primary:
To assess the clinical efficacy of delafloxacin compare with vancomycin+aztreonam in patients with ABSSSIs at 48 to 72 hours after initiation of treatment.
Secondary:
To evaluate the clinical efficacy of delafloxacin compare with vancomycin+aztreonam by assessing the investigator-assessed response of signs and symptoms of infection at the Follow-up Visit
Test Drug
Delafloxacin
Active Ingredient
Delafloxacin
Dosage Form
tablets
Dosage
450mg/300mg
Endpoints
Primary:
Primary Efficacy Endpoints:
FDA Submission: Objective response of >20% reduction in lesion
erythema area compared to baseline at 48 to 72 hours after
initiation of treatment as determined by digital measurements of
the leading edge.
EMA Submission: Investigator-assessed response of signs and
symptoms of infection at the Follow-up Visit.
Secondary Efficacy Endpoints:
FDA Submission:
• Investigator-assessed response of signs and symptoms of
infection at the Follow-up Visit (EMA primary endpoint)
• Investigator-assessed response of signs and symptoms of
infection in patients with a baseline BMI >30 at the
Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection at the Late Follow-up Visit
• Reduction of erythema of >30% at 48 to 72 hours when
digital measurements are used
• Reduction in pain at End of Treatment as measured by
ePRO system
• Microbiological response of eradicated (documented or
presumed) at the Follow-up Visit in all patients
EMA Submission:
• Investigator-assessed response of signs and symptoms of
infection at the Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection in patients with a baseline BMI >30 at the
Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection at the Late Follow-up Visit
• Reduction of erythema of >30% at 48 to 72 hours when
digital measurements are used
• Reduction in pain as measured by ePRO system
• Objective response based on >20% reduction in lesion
erythema area compared to baseline at 48 to 72 hours after
initiation of treatment as determined by digital
measurements of the leading edge (FDA primary
endpoint)
Primary Efficacy Endpoints:
FDA Submission: Objective response of >20% reduction in lesion
erythema area compared to baseline at 48 to 72 hours after
initiation of treatment as determined by digital measurements of
the leading edge.
EMA Submission: Investigator-assessed response of signs and
symptoms of infection at the Follow-up Visit.
Secondary Efficacy Endpoints:
FDA Submission:
• Investigator-assessed response of signs and symptoms of
infection at the Follow-up Visit (EMA primary endpoint)
• Investigator-assessed response of signs and symptoms of
infection in patients with a baseline BMI >30 at the
Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection at the Late Follow-up Visit
• Reduction of erythema of >30% at 48 to 72 hours when
digital measurements are used
• Reduction in pain at End of Treatment as measured by
ePRO system
• Microbiological response of eradicated (documented or
presumed) at the Follow-up Visit in all patients
EMA Submission:
• Investigator-assessed response of signs and symptoms of
infection at the Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection in patients with a baseline BMI >30 at the
Follow-up Visit
• Investigator-assessed response of signs and symptoms of
infection at the Late Follow-up Visit
• Reduction of erythema of >30% at 48 to 72 hours when
digital measurements are used
• Reduction in pain as measured by ePRO system
• Objective response based on >20% reduction in lesion
erythema area compared to baseline at 48 to 72 hours after
initiation of treatment as determined by digital
measurements of the leading edge (FDA primary
endpoint)
Inclution Criteria
1. Adult (≥18 years of age) men or women. (The subject participating in this study in Taiwan must be
over 20 years of age)
2. Patients must have a diagnosis of ABSSSI, ie, an infection involving skin and/or subcutaneous tissues
of at least one of the following 4 types (only the primary infection type will be followed for study
purposes):
Cellulitis/erysipelas: A diffuse skin infection characterized by spreading areas of redness of a
minimum surface area of 75 cm2
as determined by measurement of the longest head-to-toe length
(the longest dimension of the infection) multiplied by the longest perpendicular width using a
disposable ruler
Wound infection: An infection characterized by purulent drainage from a traumatic or surgical
wound with surrounding redness of a minimum surface area of 75 cm2
(eg, the shortest distance of
redness extending at least 5 cm from the peripheral margin of the wound) as determined by
measurement of the longest head-to-toe length (the longest dimension of the infection) multiplied
by the longest perpendicular width using a disposable ruler
Major cutaneous abscess: An infection characterized by a collection of pus within the dermis or
deeper that is accompanied by redness of a minimum surface area of 75 cm2
(eg, the shortest
distance of redness extending at least 5 cm from the peripheral margin of the abscess) as
determined by measurement of the longest head-to-toe length (the longest dimension of the
infection) multiplied by the longest perpendicular width using a disposable ruler
Burn infection: An infection characterized by purulent drainage that is accompanied by redness of
a minimum surface area of 75 cm2
(eg, the shortest distance of redness extending at least 5 cm
from the peripheral margin of the burn infection) as determined by measurement of the longest
head-to-toe length (the longest dimension of the infection) multiplied by the longest perpendicular
width using a disposable ruler. Patients with burn infections may only be enrolled if the area of the
burn comprises ≤10% of the patient’s body surface as determined by the investigator
3. Patients must have at least two of the following signs of systemic infection:
Lymph node enlargement due to the present infection
Documented fever ≥38°C/100.4°F (or the equivalent value for the temperature recording method
used)
Lymphangitis
Elevated white blood cells of ≥10,000 cells/µL in the 48 hours prior to first dose of study drug
Elevated C-reactive protein (>10 × upper limit of normal [ULN]) in the 48 hours prior to first dose
of study drug
Purulent or seropurulent drainage or discharge
4. In the opinion of the investigator, the patient must be a suitable candidate for IV antibiotic therapy.
5. Sexually active women and men with partners of childbearing potential must agree to use an
acceptable form of contraception, as determined by the investigator (eg, abstinence, oral
contraceptives, double-barrier methods, hormonal injectable, transdermal, or implanted
contraceptives, tubal ligation, or vasectomy), during participation in the study and for 30 days after
the final dose of study drug.
6. Female partners of male patients should also use an additional reliable method of contraception, such
as spermicide with male or female condoms, cervical sponge, intrauterine device, cervical cap or
diaphragm, or oral, implantable, transdermal, or injectable contraceptives during study and for
30 days after the final dose of study drug.
7. In the opinion of the investigator, the patient must be able and willing to comply with protocol
requirements.
8. A written, voluntarily signed informed consent must be obtained from the patient or legally
authorized representative, in accordance with local regulations, before the initiation of any
study-related procedures. The patient or legally authorized representative must be able to read and/or
understand the informed consent form (ICF) as required by the legal jurisdiction and the institutional
review board/independent ethics committee (IRB/IEC) where the patient is treated.
over 20 years of age)
2. Patients must have a diagnosis of ABSSSI, ie, an infection involving skin and/or subcutaneous tissues
of at least one of the following 4 types (only the primary infection type will be followed for study
purposes):
Cellulitis/erysipelas: A diffuse skin infection characterized by spreading areas of redness of a
minimum surface area of 75 cm2
as determined by measurement of the longest head-to-toe length
(the longest dimension of the infection) multiplied by the longest perpendicular width using a
disposable ruler
Wound infection: An infection characterized by purulent drainage from a traumatic or surgical
wound with surrounding redness of a minimum surface area of 75 cm2
(eg, the shortest distance of
redness extending at least 5 cm from the peripheral margin of the wound) as determined by
measurement of the longest head-to-toe length (the longest dimension of the infection) multiplied
by the longest perpendicular width using a disposable ruler
Major cutaneous abscess: An infection characterized by a collection of pus within the dermis or
deeper that is accompanied by redness of a minimum surface area of 75 cm2
(eg, the shortest
distance of redness extending at least 5 cm from the peripheral margin of the abscess) as
determined by measurement of the longest head-to-toe length (the longest dimension of the
infection) multiplied by the longest perpendicular width using a disposable ruler
Burn infection: An infection characterized by purulent drainage that is accompanied by redness of
a minimum surface area of 75 cm2
(eg, the shortest distance of redness extending at least 5 cm
from the peripheral margin of the burn infection) as determined by measurement of the longest
head-to-toe length (the longest dimension of the infection) multiplied by the longest perpendicular
width using a disposable ruler. Patients with burn infections may only be enrolled if the area of the
burn comprises ≤10% of the patient’s body surface as determined by the investigator
3. Patients must have at least two of the following signs of systemic infection:
Lymph node enlargement due to the present infection
Documented fever ≥38°C/100.4°F (or the equivalent value for the temperature recording method
used)
Lymphangitis
Elevated white blood cells of ≥10,000 cells/µL in the 48 hours prior to first dose of study drug
Elevated C-reactive protein (>10 × upper limit of normal [ULN]) in the 48 hours prior to first dose
of study drug
Purulent or seropurulent drainage or discharge
4. In the opinion of the investigator, the patient must be a suitable candidate for IV antibiotic therapy.
5. Sexually active women and men with partners of childbearing potential must agree to use an
acceptable form of contraception, as determined by the investigator (eg, abstinence, oral
contraceptives, double-barrier methods, hormonal injectable, transdermal, or implanted
contraceptives, tubal ligation, or vasectomy), during participation in the study and for 30 days after
the final dose of study drug.
6. Female partners of male patients should also use an additional reliable method of contraception, such
as spermicide with male or female condoms, cervical sponge, intrauterine device, cervical cap or
diaphragm, or oral, implantable, transdermal, or injectable contraceptives during study and for
30 days after the final dose of study drug.
7. In the opinion of the investigator, the patient must be able and willing to comply with protocol
requirements.
8. A written, voluntarily signed informed consent must be obtained from the patient or legally
authorized representative, in accordance with local regulations, before the initiation of any
study-related procedures. The patient or legally authorized representative must be able to read and/or
understand the informed consent form (ICF) as required by the legal jurisdiction and the institutional
review board/independent ethics committee (IRB/IEC) where the patient is treated.
Exclusion Criteria
1. Medical history of significant hypersensitivity or allergic reaction to quinolones, beta-lactams,
vancomycin, or vancomycin derivatives according to the judgment of the investigator.
2. Women who are pregnant or lactating.
3. Any chronic or underlying skin condition at the site of infection that may complicate the assessment
of response (eg, atopic dermatitis or eczema). Any other skin condition that, in the opinion of the
investigator, would interfere with objective measurement of the ABSSSI under treatment.
4. Infection associated with a prosthetic joint or the removal of a prosthetic joint, or infection involving
other prosthetic materials or foreign bodies (eg, catheter tunnels) unless that other prosthetic material
will be removed within 24 hours after starting study drug.
5. Infection associated with any of the following:
Human or animal bite (insect bites are not considered animal bites)
Osteomyelitis
Decubitus ulcer
Diabetic foot ulcer
Septic arthritis
Mediastinitis
Sternal wound
Necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis
Myositis
Tendinitis
Endocarditis
Toxic shock syndrome
Sustained shock (blood pressure <90 mm Hg for >2 hours despite adequate fluid resuscitation, with
evidence of hypoperfusion or use of sympathomimetic agents to maintain blood pressure)
Gangrene or gas gangrene
Burns covering 10% of body surface area
Severely impaired arterial blood supply to an extremity with an ABSSSI (a patient with a palpable
distal pulse or an audible distal pulse by Doppler may be enrolled)
Current evidence of deep vein thrombosis or superficial thrombophlebitis
Any infection types with poor circulatory status in the opinion of the investigator
6. Minor abscesses, unless present with 1 of the 4 acceptable types of ABSSSIs noted in inclusion
criteria.
7. Any infection expected to require other systemic antibacterial agents in addition to study drug.
8. Receipt of systemic antibiotic therapy in the 14 days before enrollment unless one of the following is
documented:
The patient received at least 48 hours of antibiotic therapy for ABSSSI AND the clinic notes or
photographs document the clinical progression of ABSSSI (ie, not by patient history alone)
The patient recently (within 14 days) completed a treatment course with an antibacterial drug for an
infection other than ABSSSI and the drug does not have activity against bacterial pathogens that
cause ABSSSI
The patient received only 1 dose of either a single, potentially effective, short-acting (t1/2 ≤12
hours) antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of the ABSSSI
under study before enrollment. (Note: 1 dose of a regimen is defined as the standard therapy for
ABSSSI at the study site.)
Patients who received 1 dose of either a single, potentially effective, short-acting antimicrobial drug
or regimen for treatment of the ABSSSI under study in the 14 days before study entry will be
limited to no more than 25% of total randomized patients.
9. Anticipated to require either an amputation or multiple debridement procedures.
10. Anticipated that the ABSSSI under treatment will require more than 28 doses of antibiotic therapy.
11. Severely compromised immune systems, eg:
Known absolute neutropenia (absolute neutrophil count <500 cells/µL)
Known human immunodeficiency virus infection with a CD4 count <350 cells/µL within the last 4
months
Cancer chemotherapy or radiation in the last 3 months
During the period starting from 14 days before study drug administration through the Follow-up
Visit, the anticipated cumulative use of systemic corticosteroids is >10 days and the anticipated
corticosteroid dose is equivalent to >15 mg prednisone per day
12. Known history of Child-Pugh Class B or C liver disease
13. Alanine aminotransferase >3× ULN.
14. Patients with end-stage renal disease on hemodialysis or peritoneal dialysis or CrCl of <15 mL/min
using the Cockcroft-Gault formula
15. Patients with ongoing treatment for seizures or untreated history of seizures.
16. Life expectancy of <3 months.
17. Immediate life-threatening disease.
18. Any underlying disease (eg, severe cardiac disease, malignancy, or psychiatric disorder) that, in the
opinion of the investigator, may interfere with the patient’s ability to participate in the study.
19. Prior treatment with delafloxacin within the last year.
20. Receipt of an investigational drug within 30 days of randomization.
21. Prior randomization in this study.
22. Body weight >200 kg.
23. Would require a total infusion time for vancomycin of >3 hours per dose (eg, >3000 mg per 3-hour
dose).
24. History or physical examination finding of peripheral neuropathy.
Laboratory tests with exclusionary results judged by the investigator as not compatible with the patient's
clinical status may be repeated for eligibility purposes once.
vancomycin, or vancomycin derivatives according to the judgment of the investigator.
2. Women who are pregnant or lactating.
3. Any chronic or underlying skin condition at the site of infection that may complicate the assessment
of response (eg, atopic dermatitis or eczema). Any other skin condition that, in the opinion of the
investigator, would interfere with objective measurement of the ABSSSI under treatment.
4. Infection associated with a prosthetic joint or the removal of a prosthetic joint, or infection involving
other prosthetic materials or foreign bodies (eg, catheter tunnels) unless that other prosthetic material
will be removed within 24 hours after starting study drug.
5. Infection associated with any of the following:
Human or animal bite (insect bites are not considered animal bites)
Osteomyelitis
Decubitus ulcer
Diabetic foot ulcer
Septic arthritis
Mediastinitis
Sternal wound
Necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis
Myositis
Tendinitis
Endocarditis
Toxic shock syndrome
Sustained shock (blood pressure <90 mm Hg for >2 hours despite adequate fluid resuscitation, with
evidence of hypoperfusion or use of sympathomimetic agents to maintain blood pressure)
Gangrene or gas gangrene
Burns covering 10% of body surface area
Severely impaired arterial blood supply to an extremity with an ABSSSI (a patient with a palpable
distal pulse or an audible distal pulse by Doppler may be enrolled)
Current evidence of deep vein thrombosis or superficial thrombophlebitis
Any infection types with poor circulatory status in the opinion of the investigator
6. Minor abscesses, unless present with 1 of the 4 acceptable types of ABSSSIs noted in inclusion
criteria.
7. Any infection expected to require other systemic antibacterial agents in addition to study drug.
8. Receipt of systemic antibiotic therapy in the 14 days before enrollment unless one of the following is
documented:
The patient received at least 48 hours of antibiotic therapy for ABSSSI AND the clinic notes or
photographs document the clinical progression of ABSSSI (ie, not by patient history alone)
The patient recently (within 14 days) completed a treatment course with an antibacterial drug for an
infection other than ABSSSI and the drug does not have activity against bacterial pathogens that
cause ABSSSI
The patient received only 1 dose of either a single, potentially effective, short-acting (t1/2 ≤12
hours) antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of the ABSSSI
under study before enrollment. (Note: 1 dose of a regimen is defined as the standard therapy for
ABSSSI at the study site.)
Patients who received 1 dose of either a single, potentially effective, short-acting antimicrobial drug
or regimen for treatment of the ABSSSI under study in the 14 days before study entry will be
limited to no more than 25% of total randomized patients.
9. Anticipated to require either an amputation or multiple debridement procedures.
10. Anticipated that the ABSSSI under treatment will require more than 28 doses of antibiotic therapy.
11. Severely compromised immune systems, eg:
Known absolute neutropenia (absolute neutrophil count <500 cells/µL)
Known human immunodeficiency virus infection with a CD4 count <350 cells/µL within the last 4
months
Cancer chemotherapy or radiation in the last 3 months
During the period starting from 14 days before study drug administration through the Follow-up
Visit, the anticipated cumulative use of systemic corticosteroids is >10 days and the anticipated
corticosteroid dose is equivalent to >15 mg prednisone per day
12. Known history of Child-Pugh Class B or C liver disease
13. Alanine aminotransferase >3× ULN.
14. Patients with end-stage renal disease on hemodialysis or peritoneal dialysis or CrCl of <15 mL/min
using the Cockcroft-Gault formula
15. Patients with ongoing treatment for seizures or untreated history of seizures.
16. Life expectancy of <3 months.
17. Immediate life-threatening disease.
18. Any underlying disease (eg, severe cardiac disease, malignancy, or psychiatric disorder) that, in the
opinion of the investigator, may interfere with the patient’s ability to participate in the study.
19. Prior treatment with delafloxacin within the last year.
20. Receipt of an investigational drug within 30 days of randomization.
21. Prior randomization in this study.
22. Body weight >200 kg.
23. Would require a total infusion time for vancomycin of >3 hours per dose (eg, >3000 mg per 3-hour
dose).
24. History or physical examination finding of peripheral neuropathy.
Laboratory tests with exclusionary results judged by the investigator as not compatible with the patient's
clinical status may be repeated for eligibility purposes once.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
660 participants
