Complicated skin and skin structure infections are predominantly caused by the following Gram-positive pathogens: Staphylococcus aureus, including methicillin-resistant strains, beta hemolytic streptococci (most commonly S. pyogenes and S. agalactiae), enterococcus spp., and viridans group streptococci. MedDRA version: 7.0 Level: HLT Classification code 10040786
Conditions
Interventions
Product Name: Iclaprim
Product Code: AR-100 (base) AR-100.001 (mesilate)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: iclaprim
Current Sponsor code: 192314-93-5
Oth
Sponsors
Arpida AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Hospitalized with clinical evidence of at least 1 of the following: a.Infected ulcers, b.First or second degree burns of less than 20% of body surface area with concomitant signs of cellulites (excluding third degree burns and burns >20% of body surface area), c.Major abscess, d.Deep or extensive cellulites, and/or e.Wound infections. 2.Presence of purulent or seropurulent drainage or at least 3 of the following signs and symptoms: a.Drainage and/or discharge, b.Erythema (extending at least 1 cm beyond a wound edge), c.Swelling and/or induration, d.Heat and/or localized warmth, and/or e.Pain and/or tenderness to palpation. 3.At least 1 of the following conditions considered to be pathogen-related: -Fever (temperature >38°C/100.4°F orally, rectally, or tympanically), -Elevated total peripheral white blood cells (WBCs) >10,000/mm3, or ->15% immature neutrophils (bands), regardless of total peripheral WBC count. 4.Accessible infection site for culture; 5.At least 18 years of age. 6.Written informed consent to participate in the study before any study-specific screening procedures are performed. If any patient is unable to give consent, it may be obtained from the patient’s next of kin or legally acceptable representative in accordance with local laws and legislation. 7.If female, must either: 7a. be post-menopausal for at least 1 year, 7b. have had a hysterectomy of tubal ligation 7c. if of childbearing potential have maintained her normal menstrual pattern for the 3 months prior to study entry, and have taken hormonal contraceptives for at least 1 month prior to study entry; 7d. if of childbearing potential agree to use spermicide and barrier methods; 7e. if of childbearing potential be using another medically acceptable method of contraception and agrees to continue with the same method during the study;has a negative serum pregnancy test (serum beta-human chorionic gonadotropin [hCG] result immediately prior to enrollment. If obtaining the serum pregnancy result would cause a delay in treatment, the patient can be entered on the basis of a negative urine pregnancy test result. The urine pregnancy test must be sensitive to at least 50 mU/mL of beta-hCG, pending results of serum test. The patient must end study medication therapy if the serum pregnancy test is positive Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Complicated skin and skin structure infections of the following categories: a.Severely impaired arterial blood supply such as that amputation of the infected anatomical site is likely, b.Infected diabetic foot ulcers or decubitus ulcers, c.Infected human or animal bites, d.Necrotizing fasciitis or gangrene, e.Uncomplicated skin or skin structure infection, f.Self-limiting infections such as isolated folliculitis or other infection that has a high surgical incision cure rate or furunculosis or carbunculosis that is not associated with a cellulitis at least 1 cm in radius, g.Skin and/or skin structure infection that can be treated by surgery alone, h.Infections associated with a prosthetic device, and i.Suspected or confirmed osteomyelitis. 2.Known or suspected concurrent infection or conditions requiring systemic anti-infective treatment, prophylaxis, or suppression therapy (excluding ongoing suppression therapy for herpes simplex virus); 3.Known or suspected human immunodeficiency virus (HIV)-infected patients with cluster of differentiation (CD4) count 24 hours’ coverage of Gram positive pathogens by any systemic antibiotic or any topical antibiotic at the infection site within the last 7 days, unless there is evidence of treatment failure or documented resistance of Gram-positive pathogens to the previous antibiotic therapy; 7.Complicated skin and skin structure infections suspected or documented as being due exclusively to Gram-negative or anaerobic organisms based on epidemiological grounds or on direct examination of a specimen with Gram’s stain (mixed complicated skin and skin structure infections in which both Gram-positive and Gram-negative pathogens are isolated may be enrolled if the clinician suspects that the predominant causative pathogen is a Gram-positive organism); 8.Infections due to a Gram-positive organism known to be resistant to linezolid and/or mixed complicated skin and skin structure infections in which the Gram-negative organisms are known to be resistant to aztreonam; 9.Complicated skin and skin structure infections known or suspected to be a fungal, parasitic or viral infection; 10.Concomitant morbidity of such severity that the patient is likely to die or present with serious medical conditions within 30 days of study entry; 11.Known or suspected local or systemic hypersensitivity to trimethoprim, linezolid, or related compounds; 12.Morbid obesity defined as a body mass index >40 or weight >150 kg; 13.Pregnant or lactating female; 14.Severe renal impairment with CrCL 5 times the upper limit of normal and/or bilirubin >1.5 times the upper limit of normal; 16.Requirements for steroids >10 mg/day, prednisolone or equivalent, or received steroids >10 mg/day prednisolone or equivalent in the past 3 days; 17.Cardiovascular conditions and treatments: a.Patients known to have congenital or sporadic syndromes of QTc prolongation, b.Type IA or III anti-arrhythmic drugs, c.Non-sustained ventricular tachycardia defined as =10 consecutive ventricular beats at a rate of >120 beats per minute with a duration of <30 seconds, d.Bradycardia (<50 beats per minute), and e.QT/QTc interval outside
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the clinical cure rates of iclaprim and linezolid at the test of cure visit (7 to 14 days after the end of treatment).;Secondary Objective: The secondary objectives of this study are to compare iclaprim with linezolid regarding: 1.Clinical efficacy at the end of study medication treatment; 2.Time to resolution of systemic and local signs and symptoms of complicated skin and skin structure infections; 3.Clinical outcome in the microbiology evaluable population; 4.Bacteriologic outcome in the microbiology evaluable population; 5.Bacteriologic eradication rates of baseline pathogens; 6.Clinical outcome in the modified intent-to-treat population; 7.Bacteriologic outcome in the modified intent-to-treat population; 8.Baseline in vitro susceptibility of isolated pathogens in the microbiology evaluable population; 9.Safety and tolerability of iclaprim treatment; 10.To obtain population pharmacokinetic data for patients who received iclaprim.;Primary end point(s): The primary efficacy endpoint is clinical cure rate based on all patients in the Per Protocol and Intent-to-Treat populations at the test of cure visit.Safety endpoints are changes from baseline in adverse events, serious adverse events, hematology, clinical chemistry, and urine test results, vital signs, physical examinations and EGG tests. | — |
Countries
Latvia
Outcome results
None listed