Safety, Efficacy, and Pharmacokinetics (PK) of Daptomycin (MK-3009) in Japanese Pediatric Subjects With Complicated Skin and Soft Tissue Infections (cSSTI) and Bacteremia (MK-3009-029)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, efficacy and pharmacokinetic (PK) parameters of daptomycin for injection in Japanese pediatric participants aged 1 to 17 years with complicated skin and soft tissue infection (cSSTI) or bacteremia caused by gram-positive cocci.

Official Title
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A Phase II Open-Label, Single-arm Clinical Trial to Study the Safety, Efficacy and Pharmacokinetics of MK-3009 (Daptomycin) in Japanese Pediatric Participants Aged 1 to 17 Years With Complicated Skin and Soft Tissue Infections or Bacteremia Caused by Gram-positive Cocci

Conditions
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Bacteremia, Soft Tissue Infections, Skin Diseases, Infectious

Intervention / Treatment
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* Drug: Daptomycin for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Requires treatment for cSSTI or bacteremia. Is male or female Japanese aged ≥ 1 to ≤ 17 years on the day of signing informed consent. As a male participant, has agreed to use contraception during the treatment period and for at least 14 days after the last dose of study treatment and refrain from donating sperm during this period. As a female participant, has agreed to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 14 days after the last dose of study treatment. Has agreed to allow any bacterial isolates obtained from protocol-required specimens related to the current infection to be provided the Central Microbiology Reference Laboratory for study-related microbiological testing, long-term storage, and other future testing. cSSTI Participants Has cSSTI known or suspected to be caused by gram-positive cocci that requires intravenous antibiotic treatment and diagnosed with either Gram stain or culture. Has at least 3 of the following clinical signs and symptoms associated with the cSSTI: pain, tenderness to palpation, temperature >37.0°C axillary or >37.5°C oral or >38.0° C rectal, forehead, or aural, white blood count (WBC) >12,000/mm^3 or ≥10% bands, swelling and/or induration, erythema (>1 cm beyond edge of wound or abscess), pus formation, CRP > upper limited of normal. Bacteremia Participants Have proven bacteremia with pathogen identification of gram-positive cocci at least one blood culture bottle by conventional culture methods or by a rapid diagnostic test in screening period. Have probable bacteremia with a blood culture result demonstrating gram-positive cocci by Gram stain in screening period. Exclusion Criteria: Has received previous systemic antimicrobial therapy that is effective against gram-positive cocci and exceeding 72 hours duration administered at any time during the 96 hours prior to the first dose of study drug. Has a known infection caused solely by gram-negative pathogen(s), fungus(i) or virus(es). Has pneumonia (septic emboli in the lung is not an exclusion if clear evidence of source of infection is other than lungs), empyema, meningitis, endocarditis, or osteoarticular infection. Has a history of or current rhabdomyolysis. Is anticipated to require non-study systemic antibiotics that may be potentially effective against gram-positive pathogen(s). Has shock or hypotension unresponsive to fluids or vasopressors for ≥ 4 hours. Has significant allergy/hypersensitivity or intolerance to daptomycin. Has renal insufficiency. Has a history of clinically significant (as assessed by the Investigator) muscular disease, nervous system or seizure disorder, including unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barre or spinal cord injury; previous uncomplicated febrile seizure allowed. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might expose the participant to risk by participating in the trial, confound the results of the trial, or interfere with the participant's participation for the full duration of the trial. Is a female who is pregnant or is expecting to conceive (or is a male partner of a female who is expecting to conceive), is breastfeeding, or plans to breastfeed prior to completion of the study. Is currently participating in, or has participated in, any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of the presentation or during the previous 30 days prior to screening or is anticipated to participate in such a clinical study during the course of this trial. Has previously participated in this study at any time. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this study.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daptomycin<br>Participants aged 1 to 17 years old with cSSTI or bacteremia will receive daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia. | Drug: Daptomycin for Injection<br>* Once daily administration of 5, 7, 9, 10, or 12 mg/kg intravenous (IV) daptomycin infused with 25-50 mL saline over 30-60 minutes depending upon infection type and age level.<br>* Other names: MK-3009;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Adverse Event | An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. | Up to 56 days | 
| Percentage of Participants That Discontinued Study Treatment Due to an Adverse Event (AE) | An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. | Up to 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections Who Experienced Clinical Success | Clinical success in participants with MRSA infections was defined as either Cure - Resolution of clinically significant signs and symptoms associated with admission infection and no further antibiotic therapy required, OR Improved- partial resolution of clinical signs or symptoms of infection with no further antibiotic therapy required. | Up to 7 days following end of treatment (up to 49 days) | 
| Percentage of Participants With MRSA Infections Who Experienced a Microbiological Response | Participant-level microbiological response in participants with MRSA infections at baseline is defined as absence or presumed absence of all baseline infecting pathogens AND no gram-positive superinfection or gram-positive new infection, as assessed by infection site specimen culture or blood culture. | Up to 7 days following end of treatment (up to 49 days) | 
| Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin | Blood samples were collected at pre-specified time points to determine the AUC0-24 of daptomycin. | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 
| Maximum Plasma Concentration (Cmax) of Daptomycin | Blood samples were collected at pre-specified timepoints to determine Cmax of daptomycin. | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 
| Time to Maximum Plasma Concentration (Tmax) of Daptomycin | Blood samples were collected at pre-specified time points to determine Tmax of daptomycin | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 
| Body Weight Adjusted Clearance (CLss/wt) of Daptomycin | Blood samples were collected at pre-specified time points to determine CLss/wt of daptomycin at steady state. | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 
| Volume of Distribution at Steady State (Vss) of Daptomycin | Blood samples were collected at pre-specified time points to determine Vss (mL) of daptomycin. | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 
| Apparent Terminal Half-Life (t½) of Daptomycin | Blood samples were collected at pre-specified time points to determine the t½ of daptomycin. | Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methicillin-resistant S. aureus (MRSA) infections, complicated skin and soft tissue infections (cSSTI)