A Study of Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator in Participants From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (MK-1986-018)
- Conditions
- Acute Bacterial Skin and Skin Structure Infections
- Interventions
- Drug: Comparator
- Registration Number
- NCT03176134
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Tedizolid phosphate 6 to <12 Years Tedizolid phosphate 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. Cohort 2: Tedizolid phosphate 2 to <6 Years Tedizolid phosphate 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. Cohort 4: Comparator Birth to <28 Days Term and Preterm Neonates Comparator Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days. Cohort 1: Comparator 6 to <12 Years Comparator Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. Cohort 3: Tedizolid phosphate 28 Days to <2 Years Tedizolid phosphate 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. Cohort 2: Comparator 2 to <6 Years Comparator Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. Cohort 3: Comparator 28 Days to <2 Years Comparator Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. Cohort 4: Tedizolid phosphate Birth to <28 Days Term and Preterm Neonates Tedizolid phosphate 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Hematopoietic Cytopenias 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) 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Clinical Response (CR) Per Investigator Assessment Up to approximately 25 days CR was defined as clinical success, failure or indeterminate as per investigator assessment. Success was all of the following: resolution/near resolution of most disease-specific signs \& symptoms, absence/near resolution of regional/systemic signs of infection if present at baseline (BL) \& no new signs, symptoms, or complications, so, no further antibiotic therapy required. Failure was any of the following: requires additional antibiotic therapy, unplanned major surgical intervention required due to study drug failure, developed osteomyelitis after BL, persistent gram+ bacteremia, treatment emergent adverse event (TEAE) leading to study drug discontinuation \& required additional antibiotic therapy to treat infection or death within 28 days of first infusion. Indeterminate was no efficacy data available. Per protocol, percentage of participants with CR for Cohorts 1, 2 \& 3 \& all cohorts together were reported, \& failure \& indeterminate responses were pooled.
Percentage of Clinically Evaluable (CE) Participants With CR Per Investigator Assessment Up to approximately 25 days CR was defined as clinical success, failure or indeterminate as per investigator assessment. Success was all of the following: resolution/near resolution of most disease-specific signs \& symptoms, absence/near resolution of regional/systemic signs of infection if present at BL \& no new signs, symptoms, or complications, so, no further antibiotic therapy required. Failure was any of the following: requires additional antibiotic therapy, unplanned major surgical intervention required due to study drug failure, developed osteomyelitis after BL, persistent gram+ bacteremia, treatment emergent adverse event leading to study drug discontinuation \& required additional antibiotic therapy to treat infection or death within 28 days of first infusion. Indeterminate was no efficacy data available. Per protocol, percentage of participants with CR for Cohorts 1, 2 \& 3 and all cohorts together were reported, \& failure \& indeterminate responses were pooled.
Related Research Topics
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Trial Locations
- Locations (58)
Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 0129)
🇺🇸Chicago, Illinois, United States
Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0277)
🇧🇷Recife, Pernambuco, Brazil
UMHAT Deva Maria ( Site 0333)
🇧🇬Burgas, Bulgaria
MHAT City Clinic Sv. Georgi EOOD ( Site 0334)
🇧🇬Montana, Bulgaria
JSC Evex Hospitals. ( Site 0601)
🇬🇪Batumi, Ajaria, Georgia
JSC Evex Hospital ( Site 0602)
🇬🇪Tbilisi, Georgia
JSC Evex Hospitals ( Site 0603)
🇬🇪Tbilisi, Georgia
Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic ( Site 0600)
🇬🇪Tiblisi, Tbilisi, Georgia
Daugavpils Regional Hospital ( Site 0651)
🇱🇻Daugavpils, Latvia
Hospital of Lithuanian University of Health Sciences Kaunas ( Site 0701)
🇱🇹Kaunas, Lithuania
Children s Republican Clinical Hospital ( Site 0512)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Ankara City Hospital-Infectious Disease and Clinical Microbiology ( Site 0359)
🇹🇷Ankara, Turkey
Osmangazi UTF ( Site 0357)
🇹🇷Eskisehir, Turkey
William Beaumont Hospital ( Site 0108)
🇺🇸Royal Oak, Michigan, United States
Hospital Pequeno Principe ( Site 0276)
🇧🇷Curitiba, Parana, Brazil
St. Louis Children's Hospital ( Site 0127)
🇺🇸Saint Louis, Missouri, United States
Instituto D'Or de Pesquisa e Ensino (IDOR)-Hospital São Luiz Jabaquara ( Site 0283)
🇧🇷Sao Paulo, Brazil
Baylor College of Medicine - Texas Children's Hospital ( Site 0107)
🇺🇸Houston, Texas, United States
MHAT Sv. Nikolay Chudotvorets EOOD ( Site 0338)
🇧🇬Lom, Montana, Bulgaria
MHAT Dr. Stamen Iliev AD ( Site 0339)
🇧🇬Montana, Bulgaria
Cook Children's Medical Center ( Site 0124)
🇺🇸Fort Worth, Texas, United States
UMHATEM. N.I.Pirogov. EAD ( Site 0331)
🇧🇬Sofia, Bulgaria
Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCL-CENTRO DE ESTUDOS E PESQUISAS EM MOLES
🇧🇷Natal, Rio Grande Do Norte, Brazil
UMHAT Sv. Georgi ( Site 0332)
🇧🇬Plovdiv, Bulgaria
Klaipedos Vaiku Ligonine ( Site 0700)
🇱🇹Klaipeda, Lithuania
Rady Children's Hospital-San Diego ( Site 0118)
🇺🇸San Diego, California, United States
Children's Hospital of Richmond at VCU ( Site 0123)
🇺🇸Richmond, Virginia, United States
Children's Hospital of Michigan ( Site 0100)
🇺🇸Detroit, Michigan, United States
MBAL Medica Ruse EOOD ( Site 0336)
🇧🇬Ruse, Bulgaria
UMHAT Dr. Georgi Stranski EAD ( Site 0330)
🇧🇬Pleven, Bulgaria
UMHAT Kanev AD ( Site 0337)
🇧🇬Ruse, Bulgaria
Clinica Privada ( Site 0551)
🇬🇹Guatemala, Guatemala
Haunersches Kinderspital ( Site 0480)
🇩🇪München, Bayern, Germany
Private Practice Mario Melgar ( Site 0552)
🇬🇹Guatemala, Guatemala
Private Practice Dra. Manrique ( Site 0553)
🇬🇹Guatemala, Guatemala
Liepaja Regional Hospital ( Site 0652)
🇱🇻Liepaja, Latvia
Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0702)
🇱🇹Vilnius, Lithuania
Instituto Nacional de Pediatria ( Site 0231)
🇲🇽Mexico City, Distrito Federal, Mexico
Hospital Civil Fray Antonio Alcalde-pediatrics infectious diseases ( Site 0230)
🇲🇽Guadalajara, Jalisco, Mexico
Hospital Infantil de Mexico Federico Gomez ( Site 0227)
🇲🇽Mexico City, Distrito Federal, Mexico
Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0239)
🇲🇽Aguascalientes, Mexico
CHRISTUS - LATAM HUB CENTER OF EXCELLENCE AND INNOVATION S.C. ( Site 0241)
🇲🇽Gral Escobedo, Nuevo Leon, Mexico
Wojewodzki Szpital Obserwacyjno Zakazny ( Site 0429)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 0427)
🇵🇱Lodz, Lodzkie, Poland
SZPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0431)
🇵🇱Lomianki, Mazowieckie, Poland
City Childrens Clinical Emergency Hospital ( Site 0507)
🇷🇺Novosibirsk, Novosibirskaya Oblast, Russian Federation
Smolensk Regional Clinical Hospital ( Site 0511)
🇷🇺Smolensk, Smolenskaya Oblast, Russian Federation
Setshaba Research Centre ( Site 0378)
🇿🇦Pretoria, Gauteng, South Africa
Enhancing Care Foundation-DICRS ( Site 0381)
🇿🇦Durban, Kwazulu-Natal, South Africa
Emmed Research Incorporating ( Site 0377)
🇿🇦Pretoria, Gauteng, South Africa
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0351)
🇹🇷Ankara, Turkey
Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 0353)
🇹🇷Adana, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0355)
🇹🇷Istanbul, Turkey
Ege UTF ( Site 0356)
🇹🇷Izmir, Turkey
Dnipropetrovsk Oblast Children's Clinical Hospital ( Site 0868)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Sisli Hamide Etfal Egitim ve Arastirma Hastanesi ( Site 0358)
🇹🇷Istanbul, Turkey
SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0863)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0865)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine