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

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Completed; Phase 4

Conditions: Skin Diseases, Infectious

Treatments: Drug: Standard of Care (SOC); Drug: Daptomycin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00711802

DAP-PEDS-07-03 (Other Identifier)

3009-017

Details and patient eligibility

About

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and pharmacokinetics (PK) of daptomycin in pediatric subjects ages 1 to 17 years, inclusive, with complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens.

Full description

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and PK of daptomycin in pediatric participants ages 1 to 17 years, inclusive, with cSSSI caused by Gram-positive pathogens. Participants will be enrolled into age groups and given age-dependent doses over a period of up to 14 days. Participants will be stratified by age group to receive either daptomycin or SOC (recommended as vancomycin, clindamycin or semisynthetic penicillin) in a ratio of 2:1, respectively. Participants may continue on oral therapy following completion of IV study drug administration and provided that the participant meets all criteria for conversion to oral therapy, including clear clinical improvement and availability of an oral agent to which the pathogen is susceptible. The choice of oral therapy will be left to the discretion of the Investigator. February 11, 2015 released from post marketing requirement to include subjects aged 3 months - < 1 year. Ref ID: 3701325

Enrollment: 396 patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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396 participants in 2 patient groups

Daptomycin

Experimental group

Description:

Administered intravenously (IV) every 24 hours for up to 14 days at the following age-dependent dosages. Participants ages 7 to 17 years: daptomycin was dissolved in a volume of 50 milliliters (mL) 0.9% sodium chloride for injection over 30 minutes (min) with an infusion rate of 1.67 mL/min. Participants 1 to 6 years-old: daptomycin was dissolved in a volume of 25 mL 0.9% sodium chloride for injection over 60 min with an infusion rate was 0.42 mL/min. Age Group 1 (for ages 12 to 17 years): 5 milligrams/kilogram (mg/kg) Age Group 2 (for ages 7 to 11 years): 7 mg/kg Age Group 3 (for ages 2 to 6 years): 9 mg/kg Age Group 4 (for ages 1 to \<2 years): 10 mg/kg

Treatment:

Drug: Daptomycin

Standard of Care (SOC)

Active Comparator group

Description:

The comparator agent for this study was the SOC treatment and dosage deemed appropriate by the Investigator. The recommended SOC agents were IV vancomycin, IV clindamycin, and IV semisynthetic penicillins every 24 hours for up to 14 days.

Treatment:

Drug: Standard of Care (SOC)