Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Daptomycin · 13 trials · 15 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.
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
Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin
The volume of distribution of daptomycin before and after administration of rifampin
The elimination rate constant of daptomycin before and after administration of rifampin
The free and total peak concentrations of daptomycin before and after administration of rifampin
The free and total 24 hour concentrations of daptomycin before and after administration of rifampin
The free and total AUC from 0 to 24 hours of daptomycin before and after administration of rifampin
The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin
The percent protein binding of daptomycin before and after administration of rifampin
| 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) |
| 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. |
| Daptomycin and Rifampin | EXPERIMENTAL | Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on the first study day Drug: Rifampin Rifampin 600 mg capsules will be given orally once daily for 14 days starting on study day 2 Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on study day 15 |
| 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 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 |
| Rifampin | DRUG | - |
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 antibiotic studied for Gram-positive bacterial infections, including acute hematogenous osteomyelitis, bacterial endocarditis, bacterial pneumonia, and osteomyelitis. It is also being evaluated in pediatric patients with complicated skin and soft tissue infections and bacteremia. The drug is developed by Merck & Company, Inc. (MRK).
Daptomycin is a lipopeptide antibiotic that targets Gram-positive bacteria. It works by binding to the bacterial cell membrane and causing rapid depolarization, leading to disruption of membrane function and cell death. This mechanism makes it effective against a range of Gram-positive pathogens, including those resistant to other antibiotic classes.
Daptomycin is developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various Gram-positive infections, including pneumonia and skin infections.
Daptomycin is in Phase 3 clinical development for bacterial pneumonia, as evidenced by a completed Phase 3 trial (NCT00540072). It has also completed Phase 1 and Phase 2 trials in pediatric populations. Daptomycin is investigational and not yet approved for these indications.
Daptomycin has been studied in several completed trials, including NCT00540072 (Phase 3 for bacterial pneumonia), NCT00679835 (Phase 1 in children with Gram-positive infections), NCT01019395 (Phase 1 in children ages 3-24 months), and NCT03643952 (Phase 2 in Japanese pediatric subjects with cSSTI and bacteremia).
Yes, Daptomycin is also known as Cidecin. A Phase 3 trial (NCT00540072) compared Cidecin (daptomycin) to Rocephin (ceftriaxone) in patients with moderate to severe community-acquired bacterial pneumonia caused by S. pneumoniae.