Safety and Efficacy Study of Daptomycin in Pediatric Participants (1 to 17 Years-old) With Skin and Skin Structure Infections

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2015-002778-19-Outside-EU/EEA
• Date of registration: 29/06/2015
• Prospective Registration: Yes
• Primary sponsor: Cubist Pharmaceuticals, Inc.
• Public title: Safety and Efficacy Study of Daptomycin in Pediatric Participants (1 to 17 Years-old) With Skin and Skin Structure Infections
• Scientific title: An Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin in Pediatric Subjects Aged One to Seventeen Years With Complicated Skin and Skin Structure Infections Caused by Gram-Positive Pathogens
• Target sample size: 389
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002778-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: evaluator-blinded If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard of Care Number of treatment arms in the trial: 2

Countries of recruitment

India, Panama, United States

Contacts

• Name: Vice President, Clinical Research
• Affiliation: Cubist Pharmaceuticals, Inc.

• Name: Vice President, Clinical Research
• Affiliation: Cubist Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Written parental (or appropriate legal representative) informed consent prior to any study-related procedure not part of normal medical care
• Written participant assent (as appropriate)
• Male or female between the ages of 1 and 17 years old, inclusive
• If female of childbearing potential (defined as post-menarche), not lactating or pregnant, documented negative pregnancy test result within 48 hours prior to study medication administration and willing to practice reliable birth control measures (at the discretion of the Principal Investigator) during study treatment and for at least 28 days after study completion
• Able to comply with the protocol for the duration of the study
• Skin and skin structure infections of a complicated nature known or suspected to be caused by Gram-positive pathogen(s) that require IV antibiotic treatment. Complicated infections are defined as infections either involving deep soft tissue or requiring significant surgical intervention (such as, infected ulcers, burns, and major abscesses) or infections in which the participant has a significant underlying disease state that complicates the response to treatment. The Investigator may contact the Medical Monitor to discuss infections not meeting this definition but which otherwise appear appropriate for inclusion
• At least three of the following clinical signs and symptoms associated with the cSSSI: pain; tenderness to palpation; temperature >37.5 degrees Celsius (C) (99.5 degrees Fahrenheit [F]) oral or >38 degrees C (100.4 degrees F) rectal; white blood count (WBC) >12,000/cubic millimeter (mm^3) or =10% bands; swelling and/or induration; erythema (>1 centimeter [cm] beyond edge of wound or abscess); or pus formation
Are the trial subjects under 18? yes
Number of subjects for this age range: 389
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Investigational drug use (including daptomycin) or participation in any experimental procedure in the 30 days preceding study entry
• Known allergy/hypersensitivity to daptomycin
• Known infection caused solely by Gram-negative pathogen(s), fungus(i), or virus(es)
• Previous systemic antimicrobial therapy exceeding 24 hours in duration administered anytime during the 48 hours prior to the first dose of study drug (exception: a participant is eligible if on previous antibiotics without any clinical improvement and/or a wound culture is available and the pathogen is not sensitive to prior therapy)
• Known or suspected pneumonia, osteomyelitis, meningitis, or endocarditis
• Known bacteremia (exception: any participant enrolled in the study that is subsequently found to have a blood culture positive for bacteremia may be continued)
• Participant with current or known clinically significant abnormal laboratory test results (including electrocardiograms [ECGs]) that would expose the participant to unacceptable risk as determined by Investigator
• History of clinically significant cardiovascular, renal, hepatic, pulmonary (well-controlled asthma is acceptable), gastrointestinal, endocrine, hematological, autoimmune disease, or primary immune deficiency (unless the Investigator considers that the subject would not be at risk by participating in the study [Note: human immunodeficiency virus-infected participants must not be enrolled])
• History of or current clinically significant (at the discretion of the Investigator) muscular disease, nervous system, or seizure disorder
• Unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barre syndrome or spinal cord injury
• Known or suspected renal insufficiency (that is, estimated creatinine clearance rate [CLcr]<80 mL/min/1.73 squared meter [m^2]
• History of or current rhabdomyolysis
• History of (within 1 year prior to first dose of study drug) or current myositis
• Current septic shock
• Known or suspected creatine phosphokinase (CPK) elevation


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens

Intervention(s)

Trade Name: Cubicin®
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: DAPTOMYCIN
CAS Number: 103060-53-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: To assess the safety of age dependent doses of intravenous (IV) DAP administered for up to 14 days in comparison with standard of care (SOC) therapy in pediatric subjects aged 1 to 17 years with cSSSI caused by Gram-positive pathogens.

Primary end point(s): Evaluation of Safety: The safety of daptomycin and SOC will be evaluated by monitoring adverse events (AEs), serious
adverse events (SAEs), serum chemistry (including serum CPK level) and changes in physical and focused neurological and
other laboratory examinations.

Secondary Objective: To assess the efficacy of age-dependent doses of IV DAP administration for up to 14 days in comparison with SOC therapy in pediatric subjects aged 1 to 17 years with cSSSI caused by Gram-positive pathogens.

To evaluate the population PK of age-dependent doses of IV DAP administered for up to 14 days in pediatric subjects aged 1 to 17 years with cSSSI caused by Gram-positive pathogens.

Timepoint(s) of evaluation of this end point: Safety will be assessed from the administration of the first dose of study medication through the last follow-up visit (7-14 days after last dose of study medication). Focused neurological examinations will be done at baseline, at End-of-Therapy (EOT) and Test-of-Cure (TOC: 7-14 days after last dose of study medication). Samples for routine laboratory testing will be collected at Screening/Baseline, weekly while the subject was on therapy, at the EOT and TOC/Safety visits.

Secondary Outcome(s)

Secondary end point(s): 1).Evaluation of Post-therapy clinical response was determined by comparing the subject’s signs and symptoms at the EOT and TOC Visits to those recorded at Study Baseline as follows:
• Cure: Resolution of clinically significant signs and symptoms associated with the skin
infection present at Study Baseline.
• Improved: Partial resolution of clinical signs and symptoms of the skin infection.
• Failure: Inadequate clinical response to therapy. NOTE: if it was determined that the primary site of infection required additional antibiotic treatment, the Assessment of Clinical Response had to be a “Failure.”
2).Overall Therapeutic Response: Subjects who were deemed both clinically cured and microbiologically eradicated were
considered overall cures.
3).Microbiologic Response: For each Gram-positive pathogen and each infection, "eradicated" or "presumed eradicated" will be considered as a satisfactory microbiologic response. "Persisted," "presumed persisted," or a positive culture for a Superinfecting Pathogen (Gram-positive) at EOT through TOC will be considered as an unsatisfactory microbiologic response.
Microbiological success: All Baseline Infecting pathogens were Eradicated or Presumed Eradicated and no Superinfecting pathogen(s) (Gram-positive) were isolated post therapy.
Microbiological failure: Presence of a Persisting Pathogen or a Superinfecting pathogen (Gram-positive) post therapy (EOT through TOC).
Overall success:
This will be based on microbiologic response and clinical response at TOC (cure, improved, failure or nonevaluable) with
regard to the Investigator’s determination of the resolution or improvement of signs and symptoms.

Timepoint(s) of evaluation of this end point: 1). Evaluation of Post-therapy clinical response was determined at the Baseline, EOT, and TOC Visits
2). The assessment of Overall Therapeutic Response was made at the TOC visit.
3). Evaluation of Microbiologic Response was determined at EOT through TOC.

Secondary ID(s)

DAP-PEDS-07-03

Source(s) of Monetary Support

Cubist Pharmaceuticals, Inc.