Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Daptomycin for Injection, Cubicin
Daptomycin · 13 trials · 14 indications
Clinical improvement was based on the Investigator's overall assessment of severity of each of the 3 general symptom categories of Pain, Inflammation, and Limb Function. Based on this evaluation, a participant was considered to have met criteria for clinical improvement according to the following definition: If 3 general categories are present at baseline: at least a 1-point improvement (i.e. severe to moderate, moderate to mild, mild to absent) in at least 2 of the general categories and no worsening in the other. If 2 general categories are present at baseline: at least a 2-point improvement (i.e. severe to mild, moderate to absent) in at least 1 of the general categories and no worsening or new findings in the others OR at least a 1-point improvement in both and no new findings in the other. If 1 general category is present at baseline: at least a 2-point improvement (i.e., severe to mild, moderate to absent) in that category and no new findings in the others.
Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at end of treatment (EOT). MITT-MRSA (modified intent-to-treat - methicillin-resistant Staphylococcus aureus) was a subset of allocated participants with participants who were excluded for any of the following reasons: no MRSA isolated + any 1 of the following: failure to receive ≥1 dose of study drug, lack of all post-allocation primary and secondary endpoint data after ≥1 dose of study drug, no gram (+) coccus isolated at baseline.
Response = eradicated or presumed eradicated. Eradicated was defined as absence of the admission pathogen in a culture obtained in the absence of potentially effective antibiotics for the pathogen. Presumed eradicated was defined as no material for culture was available due to improvement of infection, but the admission pathogen was presumed to be eradicated because the participant was deemed "Cured" or "Improved" by the investigator and the participant did not receive potentially effective antibiotics for the pathogen.
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.
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.
Number of subjects with CPK \>500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
Area under the plasma concentration versus time curve from time 0 to infinity for daptomycin doses
| Arm | Type | Description |
|---|---|---|
| Daptomycin | EXPERIMENTAL | Intravenous (IV) daptomycin was dosed as follows: age 12 years to \<18 years (7 mg/kg); age 7 years to \< 12 years (9 mg/kg); age 24 months to \<7 years (12 mg/kg); age 12 months to \<24 months (12 mg/kg). Drug was infused over 60 minutes ± 10 minutes once daily followed by up to 3 dummy infusions every 6 hours (q6h) infused over 60 (± 10) min to maintain the blind. |
| Vancomycin or Nafcillin | ACTIVE_COMPARATOR | IV vancomycin (or equivalent), 10 to 15 mg/kg, was infused over 60 (± 10) minutes q6h (± 1 hour) or IV nafcillin (or β-lactam equivalent) at 100-200 mg/kg/day, in divided doses was infused over 60 (± 10) min q6h (± 1 hour) |
| MK-3009 (daptomycin) 4 mg/kg | EXPERIMENTAL | - |
| Vancomycin | ACTIVE_COMPARATOR | - |
| MK-3009 (daptomycin) 6 mg/kg | EXPERIMENTAL | - |
| Daptomycin 6 mg/kg | EXPERIMENTAL | Daptomycin (6 mg/kg every 24 hours \[q24h\]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week). |
| Daptomycin 8 mg/kg | EXPERIMENTAL | Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week). |
| Comparator | ACTIVE_COMPARATOR | Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). |
| Group 1 | EXPERIMENTAL | Group 1: Ages 13 months to 24 months inclusive. Six subjects dosed at 6 mg/kg as a 30 minute infusion. |
| Group 2 | EXPERIMENTAL | Group 2: Ages 7 months to 12 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion |
| Group 3 | EXPERIMENTAL | Group 3: Ages 3 months to 6 months inclusive: Six subjects will receive a dose of 4 mg/kg as a 30 minute infusion. |
| A | EXPERIMENTAL | 9 mg/kg of daptomycin administered during the last 30 minutes of a hemodialysis session. |
| B | EXPERIMENTAL | Post dialysis dosing |
| Hemodialysis (HD) Participants | EXPERIMENTAL | Participants will receive daptomycin 6 mg/kg by intravenous infusion (i.v.) at 48-hours intervals (with dialysis) for a total of 3 doses. |
| Continuous Ambulatory Peritoneal Dialysis (CAPD) Participants | EXPERIMENTAL | Participants will receive daptomycin 6 mg/kg, i.v., at 48-hours intervals for a total of 3 doses. |
| Name | Type | Description |
|---|---|---|
| Daptomycin | DRUG | IV daptomycin Infusion A in 12 to \<18 years old (7 mg/kg); in 7 to \< 12 year olds (9 mg/kg); in 24 months to \<7 year olds (12 mg/kg); in 12 to \<24 month olds (12 mg/kg). Infused over 60 minutes ± 10 minutes once daily followed by up to 3 dummy infusions every 6 hours (q6h) infused over 60 (± 10) min to maintain the blind. |
| Vancomycin (or equivalent) | DRUG | IV vancomycin (or equivalent) (Infusions A,B,C,D), 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour) |
| Nafcillin (or equivalent) | DRUG | IV nafcillin (or β-lactam equivalent) (Infusions A,B,C,D) at 100-200 mg/kg/day, in divided doses infused over 60 (± 10) min q6h (± 1 hour) |
| Daptomycin 4 mg/kg | DRUG | MK3009 (daptomycin) once daily by intravenous (IV) drip, 4 mg/kg for 7-14 days for skin and soft tissue infections (SSTI) |
| Comparator: vancomycin | DRUG | vancomycin 1g, twice daily (b.i.d.) by IV drip, for 7-14 days |
| Daptomycin 6 mg/kg | DRUG | MK-3009 (daptomycin) once daily by intravenous drip, 6 mg/kg for 14-42 days for septicemia or right-sided infective endocarditis |
| Daptomycin for Injection | DRUG | 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. |
| vancomycin | DRUG | 1 gram |
| teicoplanin | DRUG | 6 mg/kg; used only at UK sites |
| nafcillin | DRUG | 1-2 gram |
| oxacillin | DRUG | 1-2 gram |
| flucloxacillin | DRUG | 1-2 mg |
Inclusion Criteria: * Obtain Informed Consent; * Be 1 year to \< 18 years old; a stepwise approach will be implemented to gate enrollment as follows: enrollment will begin with children aged 2-17 years; after an external Drug Safety Monitoring Board (DSMB) review, enrollment will be broadened to 1-...
Daptomycin is a small molecule antibacterial drug developed by Merck & Company, Inc. (MRK). It is being studied in Phase 3 clinical development for Gram-positive bacterial infections, including acute hematogenous osteomyelitis, bacteremia, bacterial endocarditis, and infections in patients with end-stage renal disease.
Daptomycin has been evaluated in a Phase 3 trial for acute hematogenous osteomyelitis in pediatric participants. The study compared daptomycin to an active comparator in 149 randomized, double-blind participants aged 1 year and older. The trial, NCT01922011, has been completed.
Daptomycin is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck conducted the clinical development program for the drug, including pediatric studies in acute hematogenous osteomyelitis, complicated skin and soft tissue infections, bacteremia, and renal impairment.
Daptomycin has reached Phase 3 clinical development. A Phase 3 trial in pediatric acute hematogenous osteomyelitis has been completed, and additional completed studies include Phase 2 and Phase 1 trials. Daptomycin remains an investigational therapy in the indications studied.
Completed Daptomycin trials include NCT01922011, a Phase 3 study in pediatric acute hematogenous osteomyelitis with 149 participants, and NCT03643952, a Phase 2 study in Japanese pediatric subjects with complicated skin and soft tissue infections and bacteremia. Phase 1 studies NCT01019395 and NCT00882557 evaluated pediatric pharmacokinetics and dialysis dosing.
Daptomycin is also referred to as Daptomycin for Injection, Daptomycin 4 mg/kg, and Daptomycin/kg. These names describe the same antibacterial agent developed by Merck & Company, Inc. under the code MK-3009, and they appear across its clinical trial program.