Clinical Trial Results:
Pharmacokinetics and safety of valganciclovir in pediatric heart transplant recipients < 4 months of age.
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Summary
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EudraCT number |
2010-021172-28 |
Trial protocol |
ES |
Global end of trial date |
30 Sep 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jul 2016
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First version publication date |
06 Aug 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 |
NP22523
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01165580 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, CH-4070, Basel, Basel, Switzerland,
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 061 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 061 6878333, global.trial_information@roche.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-000072-PIP01-09 | ||
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 |
30 Jan 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Sep 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2013
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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 |
The primary objective of the study was to characterize the pharmacokinetics of ganciclovir (GCV) following oral administration of valganciclovir (VGCV) in pediatric heart transplant recipients less than (<) 4 months of age.
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Protection of trial subjects |
The investigator ensured that this study was conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 May 2011
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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 |
Spain: 2
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
17
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EEA total number of subjects |
2
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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) |
1
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Infants and toddlers (28 days-23 months) |
16
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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 |
- | ||||||||||
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Pre-assignment
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Screening details |
Participants who were heart transplant recipients, aged < 4 months (<125 days), considered hemodynamically stable, at risk of cytomegalovirus (CMV) disease and are being treated with intravenous GCV or VGCV oral solution for the prevention of CMV disease. | ||||||||||
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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 |
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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VGCV: All treated participants | ||||||||||
Arm description |
Participants aged < 4 months received 2 doses (one dose per day on 2 consecutive days) of VGCV orally according to the following dosing algorithm: Dose of VGCV is equal to 7 times the multiplied value of the subject's body surface area (BSA) and creatinine clearance estimated by modified Schwartz formula (CrCLS) in milligrams (mg). If the calculated dose was greater than (>) 900 mg then dose given was 900 mg. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Valganciclovir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 2 doses of VGCV orally (one dose per day) according to the following dosing algorithm. Dose of VGCV is equal to 7 times the multiplied value of the subject's BSA and CrCLS. If the calculated dose was >900 mg then dose given was 900 mg.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
VGCV: All treated participants
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Reporting group description |
Participants aged < 4 months received 2 doses (one dose per day on 2 consecutive days) of VGCV orally according to the following dosing algorithm: Dose of VGCV is equal to 7 times the multiplied value of the subject's body surface area (BSA) and creatinine clearance estimated by modified Schwartz formula (CrCLS) in milligrams (mg). If the calculated dose was greater than (>) 900 mg then dose given was 900 mg. | ||
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End point title |
Area Under the Concentration-Time Curve Over the Dosing Interval (AUC 0-24 hours) for GCV [1] | ||||||||
End point description |
An integrated population pharmacokinetics (PopPK) model was used to characterize the pharmacokinetics (PK) of GCV which combined the results of this study in pediatric heart transplant participants along with other 3 studies (WP16296, WP16303 and WV16726). The PopPK model is a 2-compartment PK model with first order formation following administration of VGCV with a lag time.
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End point type |
Primary
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End point timeframe |
On study Days 2 and 3: pre-dose, 1-3 hours, 3-7 hours, 7-12 hours and 24 hours post-dose.
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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 statistical analysis was performed as this was not part of the planned primary endpoint analysis. |
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| Notes [2] - PopPK analysis was performed in the initial 14 participants, not all treated participants. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Volume of Distribution of GCV [3] | ||||||||||||
End point description |
PopPK model was used to characterize the PK of GCV which combined the results of this study in pediatric heart transplant participants along with other 3 studies (WP16296, WP16303 and WV16726). The PopPK model is a 2-compartment PK model with first order formation following administration of VGCV with a lag time.
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End point type |
Primary
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End point timeframe |
On study days 2 and 3: pre-dose, 1-3 hours, 3-7 hours, 7-12 hours and 24 hours post-dose.
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| Notes [3] - 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 statistical analysis was performed as this was not part of the planned primary endpoint analysis. |
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| Notes [4] - PopPK analysis was performed in the initial 14 participants, not all treated participants. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Terminal Half-life of GCV [5] | ||||||||
End point description |
PopPK model was used to characterize the PK of GCV which combined the results of this study in pediatric heart transplant participants along with other 3 studies (WP16296, WP16303 and WV16726). The PopPK model is a 2-compartment PK model with first order formation following administration of VGCV with a lag time.
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End point type |
Primary
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End point timeframe |
On study days 2 and 3: pre-dose, 1-3 hours, 3-7 hours, 7-12 hours and 24 hours post-dose.
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| Notes [5] - 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 statistical analysis was performed as this was not part of the planned primary endpoint analysis. |
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| Notes [6] - PopPK analysis was performed in the initial 14 participants, not all treated participants. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Concentration (Cmax) of GCV [7] | ||||||||
End point description |
PopPK model was used to characterize the PK of GCV which combined the results of this study in pediatric heart transplant participants along with other 3 studies (WP16296, WP16303 and WV16726). The PopPK model is a 2-compartment PK model with first order formation following administration of VGCV with a lag time.
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End point type |
Primary
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End point timeframe |
On study days 2 and 3: pre-dose, 1-3 hours, 3-7 hours, 7-12 hours and 24 hours post-dose.
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| Notes [7] - 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 statistical analysis was performed as this was not part of the planned primary endpoint analysis. |
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| Notes [8] - PopPK analysis was performed in the initial 14 participants, not all treated participants. |
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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 |
AEs were assessed throughout the study period up to 7 (+/-2) days, post 2nd VGCV dose.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
VGCV: All treated participants
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Reporting group description |
Participants aged < 4 months received 2 doses (one dose per day on 2 consecutive days) of VGCV POS according to dosing using the dosing algorithm: Dose of VGCV = 7 * BSA * CrCLS. If the calculated dose was >900 mg then dose given was 900 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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30 Sep 2010 |
This protocol amendment documented that two doses would be received, added a 24-hour PK sample collection, specified a 5-part differential cell count, added an upper limit to the CrCL, updated and specified route of administration, updated the adverse event intensity to a 3-point scale, updated serious adverse event reporting requirements, and added an interim analysis to be performed after four participants have been enrolled in the birth to < 6 weeks age group to assess the effectiveness of the dosing algorithm in this age group. |
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30 Mar 2012 |
This protocol amendment documented that dosing would not be automatically calculated on the electronic case report form (eCRF), added a window for the post-dosing assessment timeframe, specified when to start collecting previous/concurrent diseases and treatments in the screening assessments, clarified the supplies that would be provided for the administration of the Investigational Medicinal Product (IMP), and modified the inclusion criteria to state participants had to be < 125 days at the time of the last PK assessment and participants with any form of tube feeding can be included. |
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28 Dec 2012 |
This protocol amendment provided clarification regarding enrollment of 16 participants in the study but recruitment has not been met in the age group birth to < 6 weeks changed the participant numbers to permit a minimum of 16 and a maximum of 24 participants to be enrolled into the study. A maximum recruitment number (24 participants) was provided, allowing for a minimum of four, and maximum of eight participants in the birth to < 6 weeks of age group. The total number of participants to be enrolled in this younger group is dependent on results from ongoing PK data analysis, and whether the data are consistent (within agreed variability boundaries) with those observed in participants at least 4 months of age. The planned recruitment period has been extended to approximately 3 years to allow sufficient time to recruit the required number of participants within the birth to < 6 weeks of age group to facilitate dosing recommendations in this age group. |
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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 | |||
