Clinical Trial Results:
Pharmacokinetics of posaconazole (Noxafil(R)) as prophylaxis for invasive fungal disease
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Summary
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EudraCT number |
2016-001182-87 |
Trial protocol |
NL BE |
Global end of trial date |
09 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Mar 2020
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First version publication date |
19 Mar 2020
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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 |
UMCN-AKF16.01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands, 6525 GA
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Public contact |
Roger Brüggemann, Radboud University Medical Centre, +31 243616405, roger.bruggemann@radboudumc.nl
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Scientific contact |
Roger Brüggemann, Radboud University Medical Centre, +31 243616405, r.bruggemann@akf.umcn.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 |
03 Feb 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Feb 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Feb 2019
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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 determine the pharmacokinetics of posaconazole (new solid oral and IV) given as prophylaxis to patients who are at risk for developing fungal infections after receiving immunosuppressive therapy for acute GVHD, (non)myeloablative or reduced intensity conditioning regimens for SCT, or remission induction chemotherapy for AML/MDS.
• To determine the oral bioavailability and specific the impact of mucositis on changes in drug absorption or presystemic clearance.
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Protection of trial subjects |
This study uses posaconazole, which is an antifungal agent licensed for prophylaxis as well treatment of invasive fungal infections. The dosages and clinical indications used in this trial are similar to the licensed dosages or lower; therefore no potential harmful risks are expected in this cohort. Furthermore, the study medication, posaconazole, given as antifungal prophylaxis is given on top of standard intensive diagnostic work-up to detect a fungal infection as soon as possible.
The burden of the patient is identical to studies previously performed in the same cohort (voriconazole, anidulafungin and micafungin, all approved by the ethics committee). We strongly believe the burden for the patient as well as the risk for severe adverse events is reduced to an absolute minimum.
The risk-classification is assessed as negligible to the patient population receiving study drug at the current regimens. The drug is licensed for the use investigated in this protocol. Safety data on the use of higher dose are published and very-well defined. There is no attributable risk for the application of the study protocol to the haematology patients at risk for fungal infections.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2016
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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: 15
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Country: Number of subjects enrolled |
Belgium: 12
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Worldwide total number of subjects |
27
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EEA total number of subjects |
27
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
17
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment took place from August 2016 to 08-06-2019 in Nijmegen, Netherlands and Leuven in Belgium. | |||||||||
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Pre-assignment
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Screening details |
Patient receives immunosuppressive therapy for acute GVHD grade II-IV, reduced intensity conditioning regimens for allogeneic stem cell transplant, or first remission induction chemotherapy for AML/MDS. In case of acute GVHD grade II-IV, patient has received less than 1 week of immunosuppressive therapy. ASAT <200U/L, ALAT <225U/L, AP <460U/L | |||||||||
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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 | |||||||||
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Arms
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Arm title
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all patients | |||||||||
Arm description |
- | |||||||||
Arm type |
none | |||||||||
Investigational medicinal product name |
posaconazole not yet started
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
no dose administered at screening
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Period 2
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Period 2 title |
Treatment
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Is this the baseline period? |
No | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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posa ref | |||||||||
Arm description |
posaconazole iv treatment | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
posaconazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
posaconazole IV 300mg BID on the first day (posaconazole will be infused over a period of 90 minutes), days 2-7 patients will receive posaconazole IV 300mg QD.
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Arm title
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posa oral | |||||||||
Arm description |
posaconazol oral | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
posaconazole oral
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
posaconazole PO 300mg BID on the first day, days 2-7: patients will receive posaconazole PO 300mg QD.
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Baseline characteristics reporting groups
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Reporting group title |
screening
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Reporting group description |
screened patients | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
all subjects
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
subjects for demographics
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End points reporting groups
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Reporting group title |
all patients
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Reporting group description |
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Reporting group title |
posa ref
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Reporting group description |
posaconazole iv treatment | ||
Reporting group title |
posa oral
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Reporting group description |
posaconazol oral | ||
Subject analysis set title |
all subjects
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
subjects for demographics
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End point title |
posa AUC0-24h [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
24hour after observed dosing
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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: no formal analysis was done |
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| Notes [2] - should be 17, as intrasubject |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
entire study
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Adverse event reporting additional description |
SAE
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||
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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 |
all subjects
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: no non-serious AEs were reported |
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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 | |||
