Clinical Trial Results:
A Multicenter, Open, Sequential Dose-Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 2 Separate Doses of Caspofungin Acetate in Children Between the Ages of 3 to 24 Months With New Onset Fever and Neutropenia
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Summary
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EudraCT number |
2014-005030-54 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
31 Jul 2006
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Feb 2016
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First version publication date |
15 Jul 2015
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Other versions |
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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-0991-042
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00292071 | ||
WHO universal trial number (UTN) |
- | ||
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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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000010-PIP01-07 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jul 2006
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2006
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2006
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This study was an open-label, multicenter study to evaluate the safety, tolerability, and pharmacokinetics of caspofungin in clinically stable children with fever and neutropenia between the ages of 3 to 24 months.
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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 statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
Caspofungin was to be administered daily until the participant recovered from the neutropenic episode. However, if the participant remained febrile and neutropenic after 4 days of therapy, caspofungin was to be discontinued and the participant was to be started thereafter on a standard empirical antifungal regimen with intravenous amphotericin B (either conventional deoxycholate or a lipid formulation). Similarly, if the participant developed a proven or probable breakthrough invasive fungal infection, caspofungin was to be discontinued and an intravenous (IV) formulation of amphotericin B was to be administered.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Apr 2005
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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 |
United States: 9
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Worldwide total number of subjects |
9
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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) |
9
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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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 |
The study enrolled clinically stable, immunocompromised children between the ages of 3 and 24 months with a history of underlying hematological or solid organ malignancies, hematopoietic stem cell transplantation (including bone marrow or peripheral stem cell transplantation), or aplastic anemia, and new onset fever and neutropenia. | ||||||||||
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Pre-assignment
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Screening details |
Nine participants were screened and 9 were enrolled in the study. Only the caspofungin 50 mg/m^2/day regimen was enrolled. Due to enrollment difficulties the study was halted prior to enrollment of any participants in the caspofungin 70 mg/m^2/day regimen. | ||||||||||
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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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Caspofungin 50 mg/m^2/day | ||||||||||
Arm description |
Participants received caspofungin 50 mg/m^2/day in a 1-hour intravenous infusion for a minimum of 4 days and a maximum of 28 days. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Caspofungin
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Investigational medicinal product code |
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Other name |
CANCIDAS™, MK-0991
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Caspofungin acetate 50 mg/m^2/day in a 1-hour intravenous infusion for a minimum of 4 days and a maximum of 28 days. Infusion employed a pediatric syringe or ambulatory pump.
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Baseline characteristics reporting groups
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Reporting group title |
Caspofungin 50 mg/m^2/day
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Reporting group description |
Participants received caspofungin 50 mg/m^2/day in a 1-hour intravenous infusion for a minimum of 4 days and a maximum of 28 days. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Caspofungin 50 mg/m^2/day
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Reporting group description |
Participants received caspofungin 50 mg/m^2/day in a 1-hour intravenous infusion for a minimum of 4 days and a maximum of 28 days. | ||
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End point title |
Area Under the Plasma Concentration Curve of Caspofungin up to 24 Hours (AUC0-24) on Day 1 [1] | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method.
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End point type |
Primary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 1 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the 1-hour infusion.
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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: This was a single-arm study; therefore, no statistical analysis was performed for this endpoint. |
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| Notes [2] - Participants who received the Day 1 infusion and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Caspofungin at One Hour (C1hr) on Day 1 | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method.
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End point type |
Secondary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 1 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the 1-hour infusion.
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| Notes [3] - Participants who received the Day 1 infusion and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Caspofungin at 24 Hours (C24hr) on Day 1 | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method.
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End point type |
Secondary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 1 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the 1-hour infusion.
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| Notes [4] - Participants who received the Day 1 infusion and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Plasma Concentration Curve of Caspofungin up to 24 Hours (AUC0-24) on Day 3 to 14 | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method. Values reported are for Day 4 or time-average geometric mean of all values obtained between Day 3 and 14.
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End point type |
Secondary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 3 through 14 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the daily 1-hour infusion.
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| Notes [5] - Participants who received >=1 infusion on Days 3 - 14 and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Caspofungin at One Hour (C1hr) on Day 3 to 14 | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method. Values reported are for Day 4 or time-average geometric mean of all values obtained between Day 3 and 14.
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End point type |
Secondary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 3 through 14 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the daily 1-hour infusion.
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| Notes [6] - Participants who received >=1 infusion on Days 3 - 14 and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma Concentration of Caspofungin at 24 Hours (C24hr) on Day 3 to 14 | ||||||||
End point description |
Plasma caspofungin concentrations were measured with a high-performance liquid chromatography method. Values reported are for Day 4 or time-average geometric mean of all values obtained between Day 3 and 14.
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End point type |
Secondary
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End point timeframe |
Plasma samples for measurement of caspofungin concentrations were collected on Day 3 through 14 before dosing and at 1, 2, 4, 8, 12, and 24 hours after initiation of the daily 1-hour infusion.
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| Notes [7] - Participants who received >=1 infusion on Days 3 - 14 and had sufficient plasma concentration data |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with One or More Adverse Events | ||||||||||||
End point description |
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product, is also an adverse experience.
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End point type |
Secondary
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End point timeframe |
Up to 14 days after the last dose of study drug
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Discontinued Due to an Adverse Event | ||||||||||||
End point description |
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product, is also an adverse experience.
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End point type |
Secondary
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End point timeframe |
Up to 14 days after the last dose of study drug
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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 14 days after the last dose of study drug
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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 |
10.0
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Reporting groups
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Reporting group title |
Caspofungin 50 mg/m^2/day
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Reporting group description |
Participants received caspofungin 50 mg/m^2/day in a 1-hour intravenous infusion for a minimum of 4 days and a maximum of 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| None reported | |||
