A Phase III, Prospective, Randomized, Double Blind, Double Dummy, Active Controlled, Comparative, Parallel Group, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Tedizolid Tablets 200 mg Versus Linezolid Tablets 600 mg in Adult Patients for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 242
- 试验地点
- 19
- 主要终点
- Early clinical response assessed at 48 to 72 hours after initiation of treatment, whereby a patient could either be classified as either:
研究概览
简要总结
This trial is a phase III, prospective, randomized, double blind, double dummy, active controlled, comparative, parallel group, multicenter clinical study to evaluate the efficacy, safety and tolerability of Tedizolid Tablets 200 mg versus Linezolid Tablets 600 mg in adult patients for the treatment of acute bacterial skin and skin structure infections (ABSSSI).
Patients who are willing and able to participate in the study will sign and date the Informed Consent Form on the day of screening / baseline visit (Visit 1). During this screening period, patients who are willing to give consent will be evaluated for all the eligibility criteria. Eligible patients aged between 18 to 65 years (both inclusive) with qualifying acute bacterial skin & skin structure infections (ABSSSI) confirmed to be due to gram positive pathogens will be considered for the study.
After confirming the inclusion/exclusion criteria the subject will be randomized and provided with study drug at randomization visit. Subjects will be provided with a diary at randomization visit, which need to be brought along with in each subsequent visit till the last visit. Follow up visits will be done on Day 1, Day 2, Day 3, Day 7, Day 11+2 (End of treatment visit), Post treatment evaluation (PTE) visit (7 to 14 days after the EOT visit / Day 18 to Day 25) and End of the study (EOS) visit or Late follow up (LFU) visit (18 to 25 days after the EOT visit / Day 29 to 36) to assess efficacy, safety and tolerability.
Patients will be assigned to either of the two arms i.e., Arm A or Arm B consisting of Tedizolid Tablets 200 mg (Patients will be advised to take one Tablet of Tedizolid Tablets 200 mg plus one Tablet of Placebo followed 12 hours later by one Tablet of Placebo from day 1 to day 6, and 3 Tablets of Placebo from day 7 to day 10) or Linezolid Tablets 600 mg (Patients will be advised to take one Tablet of Linezolid Tablets 600 mg plus one Tablet of Placebo followed 12 hours later by one Tablet of Linezolid Tablets 600 mg from day 1 to day 10).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients aged between 18 to 65 years (both inclusive).
- •Patients with acute bacterial skin and skin structure infections (ABSSSI) meeting at least one of the clinical syndromes listed below and requiring oral antibacterial therapy.
- •Local symptoms must have started within 7 days before the screening visit.
- •Cellulitis/erysipelas Wound infection Major cutaneous abscess
- •Patients with suspected or documented Gram-positive infection from baseline Gram stain or culture.
- •Patient with ability to understand and provide written, signed and dated informed consent form, which must have been obtained prior to any assessment performed.
- •Patients willing to comply with the protocol requirements.
排除标准
- •Patients with uncomplicated skin and skin structure infections such as furuncles, minor abscesses (area of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, and minor wound infections (e.g., stitch abscesses).
- •Patients with infections associated with, or in close proximity to, a prosthetic device.
- •Patients with severe sepsis or septic shock.
- •Patients with known bacteremia at time of screening.
- •Patients with acute bacterial skin and skin structure infection (ABSSSI) due to or associated with any of the following: Suspected or documented Gram-negative pathogens in patients that require an antibiotic with specific Gram-negative coverage.
- •Diabetic foot infections, gangrene, or perianal abscess Concomitant infection at another site not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis) Infected burns Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous) Any evolving necrotizing process (i.e., necrotizing fasciitis) Infected human or animal bites.
- •However, arthropod (e.g., insects, spiders, ‘bugs’) bites are allowed only if subject actually witnessed the arthropod bite through the skin in the area of the ABSSSI; these are not considered animal bites in this study Infections at vascular catheter sites or involving thrombophlebitis Incision surgical site infection with any of the following characteristics: Follows clean-contaminated surgery (urgent or emergency case that is otherwise clean, elective opening of respiratory, gastrointestinal, biliary, or genitourinary tract with minimal spillage [e.g., appendectomy] not encountering infected urine or bile; minor technique break) Follows contaminated surgery (non-purulent inflammation; gross spillage from gastrointestinal tract; entry into biliary or genitourinary tract in the presence of infected bile or urine; major break in technique; chronic open wounds to be grafted or covered) Follows dirty surgery (purulent inflammation [e.g., abscess]; preoperative perforation of respiratory, gastrointestinal, biliary, or genitourinary tract) Extends into the fascia or muscle layers, organs, or spaces
- •Patients with use of antibiotics as follows: Systemic antibiotic with activity against Gram-positive cocci for the treatment of any infection within 24 hours before the first dose of study drug Patients who failed prior therapy for the primary infection site are also excluded from enrollment Topical antibiotic on the primary lesion within 24 hours before the first dose of study drug except for antibiotic/antiseptic-coated dressing applied to the clean post-surgical wound
- •Patients with administration of Linezolid within 30 days before the first infusion of the study drug.
- •Patients with recent history of opportunistic infections where the underlying cause of these infections is still active (e.g., leukemia, transplant, acquired immunodeficiency syndrome [AIDS]).
- •Patients receiving chronic systemic immunosuppressive therapy such as Prednisone doses ≥20 mg per day for ≥3 of the last 12 months or therapies that in the Investigator’s judgement could predispose to opportunistic infections.
- •Patients with chronic (daily for the previous 30 days) use of antipyretic medication (e.g., Acetaminophen, Paracetamol, non-steroidal anti-inflammatory drugs).
- •Low-dose Aspirin (≤200 mg per day) for cardiovascular prophylaxis is allowed.
- •Patients receiving treatment for active tuberculosis.
- •Patients with current or anticipated neutropenia with absolute neutrophil count <1000 cells/mm
- •Patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
- •Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the UNL and/or Total bilirubin ≥ 2 mg/dL) at screening.
- •Patients with the Body Mass Index (BMI) ≥ 40.0 kg/m2 at screening.
- •Patients with history of significant or life-threatening condition or organ or system condition or disease (e.g., endocarditis, meningitis, unstable CNS conditions, acidosis or history of lactic acidosis) that would confound or interfere with the assessment of the ABSSSI.
- •Patients with any abnormality on 12-lead ECG at screening that in the opinion of the investigator is clinically significant and is judged as potential risk for patient’s participation in the study.
- •Patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or thyrotoxicosis, the use of the following medications within 2 days before the first infusion of study drug or planned use through the end of treatment (EOT) visit: Systemic use of directly and indirectly acting sympathomimetic agents (e.g., Pseudoephedrine, Phenylpropanolamine), vasopressive agents (e.g., Epinephrine, Norepinephrine), or dopaminergic agents (e.g., Dopamine, Dobutamine).
- •Use of a small amount of a vasoconstrictor (e.g., Lidocaine containing Epinephrine) during a minor surgical procedure under local anesthesia (e.g., incision and drainage) is allowed.
- •Patients with the use of the following medications within 14 days before the first dose of study drug or planned use through the EOT visit: Monoamine oxidase A and B inhibitors (e.g., Phenelzine, Isocarboxazid) Serotonergic agents including antidepressants such as selective serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin 5- hydroxytryptamine receptor agonists (triptans%2.
结局指标
主要结局
Early clinical response assessed at 48 to 72 hours after initiation of treatment, whereby a patient could either be classified as either:
时间窗: At Visit 4 / Day 3.
a) having clinical response (responder)
时间窗: At Visit 4 / Day 3.
b) having clinical failure (non-responder)
时间窗: At Visit 4 / Day 3.
次要结局
- Investigator’s assessment of clinical response at 48–72-hour visit.(At Visit 4 / Day 3.)
- Investigator’s assessment of clinical response at Day 7 visit.(At Visit 5 / Day 7.)
- Programmatic objective clinical response at EOT (Day 11) visit.(At Visit 6 / Day 11.)
- Investigator’s assessment of clinical response at EOT and post-therapy evaluation (PTE) visits.(At Visit 6 / Day 11 and)
- Investigator’s assessment of clinical response at late follow-up visit.(At Visit 8 / Day 29 to Day 36.)
- Lesion size.(At Visit 1 or Day -1,)
- Microbiology of the infection(At Visit 1 or Day -1,)
- Patient’s subjective assessment of pain.(At Visit 1 or Day -1,)
- Adverse events and/or serious adverse events reported during the study.(Throughout the study.)
研究者
Dr Rajasekhara Reddy Tamma
Clinwave Research Pvt. Ltd.