| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Caused by Staphylococcus
aureus |
| Oстри бактериални инфекции на кожата и кожните структури (ОБИККС), причинени от Стафилококус ауреус |
|
| E.1.1.1 | Medical condition in easily understood language |
| Acute Bacterial Skin and Skin Structure Infections caused by the bacterial agent Staphylococcus aureus |
| Oстри бактериални инфекции на кожата и кожните структури , причинени от бактериалния причинител Стафилококус ауреус |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10040786 |
| E.1.2 | Term | Skin structures and soft tissue infections |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
| The Primary objective of this study is to assess the efficacy of PMX-30063 therapy in patients treated for acute bacterial skin and skin-structure infection. The primary measure of efficacy will be bacteriologic eradication at end of treatment (day 7/8) of S. aureus (either MSSA or MRSA) in subjects with ABSSSI and having S. aureus isolated from an appropriate infection site prior to randomization. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess early clinical response at 48-72 hours using objective data including precise dimensions of infection site, changes in temperature and leukocytosis, and photographic evidence of inflammation (purulence, erythema and induration).
- To further evaluate the safety of PMX-30063 in the enrolled patients and the pharmacokinetic factors (peak and trough levels) that may control it.
- To more exactly describe the nature and course of the sensory symptoms that appear to characterize the toxic side effects.
- To examine the relationship between a known indicator of inflammation, C-Reactive Protein (CRP), and the resolution of infection. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provide written informed consent
2. Be ≥ 18 years of age and <85 years of age
3. Have a diagnosis of ABSSSI in which S. aureus is clinically suspected to be the likely pathogen
4. Clinical manifestation of subjects’ ABSSSI must include the presence of purulent material suitable for microbiologic culture, Gram stain examination and PCR assay.
5. The ABSSSI must be 75 cm2 or greater in size in order for the subject to be eligible for this study. This includes the primary lesion and surrounding erythema, swelling or induration.
6. Have not received more than 24 hours of active treatment with another systemic antibiotic for the current ABSSSI within 72 hours prior to randomization, unless resistance has been established by showing that there is:
a. Clinical evidence of treatment failure following at least 48 hours of prior systemic antimicrobial therapy; OR
b. Microbiological evidence of failure including EITHER a Gram stain which reveals white blood cells and Gram-positive cocci in clusters obtained at least 48 hours after the first dose of a prior systemic antibacterial
OR
prior isolation of a S. aureus organism which is resistant in vitro to the prior systemic antibacterial therapy at any time after initiation of such antibiotic therapy.
c. Positive PCR assay (Xpert® MRSA/SA SSTI) for S. aureus.
Note: not all sites will have PCR technology available. When sites do not have Xpert®MRSA/SA SSTI (Cepheid, Sunnyvale, CA) technology, inclusion criteria “c” is not applicable.
7. Requires parenteral therapy for the infection, which is expected to continue for at least 7 days
8. Presents with at least TWO of the following local symptoms of infection:
a. Erythema
b. Fluctuance
c. Heat/Localized Warmth
d. Pain/tenderness to palpation
e. Swelling/induration
f. Lymph node enlargement and/or tenderness in the area of drainage from the infected site |
|
| E.4 | Principal exclusion criteria |
1. Female patients who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study. Woman of child bearing potential (WOCBP)* who are not using an acceptable method of birth control (i.e., intrauterine device, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with
contraceptive cream, jelly or foam). WOCBP with a positive urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
*WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12
consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL).
2. History of peripheral neuropathy of any form or etiology
3. Anticipated need for prolonged antibiotic therapy (i.e., >8 days)
4. ABSSSI known or suspected to be caused exclusively by Gram negative pathogens or anaerobes (both Gram positive or Gram negative)
5. ABSSSI known or suspected to be caused by non-bacterial infections
6. Known or suspected osteomyelitis or septic arthritis
7. Super-infected eczema or other chronic medical conditions (e.g., atopic dermatitis, hidradentitis suppurativa) characterized by prominent signs of inflammation for an extended period even after successful bacterial eradication. (Subjects with an ABSSSI that involves an anatomic location in which there is no evidence of a chronic skin condition are eligible for enrollment.)
8. Diabetic foot infection: defined as a subacute or chronic infection (> 4 weeks) below the ankle in a patient with diabetic neuropathy
9. Infected burns
10. Chronic skin ulcer present for over 2 months
11. Peri-rectal abscess or infected pilonidal cyst
12. Infected decubitus ulcer
13. Infection associated with severe peripheral vascular insufficiency: defined as patients with prior vascular surgery of the lower extremities or the presence of distal gangrene.
14. Infection resulting from human or animal bite (infection from insect bite is eligible)
15. Suspected necrotizing fasciitis
16. Unable or unwilling to adhere to the study-specified procedures and restrictions
17. Infections related to the presence of prosthetic materials that will not be removed such as permanent intra-cardiac devices or joint replacement prostheses
18. Moderately or severely impaired renal function with known creatinine clearance <50 mL/min (based on the Cockcroft-Gault formula using ideal body weight)
19. ALT or AST >2x upper limit of normal or bilirubin >1.5 x upper limit of normal (ULN) at baseline
20. Neutropenia defined as an absolute neutrophil count < 0.5 x 103/L
21. Thrombocytopenia defined as a platelet count <50 x 103/L
22. Prolonged QTc interval >450 msec at baseline or history of prolonged QT syndrome
23. Known infection with human immunodeficiency virus (HIV) and a CD4 count < 200/mm3
24. Active hepatitis B or hepatitis C receiving treatment with interferon or other immunosuppressive therapy
25. History of penicillin hypersensitivity reaction (allergy) if subject is to receive concomitant penicillin
26. Life expectancy of less than 3 months from the time of enrollment
27. The presence of a significant risk factor for a poor clinical outcome, e.g. such as morbid obesity, which in the view of the investigator predicts that the subject will not adequately respond to a 5-7 days treatment course.
28. Use of an investigational drug or device (i.e., a drug or device without an FDA approved indication) within the previous 30 days
29. Prior exposure to PMX-30063
30. Patients with untreated hypertension (BP > 150/100 mmHg)
31. Subjects who take concomitant drugs which are metabolized by the liver through cytochrome P450 and which have a narrow therapeutic index. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is bacteriologic assessment at EOT (day 7/8). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Clinical responses, Pharmacokinetics and Safety parameters |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| baseline, during treatment, at the end of treatment and 4 weeks post treatment |
|
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 4 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 |
| Canada |
| Russian Federation |
| Ukraine |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
Print
