Clinical Trial Results:
A Phase II Open-Label, Single-arm Clinical Trial to Study the Safety, Efficacy and Pharmacokinetics of MK-3009 (Daptomycin) in Japanese Pediatric Participants Aged 1 to 17 Years with Complicated Skin and Soft Tissue Infections or Bacteremia caused by Gram-positive cocci
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Summary
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EudraCT number |
2020-001576-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
13 Jul 2020
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Results information
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Results version number |
v2(current) |
This version publication date |
14 May 2021
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First version publication date |
25 Dec 2020
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-3009-029
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03643952 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Japic-CTI: 184155 | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jul 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of this study is to assess the safety, efficacy and pharmacokinetic (PK) parameters of daptomycin for injection in Japanese pediatric participants aged 1 to 17 years with complicated skin and soft tissue infection (cSSTI) or bacteremia caused by Gram-positive cocci.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statues and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
5
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Children (2-11 years) |
9
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Adolescents (12-17 years) |
4
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
This trial enrolled participants requiring treatment for cSSTI or bacteremia caused by Gram-positive cocci. Additional inclusion criteria applied. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Daptomycin-cSSTI or Bacteremia: Age 1-17 | ||||||||||
Arm description |
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 | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Daptomycin for injection
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Investigational medicinal product code |
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Other name |
MK-3009
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
Daptomycin-cSSTI or Bacteremia: Age 1-17
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Reporting group description |
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Daptomycin-cSSTI or Bacteremia: Age 1-17
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Reporting group description |
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 | ||
Subject analysis set title |
cSSTI
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants diagnosed with complicated skin and soft tissue infection (cSSTI) received daptomycin intravenously every 24 hours for 5-14 days
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Subject analysis set title |
Bacteremia
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants diagnosed with bacteremia received daptomycin intravenously every 24 hours for 5-42 days
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Subject analysis set title |
MRSA with cSSTI
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All enrolled participants with cSSTI who had a positive culture of methicillin-resistant staphylococcus aureus (MRSA) at baseline and received at least one dose of study treatment.
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Subject analysis set title |
MRSA with Bacteremia
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All enrolled participants with bacteremia who had a positive culture of MRSA at baseline and received at least one dose of study treatment.
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End point title |
Percentage of Participants with an Adverse Event [1] | ||||||||
End point description |
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. The analysis population included all enrolled participants who received at least one dose of daptomycin.
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End point type |
Primary
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End point timeframe |
Up to 56 days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no between-group statistical analyses for this endpoint as the trial was conducted as a single-arm study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants that Discontinued Study Treatment Due to an Adverse Event (AE) [2] | ||||||||
End point description |
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. The percentage of participants discontinued from the study due to an AE is reported. The analysis population included all enrolled participants who received at least one dose of daptomycin.
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End point type |
Primary
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End point timeframe |
Up to 42 days
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no between-group statistical analyses for this endpoint as the trial was conducted as a single-arm study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Methicillin-Resistant Staphylococcus Aureus (MRSA) Infections Who Experienced Clinical Success | ||||||||||||
End point description |
Clinical success in participants with MRSA 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. The analysis population included 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.
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End point type |
Secondary
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End point timeframe |
Up to 7 days following end of treatment (Up to 49 days)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants with MRSA Infections Who Experienced a Microbiological Response | ||||||||||||
End point description |
Participant-level microbiological response is defined as absence or presumed absence of all baseline infecting pathogens AND no gram-positive superinfection or gram-positive new infection. The analysis population included 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.
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End point type |
Secondary
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End point timeframe |
Up to 7 days following end of treatment (up to 49 days)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area Under the Concentration Time Curve from Time 0 to 24 Hours (AUC0-24) of Daptomycin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified time points to determine the AUC0-24 of daptomycin. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Mean Maximum Concentration (Cmax) of Daptomycin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified timepoints to determine Cmax of daptomycin. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Time to Maximum Plasma Concentration (Tmax) of Daptomcyin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified time points to determine the Tmax of daptomycin. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomcyin treatment
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Body Weight Adjusted Clearance at Steady State (CLss/wt) of Daptomycin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified time points to determine CLss/wt of daptomycin at steady state. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Volume of Distribution at Steady State (Vss) of Daptomcyin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified time points to determine Vss (mL) of daptomycin. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
On Day 3 of study drug administration- pre dose, 15 minutes, 1 hour, 4 hours, and 12 hours after the end of infusion.
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Apparent Terminal Half-life (t½) of Daptomcyin | ||||||||||||||||||||||||
End point description |
Blood samples were collected at pre-specified time points to determine the t½ of daptomycin. The analysis population included all enrolled participants who received at least 3 consecutive 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.
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End point type |
Secondary
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End point timeframe |
Pre-dose and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose on Day 3 of daptomycin treatment
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 56 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Daptomycin
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was concluded due to the difficulty of enrolling pediatric patients into the study during the COVID-19 pandemic. This study concluded enrollment with 18 participants, versus the 20 that were originally planned. | |||
