Clinical Trial Results:
Once daily DArunavir/ritonavir in HIV-infected children 6-12 years old: a PHarmacokiNEtic validation of model-based dosing recommendations (DAPHNE)
Summary
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EudraCT number |
2014-001111-39 |
Trial protocol |
NL |
Global end of trial date |
19 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Sep 2019
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First version publication date |
21 Sep 2019
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Other versions |
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Summary report(s) |
DAPHNE paper |
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 |
UMCN-AKF13.03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands,
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Public contact |
David Burger, Radboud University Medical Center, david.burger@radboudumc.nl
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Scientific contact |
David Burger, Radboud University Medical Center, david.burger@radboudumc.nl
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Apr 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jul 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Jul 2017
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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 |
To validate FDA-approved dosing recommendation for once daily DRV/r in children 6-12 years old. This will be done by evaluating the pharmacokinetics of DRV/r given once daily (according to FDA dosing guideline) to children from 6 – 12 years
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Protection of trial subjects |
The risk-classification is assessed as negligible to the patient population receiving study drug at the current regimens. The drug (darunavir) is licensed by the FDA for the use as investigated in this protocol. A rich sampling pharmacokinetic assessment, performed after switch to a once-daily regime, is part of current routine clinical practice for children who are treated with a antiretroviral drugs.
There are no real risks involved. Anaemia because of PK sampling is unlikely, because the amount of blood that will be taken solely for study purposes is within the limits of international standards.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2014
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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 |
Netherlands: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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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) |
0
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Children (2-11 years) |
12
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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 |
Twelve children were enrolled from four sites in the Netherlands. | ||||||||||
Pre-assignment
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Screening details |
Children (6–12 years of age) were eligible when they used darunavir/ritonavir once-daily for at least 2 weeks according to the approved dose. | ||||||||||
Period 1
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Period 1 title |
screening
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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DRV/rtv QD | ||||||||||
Arm description |
In this multicenter pharmacokinetic study in HIV-infected children (6–12 years of age), we validated the approved once-daily darunavir/ritonavir dosing recommendations. | ||||||||||
Arm type |
Active comparator | ||||||||||
Investigational medicinal product name |
darunavir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
≥ 15 kg to < 30 kg DRV 600 mg with ritonavir 100 mg
≥ 30 kg to < 40 kg DRV 675 mg with ritonavir 100 mg
≥ 40 kg DRV 800 mg with ritonavir 100 mg
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Period 2
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Period 2 title |
PK sampling DRV/rtv QD
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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DRV/rtv QD | ||||||||||
Arm description |
Children were using DRV/rtv QD treatment dosed according to EMA approved SPC. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
darunavir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
≥ 15 kg to < 30 kg DRV 600 mg with ritonavir 100 mg
≥ 30 kg to < 40 kg DRV 675 mg with ritonavir 100 mg
≥ 40 kg DRV 800 mg with ritonavir 100 mg
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Period 3
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Period 3 title |
adult data
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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daruanvir adult | ||||||||||
Arm description |
this is information from literature, therefore number of subjects is put in as 1 (start 12, as otherwise we get errors). | ||||||||||
Arm type |
Active comparator | ||||||||||
Investigational medicinal product name |
darunavir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
DRV 800 mg with ritonavir 100 mg, adult dose
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Baseline characteristics reporting groups
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Reporting group title |
screening
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DRV/rtv QD
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Reporting group description |
In this multicenter pharmacokinetic study in HIV-infected children (6–12 years of age), we validated the approved once-daily darunavir/ritonavir dosing recommendations. | ||
Reporting group title |
DRV/rtv QD
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Reporting group description |
Children were using DRV/rtv QD treatment dosed according to EMA approved SPC. | ||
Reporting group title |
daruanvir adult
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Reporting group description |
this is information from literature, therefore number of subjects is put in as 1 (start 12, as otherwise we get errors). | ||
Subject analysis set title |
DAPHNE
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All patients in the study
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End point title |
AUC0-24 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
one day
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Notes [1] - literature data |
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Statistical analysis title |
descriptive | ||||||||||||
Statistical analysis description |
comparison of AUC values in children to adults.
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Comparison groups |
DRV/rtv QD v daruanvir adult
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Number of subjects included in analysis |
13
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | ||||||||||||
P-value |
< 0.05 [3] | ||||||||||||
Method |
t-test, 1-sided | ||||||||||||
Parameter type |
none | ||||||||||||
Confidence interval |
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Notes [2] - comparison of AUC values in children to adults. [3] - not applicable |
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Adverse events information
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Timeframe for reporting adverse events |
entire study
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Assessment type |
Non-systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
none | ||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
DAPHNE
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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. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/29474261 |