Clinical trial NCT03643952: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bacteremia
Soft Tissue Infections
Skin Diseases, Infectious
Keywords: methicillin-resistant S. aureus (MRSA) infections
complicated skin and soft tissue infections (cSSTI)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-08-23
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With an Adverse Event
timeFrame: Up to 56 days
measure: Percentage of Participants That Discontinued Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to 42 days
Secondary outcomes:
measure: Percentage of Participants With Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections Who Experienced Clinical Success
timeFrame: Up to 7 days following end of treatment (up to 49 days)
measure: Percentage of Participants With MRSA Infections Who Experienced a Microbiological Response
timeFrame: Up to 7 days following end of treatment (up to 49 days)
measure: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
measure: Maximum Plasma Concentration (Cmax) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
measure: Time to Maximum Plasma Concentration (Tmax) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
measure: Body Weight Adjusted Clearance (CLss/wt) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
measure: Volume of Distribution at Steady State (Vss) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
measure: Apparent Terminal Half-Life (t½) of Daptomycin
timeFrame: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Japan Community Health Care Organization Chukyo Hospital ( Site 0030)
state: Aichi
city: Kitakyushu
country: Japan
facility: Japan Community Health care Organization Kyushu Hospital ( Site 0016)
state: Fukuoka
city: Maebashi
country: Japan
facility: Maebashi Red Cross Hospital ( Site 0012)
state: Gunma
city: Kobe
country: Japan
facility: Kobe University Hospital ( Site 0015)
state: Hyogo
city: Zentsuji
country: Japan
facility: Shikoku Medical Center for Children and Adults ( Site 0027)
state: Kagawa
city: Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital ( Site 0023)
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Children's Medical Center ( Site 0025)
state: Kanagawa
city: Tsu
country: Japan
facility: National Hospital Organization National Mie Hospital ( Site 0002)
state: Mie
city: Beppu
country: Japan
facility: National Hospital Organization Beppu Medical Center ( Site 0003)
state: Oita
city: Fuchu
country: Japan
facility: Tokyo Metropolitan Children's Medical Center ( Site 0004)
state: Tokyo
city: Chiba
country: Japan
facility: Chiba University Hospital ( Site 0005)
city: Chiba
country: Japan
facility: Chiba Children's Hospital ( Site 0024)
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center ( Site 0018)
city: Osaka
country: Japan
facility: Osaka City General Hospital ( Site 0020)
city: Saitama
country: Japan
facility: Saitama City Hospital ( Site 0008)
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital ( Site 0029)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Iwata S, Koyama H, Murata Y. Efficacy and safety of daptomycin in Japanese pediatric participants with complicated skin and soft tissue infections or bacteremia caused by gram-positive cocci. J Infect Chemother. 2022 Mar;28(3):406-412. doi: 10.1016/j.jiac.2021.11.019. Epub 2021 Dec 15.