3009-017

Cubist Pharmaceuticals, Inc.

65 Hayden Avenue, Lexington,, United States, 02421

Medical Director, Cubist Pharmaceuticals, Inc., 001 781860-8660,

Medical Director, Cubist Pharmaceuticals, Inc., 001 781860-8660,

No

No

Yes

Final

02 Mar 2015

Yes

01 Oct 2013

Yes

01 Oct 2013

Yes

To assess the safety of age dependent doses of intravenous (IV) daptomycin administered for up to 14 days in comparison with standard of care (SOC) therapy in pediatric subjects aged 1 to 17 years with complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens.

This study was conducted in compliance with institutional review board (IRB)/independent ethics committee (IEC) and International Conference on Harmonisation (ICH) E6 Good Clinical Practice (GCP): Consolidated Guideline, and any local regulations.

03 Sep 2008

No

Yes

India: 123

United States: 273

396

0

0

0

0

45

234

117

0

0

0

Overall Study (overall period)

Randomised - controlled

This was an evaluator-blinded study. The maintenance of the study blind was critical for an unbiased review of the safety and efficacy of the study drug. Therefore a site blinding plan was developed at each site detailing exactly how the blind was maintained throughout the study. Prior to study start at each site, a physician was designated the blinded Investigator. The unblinded evaluator was responsible for all other study-related procedures and assessments and followed the subject daily.

Yes

Daptomycin

Cubicin

Injection

Intravenous use

Administered intravenously (IV) every 24 hours for up to 14 days at the following age-dependent dosages. Subjects ages 7 to 17 years: daptomycin was dissolved in a volume of 50 millilitres (mL) 0.9% sodium chloride for injection over 30 minutes (min) with an infusion rate of 1.67 mL/min. Subjects 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

Standard of Care

Injection

Intravenous use

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.

Overall Study (overall period)

Daptomycin

Subjects who received at least 1 dose of study drug.

Standard of Care (SOC)

Subjects who received at least 1 dose of study drug.

Age Group 1: Daptomycin

Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years

Age Group 1: Standard of Care (SOC)

SOC: 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. Age Group 1: Participants ages 12 to 17 years

Age Group 2: Daptomycin

Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years

Age Group 2: SOC

SOC: 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. Age Group 2: Participants ages 7 to 11 years

Age Group 3: Daptomycin

Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years

Age Group 3: SOC

SOC: 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. Age Group 3: Participants ages 2 to 6 years

Age Group 4: Daptomycin

Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years

Age Group 4: SOC

SOC: 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. Age Group 4: Participants ages 1 to <2 years

Daptomycin

Standard of Care (SOC)

Daptomycin

Subjects who received at least 1 dose of study drug.

Standard of Care (SOC)

Subjects who received at least 1 dose of study drug.

Age Group 1: Daptomycin

Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years

Age Group 1: Standard of Care (SOC)

SOC: 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. Age Group 1: Participants ages 12 to 17 years

Age Group 2: Daptomycin

Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years

Age Group 2: SOC

SOC: 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. Age Group 2: Participants ages 7 to 11 years

Age Group 3: Daptomycin

Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years

Age Group 3: SOC

SOC: 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. Age Group 3: Participants ages 2 to 6 years

Age Group 4: Daptomycin

Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years

Age Group 4: SOC

SOC: 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. Age Group 4: Participants ages 1 to <2 years

A TEAE was defined as any treatment-emergent adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing adverse AEs that were aggravated in severity or frequency during the dosing period. The percentage of participants with at least 1 TEAE is presented.

Primary

Baseline (Day 1) through 14 days after last dose of study drug

The assessment of therapeutic response was determined by comparing a participant’s signs and symptoms at the test of cure visit (up to 14 days after last dose) to those recorded at baseline. Participants were classified as “Success” or “Failure” by combining their clinical and microbiological efficacy responses. Resolution of clinically significant signs and symptoms associated with the skin infection present at study baseline was considered “Success” by the Investigator. These participants were deemed both clinically cured and microbiologically eradicated. For participants whose clinical course could not be clearly defined as improved, a clinical outcome of “Failure” was rendered. In addition, if it was determined that the primary site of infection required additional antibiotic treatment, the assessment of clinical response was “Failure.” If the Investigator was unable to determine a response because the participant was lost to follow-up, the assessment was “Unable to evaluate.”

Secondary

Test of cure visit--14 days after last dose of study drug

Success rate was calculated as the number of subjects with clinical success at each visit divided by the total number of subjects with outcome at that visit. The difference in success rate was calculated as success rate for daptomycin minus rate for standard of care.

Daptomycin v Standard of Care (SOC)

315

Pre-specified

0.9

2-sided

Participants who volunteered for PK sampling had a blood sample collected for analysis at the following time points: Age Group 1; Day 3: Predose, 0.25 hour (hr), 1 hr, 4 hr, and12 hr postdose. Age Group 2; Day 3: Predose, 0.25 hr, 1 hr, 6 hr, and 10 hr postdose. Age Group 3; Day 1, 2, or 3: Predose, 0.25 hr, 1 hr, 6 hr, and 8 hr postdose. Age Group 4; Day 1, 2, or 3: 0, 1, 2, 4, and 6 hr relative to end of infusion. Due to limited PK samples, where measures could not be calculated, a "0" is reported. Due to limited PK samples, PK parameters were computed using the mean concentration-time profile during a sampling interval. As a result, no variability could be calculated for data where "0" is reported.

Secondary

Predose and 5 timepoints according to age group (up to 12 hours postdose).

Subjects were monitored for adverse events from Screening (within 48 hours of 1st dose of study drug) through the last study evaluation visit (7-14 days after the last dose of study drug).

11.0

Age Group 4: Daptomycin

Age Group 2: Daptomycin

Standard of Care

Age Group 1: Daptomycin

Age Group 3: Daptomycin