Clinical Trial Results:
A Phase II, Open Label Trial, to Evaluate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of DRV in Combination With Low-Dose Ritonavir (DRV/Rtv) in Treatment-Experienced HIV-1 Infected Children From 3 Years to Below 6 Years of Age. Week-48 analysis. This trial is referred to as ARIEL.
Due to a system error, the data reported in v1 is not correct and has been removed from public view.
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Summary
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EudraCT number |
2008-004630-25 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
28 Feb 2011
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Jun 2016
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First version publication date |
01 Aug 2015
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Other versions |
v1 (removed from public view) |
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 |
TMC114-TiDP29-C228
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00919854 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Tibotec Pharmaceuticals
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Sponsor organisation address |
Eastgate Village, Eastgate, Little Island, Cork, Ireland,
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Public contact |
Janssen Biologics BV, Janssen-Cilag International NV - Clinical Registry Group, +31 (0)71524 2166, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Janssen Biologics BV, Janssen-Cilag International NV - Clinical Registry Group, +31 (0)71524 2166, ClinicalTrialsEU@its.jnj.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-000038-PIP07-03 | ||
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 |
28 Feb 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Feb 2011
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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 objectives of this study were to evaluate the pharmacokinetic (PK) profile of darunavir (DRV) in combination with low-dose ritonavir (RTV) administered twice daily at steady-state in children aged from 3 to less than (<) 6 years and weighing between 10 and < 20 kilogram (kg) and to support dose recommendation of DRV/rtv to be used in this population by comparing the DRV exposure achieved in these treatment-experienced HIV-1 infected children to that in HIV-1 infected adults and older children weighing more than (>)20 kg. This study also evaluated short-term safety, tolerability, and antiviral activity of DRV/RTV administered twice daily and other ARVs in treatment-experienced children aged from 3 to < 6 years over a 2-week treatment period. In addition, the study also evaluated safety, tolerabiltiy and efficacy of DRV/rtv administered b.i.d. and other ARV agents over a 24-week treatment period at the recommended dose for HIV-1 infected children aged from 3 years to < 6 year
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Protection of trial subjects |
Safety was monitored by means of Data and Safety Monitoring Board (DSMB) analysis. Safety evaluations for this study included the monitoring of adverse events, vital sign measurements, electrocardiogram (ECGs), physical examination, neurological examination and clinical laboratory tests (included biochemistry parameters).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Sep 2009
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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 |
Argentina: 4
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Country: Number of subjects enrolled |
Brazil: 6
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Country: Number of subjects enrolled |
India: 1
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Country: Number of subjects enrolled |
South Africa: 10
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Worldwide total number of subjects |
21
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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) |
0
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Children (2-11 years) |
21
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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 |
27 subjects were recruited and treated in this study; as Good Clinical Practice (GCP) requirements were not consistently adhered to at one site (involving 6 subjects), analyses were performed excluding the subjects from this site, resulting in 21 subjects used for analyses. | ||||||||||
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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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DRV/rtv | ||||||||||
Arm description |
Combination of darunavir and low dose ritonavir administered twice daily. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Darunavir
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Investigational medicinal product code |
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Other name |
TMC114
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Combination of darunavir and low dose ritonavir administered twice daily.
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Investigational medicinal product name |
Ritonavir
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Investigational medicinal product code |
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Other name |
RTV
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Combination of darunavir and low dose ritonavir administered twice daily.
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Baseline characteristics reporting groups
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Reporting group title |
DRV/rtv
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Reporting group description |
Combination of darunavir and low dose ritonavir administered twice daily. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DRV/rtv
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Reporting group description |
Combination of darunavir and low dose ritonavir administered twice daily. | ||
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End point title |
Number of Subjects With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR) [1] | ||||||
End point description |
The TLOVR algorithm was used to derive response, i.e., response and loss of response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered non-responders after discontinuation. Subjects with intermittent missing viral load values were considered responders if the preceding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm. Efficay population included all subjects who received at least 1 dose of study medication.
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End point type |
Primary
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End point timeframe |
Week 24
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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: Descriptive statistics were done, no inferential statistical analyses were performed |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48 - Time to Loss of Virologic Response (TLOVR) | ||||||
End point description |
The TLOVR algorithm was used to derive response, i.e., response and loss of response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered non-responders after discontinuation. Subjects with intermittent missing viral load values were considered responders if the preceding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm. Efficay population included all subjects who received at least 1 dose of study medication.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48 | ||||||||||
End point description |
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered non-responders after discontinuation. Subjects with intermittent missing viral load values were considered responders if the preceding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm. Efficay population included all subjects who received at least 1 dose of study medication.
In addition to the TLOVR analyses, the same sensitivity analyses as for the primary virologic response parameter were performed for plasma viral load < 400 copies/mL: 1) observed case analysis, 2) NC = F analysis, and 3) TLOVR non-VF-censored analysis.
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End point type |
Secondary
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End point timeframe |
Week 24 and Week 48
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48 | ||||||||||
End point description |
The TLOVR algorithm was used to derive response, i.e., response and loss of response needed to be confirmed at 2 consecutive visits and subjects who permanently discontinued were considered non-responders after discontinuation. Subjects with intermittent missing viral load values were considered responders if the preceding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm. Efficay population included all subjects who received at least 1 dose of study medication.
In addition to the TLOVR analyses, the same sensitivity analyses as for the primary virologic response parameter were performed for ≥ 1 log 10 decrease in plasma viral load versus baseline: 1) observed case analysis, 2) NC = F analysis, and 3) TLOVR non-VF-censored analysis.
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End point type |
Secondary
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End point timeframe |
Week 24 and Week 48
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| No statistical analyses for this end point | |||||||||||
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End point title |
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load | ||||||||||||
End point description |
The change in plasma log10 viral load from baseline was calculated using the NC = F algorithm.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24 and Week 48
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage | ||||||||||||
End point description |
CD4+ cell count was calculated using NC = F algorithm
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24 and Week 48
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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 |
48 weeks
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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 |
' 12.1'
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Reporting groups
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Reporting group title |
DRV/rtv
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Reporting group description |
Combination of darunavir and low dose ritonavir administered twice daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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19 May 2009 |
The first amendment included the following changes: 1) updated the protocol text to explain the concept of drug induced liver injury (DILI) and to apply specific toxicity management rules in the presence of DILI; 2) Provided guidance for the testing of hepatitis serology for subjects without documented hepatitis B vaccination; 3) management in case of change in body weight; 4) updated text on storage conditions to ensure consistency with the label text and chagnes to the protocol text were made with regards to pancreatitis; 5) In addtion, changes to the protocol introduction was made as a result of the most recent Investigator Brochure update (Version 10, March 2009). Changes to the protocol text were made regarding management in case of increased lipase/amylase in certain clinical situations; 6) Guidance regarding the backbone is also provided. |
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23 Nov 2009 |
The second amendment included a pharmacokinetic sub-study performed in children participating in trial TMC114-C228. |
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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 | |||
