Trial Outcomes & Findings for Safety, Efficacy, and Pharmacokinetics (PK) of Daptomycin (MK-3009) in Japanese Pediatric Subjects With Complicated Skin and Soft Tissue Infections (cSSTI) and Bacteremia (MK-3009-029) (NCT NCT03643952)

NCT ID: NCT03643952

Last Updated: 2022-05-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: Up to 56 days
• Results posted on: 2022-05-13

Participant Flow

Participant milestones

Measure	Daptomycin Participants aged 1 to 17 years old with complicated skin and soft tissue infections (cSSTI) or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.
Overall Study STARTED	18
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Daptomycin Participants aged 1 to 17 years old with complicated skin and soft tissue infections (cSSTI) or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.
Overall Study Lack of Efficacy	1

Baseline Characteristics

Safety, Efficacy, and Pharmacokinetics (PK) of Daptomycin (MK-3009) in Japanese Pediatric Subjects With Complicated Skin and Soft Tissue Infections (cSSTI) and Bacteremia (MK-3009-029)

Baseline characteristics by cohort

Measure	Daptomycin n=18 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.
Age, Continuous	6.9 Years STANDARD_DEVIATION 5.1 • n=5 Participants
Age, Customized Newborns (0-27 days)	0 Participants n=5 Participants
Age, Customized Infants and toddlers (28 days-23 months)	5 Participants n=5 Participants
Age, Customized Children (2-11 years)	9 Participants n=5 Participants
Age, Customized Adolescents (12-17 years)	4 Participants n=5 Participants
Age, Customized Adults (18-64 years)	0 Participants n=5 Participants
Age, Customized From 65-84 years	0 Participants n=5 Participants
Age, Customized 85 years and over	0 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 56 days

Population: All enrolled participants who received at least one dose of daptomycin

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.

Outcome measures

Measure	Daptomycin n=18 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Percentage of Participants With an Adverse Event	55.6 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to 42 days

Population: All enrolled participants who received at least one dose of daptomycin

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.

Outcome measures

Measure	Daptomycin n=18 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Percentage of Participants That Discontinued Study Treatment Due to an Adverse Event (AE)	0 Percentage of Participants	—

SECONDARY outcome

Timeframe: Up to 7 days following end of treatment (up to 49 days)

Population: All enrolled participants with cSSTI or bacteremia who had a positive culture of MRSA at baseline and received at least one dose of study treatment

Clinical success in participants with MRSA infections was defined as either "Cure" - Resolution of clinically significant signs and symptoms associated with admission infection and no further antibiotic therapy required, OR "Improved"- partial resolution of clinical signs or symptoms of infection with no further antibiotic therapy required.

Outcome measures

Measure	Daptomycin n=7 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=1 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Percentage of Participants With Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections Who Experienced Clinical Success	85.7 Percentage of Participants Interval 42.1 to 99.6	100 Percentage of Participants Interval 2.5 to 100.0

SECONDARY outcome

Timeframe: Up to 7 days following end of treatment (up to 49 days)

Population: All enrolled participants with cSSTI or bacteremia who had a positive culture of MRSA at baseline and received at least one dose of study treatment

Participant-level microbiological response in participants with MRSA infections at baseline is defined as absence or presumed absence of all baseline infecting pathogens AND no gram-positive superinfection or gram-positive new infection, as assessed by infection site specimen culture or blood culture.

Outcome measures

Measure	Daptomycin n=7 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=1 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Percentage of Participants With MRSA Infections Who Experienced a Microbiological Response	71.4 Percentage of Participants Interval 29.0 to 96.3	100 Percentage of Participants Interval 2.5 to 100.0

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive intravenous (IV) infusions of study treatment, had at least 1 pharmacokinetic (PK) sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified time points to determine the AUC0-24 of daptomycin.

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=3 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin Age Category 1-<2 years	574 µg·hr/mL Standard Deviation 99.1	502 µg·hr/mL Standard Deviation 0
Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin Age Category 2-6 years	431 µg·hr/mL Standard Deviation 53.6	—
Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin Age Category 7-11 years	409 µg·hr/mL Standard Deviation 143	599 µg·hr/mL Standard Deviation 0
Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24hr) of Daptomycin Age Category 12-17 years	316 µg·hr/mL Standard Deviation 18.2	422 µg·hr/mL Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive IV infusions of study treatment, had at least 1 PK sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified timepoints to determine Cmax of daptomycin.

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=4 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Maximum Plasma Concentration (Cmax) of Daptomycin Age Category 1-<2 years	91.7 μg/mL Standard Deviation 6.66	104 μg/mL Standard Deviation 8.70
Maximum Plasma Concentration (Cmax) of Daptomycin Age Category 2-6 years	80.3 μg/mL Standard Deviation 4.48	—
Maximum Plasma Concentration (Cmax) of Daptomycin Age Category 7-11 years	64.4 μg/mL Standard Deviation 15.1	73.1 μg/mL Standard Deviation 0
Maximum Plasma Concentration (Cmax) of Daptomycin Age Category 12-17 years	49.3 μg/mL Standard Deviation 1.33	94.0 μg/mL Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive IV infusions of study treatment, had at least 1 PK sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified time points to determine Tmax of daptomycin

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=4 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Time to Maximum Plasma Concentration (Tmax) of Daptomycin Age Category 1-<2 Years	1.33 Hours Interval 1.33 to 1.37	1.27 Hours Interval 1.2 to 1.33
Time to Maximum Plasma Concentration (Tmax) of Daptomycin Age Category 2-6 Years	1.23 Hours Interval 1.12 to 1.27	—
Time to Maximum Plasma Concentration (Tmax) of Daptomycin Age Category 7-11 Years	0.833 Hours Interval 0.783 to 1.0	0.800 Hours Interval 0.8 to 0.8
Time to Maximum Plasma Concentration (Tmax) of Daptomycin Age Category 12-17 Years	0.750 Hours Interval 0.75 to 0.75	0.733 Hours Interval 0.733 to 0.733

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive IV infusions of study treatment, had at least 1 PK sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified time points to determine CLss/wt of daptomycin at steady state.

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=3 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Body Weight Adjusted Clearance (CLss/wt) of Daptomycin Age Category 1-<2 Years	17.8 mL/hr/kg Standard Deviation 2.86	23.9 mL/hr/kg Standard Deviation 0
Body Weight Adjusted Clearance (CLss/wt) of Daptomycin Age Category 2-6 Years	21.1 mL/hr/kg Standard Deviation 2.69	—
Body Weight Adjusted Clearance (CLss/wt) of Daptomycin Age Category 7-11 Years	19.4 mL/hr/kg Standard Deviation 8.27	15.0 mL/hr/kg Standard Deviation 0
Body Weight Adjusted Clearance (CLss/wt) of Daptomycin Age Category 12-17 Years	15.8 mL/hr/kg Standard Deviation 0.917	16.6 mL/hr/kg Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive IV infusions of study treatment, had at least 1 PK sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified time points to determine Vss (mL) of daptomycin.

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=3 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Volume of Distribution at Steady State (Vss) of Daptomycin Age Category 1-<2 Years	1146 mL Standard Deviation 299	1918 mL Standard Deviation 0
Volume of Distribution at Steady State (Vss) of Daptomycin Age Category 2-6 Years	1753 mL Standard Deviation 486	—
Volume of Distribution at Steady State (Vss) of Daptomycin Age Category 7-11 Years	3929 mL Standard Deviation 2032	4013 mL Standard Deviation 0
Volume of Distribution at Steady State (Vss) of Daptomycin Age Category 12-17 Years	6414 mL Standard Deviation 1086	5106 mL Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment

Population: All enrolled participants who received at least 3 consecutive IV infusions of study treatment, had at least 1 PK sample following study drug administration, and did not have any protocol violations affecting the PK profile

Blood samples were collected at pre-specified time points to determine the t½ of daptomycin.

Outcome measures

Measure	Daptomycin n=14 Participants Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.	Daptomycin (MRSA With Bacteremia) n=3 Participants Participants aged 1 to 17 years old with bacteremia and a positive culture of MRSA at baseline received daptomycin intravenously every 24 hours for 5-42 days.
Apparent Terminal Half-Life (t½) of Daptomycin Age Category 1-<2 Years	4.94 Hours Standard Deviation 0.460	4.46 Hours Standard Deviation 0
Apparent Terminal Half-Life (t½) of Daptomycin Age Category 2-6 Years	3.87 Hours Standard Deviation 0.514	—
Apparent Terminal Half-Life (t½) of Daptomycin Age Category 7-11 Years	5.07 Hours Standard Deviation 1.09	5.85 Hours Standard Deviation 0
Apparent Terminal Half-Life (t½) of Daptomycin Age Category 12-17 Years	5.71 Hours Standard Deviation 0.942	3.98 Hours Standard Deviation 0

Adverse Events

Daptomycin

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Daptomycin n=18 participants at risk Participants aged 1 to 17 years old with cSSTI or bacteremia received daptomycin intravenously every 24 hours for either 5-14 days for cSSTI or for 5-42 days for bacteremia.
Gastrointestinal disorders Constipation	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Gastrointestinal disorders Enterocolitis	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Gastrointestinal disorders Gastrointestinal mucosal disorder	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
General disorders Catheter site related reaction	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
General disorders Chills	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
General disorders Infusion site swelling	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
General disorders Injection site pain	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
General disorders Pyrexia	11.1% 2/18 • Number of events 2 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Infections and infestations Gastroenteritis viral	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Infections and infestations Genital candidiasis	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Infections and infestations Nasopharyngitis	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Investigations Alanine aminotransferase increased	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Investigations Platelet count increased	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Investigations Weight decreased	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Skin and subcutaneous tissue disorders Acne	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Skin and subcutaneous tissue disorders Alopecia	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Skin and subcutaneous tissue disorders Rash	11.1% 2/18 • Number of events 2 • Up to 56 days All enrolled participants who received at least one dose of daptomycin
Vascular disorders Hypertension	5.6% 1/18 • Number of events 1 • Up to 56 days All enrolled participants who received at least one dose of daptomycin

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
• Publication restrictions are in place

Restriction type: OTHER