A Phase 3, Randomized, Double-blind, Double-dummy, Multicenter, Prospective Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Patients With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,372
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population
研究概览
简要总结
The key purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of tebipenem pivoxil hydrobromide (TBPM-PI-HBr) compared to intravenous (IV) ertapenem, in participants with complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
TBPM-PI-HBr 600 mg
TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours [q8h] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours [q24h] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance [CrCl] >30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.
干预措施: TBPM-PI-HBr (Drug)
TBPM-PI-HBr 600 mg
TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours [q8h] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours [q24h] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance [CrCl] >30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.
干预措施: Dummy Infusion (Drug)
Ertapenem 1 g
Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
干预措施: Ertapenem (Drug)
Ertapenem 1 g
Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
干预措施: Dummy tablets (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population
时间窗: From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days)
An Adverse Event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational/experimental) product, whether or not related to this product.
Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population
时间窗: Day 19 (TOC)
Overall response is participants with combined clinical cure and microbiological eradication. Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at baseline and no new symptoms, such that no further antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to \<10\^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.
次要结局
- Sustained Clinical Cure at LFU in the CE-LFU Populations(Day 25 (LFU))
- Clinical Cure at EOT in the ME-EOT Populations(Day 15 (EOT))
- Clinical Cure at TOC Days in the ME-TOC Populations(Day 19 (TOC))
- By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT)(Day 25 (LFU))
- By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations(Day 19 (TOC))
- By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations(Day 25 (LFU))
- By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population(Days 15 (EOT))
- By-Patient Microbiological Eradication at EOT in the ME-EOT Populations(Day 15 (EOT))
- By-Patient Microbiological Eradication at TOC in the ME-TOC Population(Day 15 (TOC))
- Cmax in TBPM-PI-HBr Recipients in the PK Population(Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3)
- Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population(Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3)
- Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population(Day 19 (TOC))
- Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations(Days 15 (EOT), Day 19 (TOC) and Day 25 (LFU))
- Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations(Day 15 (EOT))
- Clinical Cure at TOC in the CE-TOC Populations(Day 19 (TOC))
- Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1(Day 25 (LFU))
- Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population(Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3)
- Sustained Clinical Cure at LFU in the ME-LFU Population(Day 25 (LFU))
- By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population(Days 15 (EOT), 19 (TOC) and 25 (LFU))
- By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations(Day 15 (EOT))
- By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population(Day 19 (TOC))
- By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations(Day 25 (LFU))
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region(Day 25 (LFU))
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category(Day 19 (TOC))
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category(Day 19 (TOC))
- Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations(Day 25 (LFU))
- Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population(Day 25 (LFU))
- Rates Of Superinfection And New Infection In The Micro-ITT Population(Day 25 (LFU))
- Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population(Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3)
- Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population(Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3)