A Phase 3, Randomized, Multicenter, Double-Blind Study to Evaluate the Efficacy and Safety of Plazomicin Compared With Meropenem Followed by Optional Oral Therapy for the Treatment of Complicated Urinary Tract Infection (cUTI), Including Acute Pyelonephritis (AP), in Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 609
- 主要终点
- Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
研究概览
简要总结
This was a randomized, multicenter, multinational, double-blind study comparing the efficacy and safety of plazomicin compared with meropenem followed by optional oral (PO) therapy in the treatment of cUTI, including AP, in adults.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a pretreatment baseline urine culture obtained within 36 hours before the start of administration of the first dose of study drug
- •Clinical signs and/or symptoms of acute pyelonephritis or complicated urinary tract infection
- •Normal renal function or moderate renal impairment
排除标准
- •Confirmed fungal urinary tract infection at the time of randomization
- •Known urinary tract infection or colonization with Gram-positive pathogens
- •Current cUTI or AP is known to be caused by a pathogen resistant to meropenem
- •Female participants of childbearing potential if they are known to be pregnant or have a positive pregnancy test at screening, breastfeeding, or unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication
- •Any rapidly progressing disease or immediately life-threatening illness
- •Documented presence of immunodeficiency or an immunocompromised condition
- •Documented or known history of otologic surgery or disease including use of hearing aid, head injury leading to otologic damage, Ménière's disease, tumor of the head, neck, or auditory system, perilymphatic fistula, or autoimmune disease of the inner ear, or family history of hearing loss (excluding age-related hearing loss [onset after age of 65 years])
研究组 & 干预措施
Plazomicin
Patients received 15 milligrams per kilogram (mg/kg) plazomicin as an intravenous (IV) infusion once daily followed by matching placebo infusions 8 and 16 hours later. After a minimum of 4 days of IV plazomicin, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).
干预措施: plazomicin (Drug)
Plazomicin
Patients received 15 milligrams per kilogram (mg/kg) plazomicin as an intravenous (IV) infusion once daily followed by matching placebo infusions 8 and 16 hours later. After a minimum of 4 days of IV plazomicin, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).
干预措施: levofloxacin (oral) (Drug)
Meropenem
Patients received 1.0 g meropenem as an IV infusion every 8 hours (q8h). After a minimum of 4 days of IV meropenem, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).
干预措施: meropenem (Drug)
Meropenem
Patients received 1.0 g meropenem as an IV infusion every 8 hours (q8h). After a minimum of 4 days of IV meropenem, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).
干预措施: levofloxacin (oral) (Drug)
结局指标
主要结局
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
时间窗: Day 5
Microbiological eradication was defined as a urine culture that showed the pathogen found at baseline at ≥10\^5 colony forming units per milliliter (CFU/mL) was reduced to \<10\^4 CFU/mL. Clinical Cure at Day 5: marked improvement evidenced by complete resolution or return to premorbid levels or reduction in severity of all core baseline symptoms with worsening of none, and no new symptoms developed. Failure: Lack of improvement in core baseline symptoms of cUTI or development of new core symptoms of cUTI; adverse event (AE) requiring the discontinuation of study drug and the patient required alternative non-study antibiotic therapy for the current cUTI. Indeterminate: Insufficient data are available to allow an evaluation of clinical outcome for any reason.
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)
时间窗: Day 17 TOC Visit
Microbiological eradication was defined as a urine culture that showed the pathogen found at baseline at ≥10\^5 CFU/mL was reduced to \<10\^4 CFU/mL. Clinical Cure at TOC Visit: the complete resolution or return to premorbid levels of core symptoms of cUTI and no new symptoms develop, and no use of non-study antibiotic therapy for the current cUTI. Failure: Persistence of one or more core symptom of infection or reappearance of or development of new core symptoms that require alternative non-study antibiotic therapy for the current cUTI. Indeterminate: Insufficient data are available to allow an evaluation of clinical outcome for any reason.
次要结局
- Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)(Up to Day 32)
- Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin)(Day 3)
- Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5(Day 5)
- Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)(Day 3)
- Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)(Day 3)
- Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC(Day 17 TOC Visit)