A Phase III Randomized, Active-comparator-Controlled Clinical Trial to Study the Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator, in Subjects From Birth to Less Than 12 Years of Age With 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
- 100
- 试验地点
- 58
- 主要终点
- Number of Participants With Hematopoietic Cytopenias
研究概览
简要总结
This study will evaluate the safety, tolerability, and efficacy of tedizolid phosphate (MK-1986) compared with comparator antibacterial agent in participants from birth to less than 12 years of age with acute bacterial skin and skin structure infections (ABSSSI).
详细描述
Participants will be randomized (3:1) to receive tedizolid phosphate at a weight-based dose ≤200 mg/day, intravenous (IV) and/or oral suspension for 6 to 10 days, or comparator IV and/or oral per local standard of care for 10 to 14 days. The switch from IV to oral administration can be made at any time based on 1) no worsening of the primary skin lesion, 2) last temperature <37.7 °C, and 3) primary acute bacterial skin and skin structure infection (ABSSSI) site has not worsened and at least 1 site has improved from Baseline. The potential 4-day treatment extension will be based on clinical need as judged by the investigator, considering the following criteria: 1) ≥40% reduction in primary lesion size, 2) reduction in pain, and 3) no new signs and symptoms and no complications attributable to ABSSSI compared with Baseline.
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
- Single (Outcomes Assessor)
盲法说明
Single blinded
入排标准
- 年龄范围
- 1 Day 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a parent/legally acceptable representative who is able to give documented informed consent
- •Has acute bacterial skin and skin structure infections (ABSSSI), defined as ≥1 of the following: 1) cellulitis/erysipelas, 2) major cutaneous abscess, or 3) wound infection
- •Local symptoms of ABSSSI that started within 14 days before study start
- •Suspected or documented Gram-positive bacterial infection
排除标准
- •Uncomplicated skin and skin structure infection
- •ABSSSI due to or associated with disallowed etiology per protocol
- •Received antibacterial therapy for treatment of the current episode of ABSSSI except 1) <48 hours of antibacterial therapy with a short-acting antibacterial drug, or 2) response is considered to be failure (no improvement in signs and symptoms) after at least 48 hours of therapy
- •Known bacteremia, severe sepsis, or septic shock
- •Significant or life-threatening condition, disease, or organ system condition
- •Recent history of opportunistic infections where the underlying cause of the infection is still active, or is suspected to be at risk of opportunistic infection with unusual pathogens
- •Received or is receiving treatment for active tuberculosis within 1 month of study start
- •Known or suspected severe neutropenia
- •Human immunodeficiency virus (HIV) positive and has Cluster of Differentiation (CD) 4 cell count <15% (HIV testing is not required for eligibility)
- •Renal impairment that requires renal filtration
- •Severe hepatic impairment
- •Cardiac or electrocardiogram (ECG) finding that would limit participation in the study
- •Received an investigational medicinal product (not approved) within 30 days before study start
- •Investigational device present or removed within 30 days before study start
- •Previously treated with tedizolid phosphate
- •Contraindication, including hypersensitivity to tedizolid phosphate, other oxazolidinones, or any component in the formulation
- •Contraindication, including hypersensitivity to all available comparator drugs
- •Wound infection and history of hypersensitivity to aztreonam adjunctive therapy or metronidazole adjunctive therapy, if adjunctive therapy is required
- •Needs oral administration of methotrexate, topotecan, irinotecan, or rosuvastatin, during administration of oral study drug (administration during the follow-up period, ie, after the end of treatment (EOT) visit, is allowed, as is administration during treatment with IV drug)
- •Female who is pregnant or nursing or is of childbearing potential and not abstinent; or male who is not abstinent
- •Use of monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors, or serotonin 5-hydroxytryptamine receptor agonists (triptans)
- •Identified as having used illicit drugs (urine drug screening not required for entry)
研究组 & 干预措施
Cohort 1: Tedizolid phosphate 6 to <12 Years
Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.
干预措施: Tedizolid phosphate (Drug)
Cohort 1: Comparator 6 to <12 Years
Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.
干预措施: Comparator (Drug)
Cohort 2: Tedizolid phosphate 2 to <6 Years
Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.
干预措施: Tedizolid phosphate (Drug)
Cohort 2: Comparator 2 to <6 Years
Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.
干预措施: Comparator (Drug)
Cohort 3: Tedizolid phosphate 28 Days to <2 Years
Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.
干预措施: Tedizolid phosphate (Drug)
Cohort 3: Comparator 28 Days to <2 Years
Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.
干预措施: Comparator (Drug)
Cohort 4: Tedizolid phosphate Birth to <28 Days Term and Preterm Neonates
Participants will receive tedizolid phosphate ≤200 mg daily dose, IV and/or oral suspension for 6 to 10 days. Exact mg/kg dose is to be determined based on results of another study (NCT03217565) covering the age range.
干预措施: Tedizolid phosphate (Drug)
Cohort 4: Comparator Birth to <28 Days Term and Preterm Neonates
Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days.
干预措施: Comparator (Drug)
结局指标
主要结局
Number of Participants With Hematopoietic Cytopenias
时间窗: Up to approximately 35 days
Hematopoietic cytopenia is a condition where there is a lower-than-normal amount of one or multiple kinds of blood cells. A standardized Medical Dictionary for Regulatory Activities (MedDRA) query for hematopoietic cytopenia was conducted. The number of participants with a hematopoietic cytopenia were reported.
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 35 days
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who experienced an AE were reported.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately day 15
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who experienced an AE were reported. The number of participants who discontinued study treatment due to an AE were reported.
次要结局
- Percentage of Participants With Clinical Response (CR) Per Investigator Assessment(Up to approximately 25 days)
- Percentage of Clinically Evaluable (CE) Participants With CR Per Investigator Assessment(Up to approximately 25 days)