E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS |
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E.1.1.1 | Medical condition in easily understood language |
Bacterial infection of the skin. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052891 |
E.1.2 | Term | Skin bacterial infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the clinical efficacy of delafloxacin compared with vancomycin + aztreonam in patients with ABSSSIs at the Follow-up Visit (Day 14 +/- 1). |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the clinical efficacy of delafloxacin compared with vancomycin + aztreonam by assessing the investigator-assessed response of signs and symptoms of infection at the Follow-up Visit
•To evaluate the clinical efficacy of delafloxacin compared with vancomycin + aztreonam by assessing the investigator-assessed response of signs and symptoms of infection at the Late Follow-up Visit
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult (≥18 years of age) men or women.
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 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 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 multiplied by the longest perpendicular width using a disposable ruler
• Burn infection: An infection characterized by purulent drainage, redness, edema, and/or induration 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 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 understand the informed consent form (ICF).
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E.4 | Principal 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
6. Minor abscesses, unless present with 1 of the 4 acceptable types of ABSSSIs noted in Section 3.2.1.
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 7 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 (half-life [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 at each site.
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 (HIV) infection with a CD4 count <350 cells/µL within the last 4 months
• Cancer chemotherapy or radiation in the last 3 months
• Expected treatment with >15 mg per day systemic prednisone or equivalent for more than 10 days within the period starting 14 days before study drug administration or anticipated through Follow up
12. Known history of Child Pugh Class B or C liver disease (Table 6 2).
13. Alanine aminotransferase >3× ULN.
14. Patients with end stage renal disease on hemodialysis or peritoneal dialysis or creatinine clearance of ≤30 mL/minute using the Cockcroft Gault formula (Section 6.3).
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 >140 kg.
23. Would require a total infusion time for vancomycin of >2 hours per dose (eg, >2500 mg per 2 hour dose).
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-assessed response of signs and symptoms of infection at the Follow-up Visit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 14 +/- 1 after initiation of treatment
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E.5.2 | Secondary end point(s) |
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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
48 to 72 hours after initiation of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
Latvia |
Lithuania |
Israel |
Romania |
Russian Federation |
Ukraine |
Bulgaria |
Croatia |
Spain |
Hungary |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patients will receive a follow up telephone call 30 days after their last dose of study drug to assess patient status and to check for AEs and posttreatment medications. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 15 |
E.8.9.2 | In all countries concerned by the trial days | 0 |