Clinical Trial Results:
A phase II, open-label trial, to evaluate pharmacokinetics, safety, tolerability and antiviral activity of DRV/rtv once daily in treatment-naïve HIV-1 infected adolescents aged between 12 and < 18 years. Week-48 Final analysis. This trial is referred to as DIONE.
Summary
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EudraCT number |
2008-004631-37 |
Trial protocol |
IE GB FR ES IT Outside EU/EEA |
Global end of trial date |
31 Mar 2011
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Results information
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Results version number |
v1 |
This version publication date |
06 Jul 2016
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First version publication date |
29 Jul 2015
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Other versions |
v2 |
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-C230
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00915655 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Tibotec Pharmaceuticals
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Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, 2340
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Public contact |
Clinical Registry Group, Tibotec Pharmaceuticals Ltd, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Tibotec Pharmaceuticals Ltd, 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-PIP01-07 | ||
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 |
31 Mar 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 |
31 Mar 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 objective of this study was to evaluate the pharmacokinetics, safety, tolerability, and efficacy of darunavir with low-dose ritonavir (DRV/rtv) administered at 800/100 mg once daily (q.d.) in
combination with an investigator-selected background regimen, consisting of either zidovudine (AZT)/lamivudine (3TC) or abacavir (ABC)/3TC, over a 24-week treatment period in antiretroviral (ARV) treatment-naïve HIV-1 infected adolescents aged between 12 and < 18 years and weighing ≥ 40 kg.
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Protection of trial subjects |
Safety and tolerability of subjects were evaluated by monitoring of the incidence and type of adverse events (AEs)/ HIV-Related Events, performing Clinical Laboratory Tests ( Hematology and Coagulation, Biochemistry, Urinalysis, Hepatitis Serology/Viremia) , Cardiovascular Safety tests (Electrocardiogram, Vital Signs) and other safety evaluations including Physical examination and Pubertal Development - Tanner Stage throughout the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Aug 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 |
Spain: 1
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Ukraine: 6
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Country: Number of subjects enrolled |
United States: 2
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Worldwide total number of subjects |
12
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EEA total number of subjects |
4
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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) |
12
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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 was conducted from 21-Aug-2009 to 31-March-2011 and subjects from 6 countries were enrolled. | ||||||
Pre-assignment
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Screening details |
In total 12 subjectss were screened, and all 12 subjects were treated and completed the entire study. | ||||||
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 | ||||||
Arms
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Arm title
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DRV/rtv 800/100 mg q.d. | ||||||
Arm description |
Subjects were administered with Darunavir in combination with low-dose of ritonavir (DRV/rtv) at 800/100 mg once daily (q.d.) in combination with an investigator-selected background regimen, consisting of either zidovudine (AZT)/lamivudine (3TC) or abacavir (ABC)/3TC. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Darunavir
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Investigational medicinal product code |
TMC114
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Other name |
Prezista
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects were administered with two Darunavir 400 milligrams (mg) film coated tablets (2x400mg=800mg) orally once in a day.
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Investigational medicinal product name |
Ritonavir
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Investigational medicinal product code |
RTV
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Other name |
Norvir
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects were administered with Ritonavir 100 milligrams (mg) capsule orally once in a day.
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Baseline characteristics reporting groups
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Reporting group title |
DRV/rtv 800/100 mg q.d.
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Reporting group description |
Subjects were administered with Darunavir in combination with low-dose of ritonavir (DRV/rtv) at 800/100 mg once daily (q.d.) in combination with an investigator-selected background regimen, consisting of either zidovudine (AZT)/lamivudine (3TC) or abacavir (ABC)/3TC. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DRV/rtv 800/100 mg q.d.
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Reporting group description |
Subjects were administered with Darunavir in combination with low-dose of ritonavir (DRV/rtv) at 800/100 mg once daily (q.d.) in combination with an investigator-selected background regimen, consisting of either zidovudine (AZT)/lamivudine (3TC) or abacavir (ABC)/3TC. |
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End point title |
Virological Response[Viral Load <50 Copies/mL, (Time to Loss of Virologic Response) TLOVR] [1] | ||||||||||
End point description |
The analysis is based on virologic response defined as percentage of patients with confirmed plasma viral load less than (<) 50 HIV-1 RNA copies/mL at Week 24 calculated according to the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) algorithm.
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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: Inferential statistical analyses were not performed as this is a single arm study |
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No statistical analyses for this end point |
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End point title |
Virological Response [Viral Load <50 Copies/mL, FDA-SNAPSHOT] | ||||||
End point description |
The analysis is based on the last observed viral load (VL) data within the Week 24 window. Virologic response is defined as a VL less than (<) 50 copies/mL (observed case). Virologic Failure includes a) patients who had greater than or equal to (>=) 50 copies/millilitre (mL) in the Week 24 window, b) patients who discontinued prior to Week 24 for lack or loss of efficacy, c) patients who had a switch in their background regimen that was not permitted by the protocol, and d) patients who discontinued for reasons other than adverse events (AEs)/death, and lack or loss of efficacy (provided their last available viral load was detectable).
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End point type |
Secondary
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End point timeframe |
Week 24
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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 |
Baseline upto week 52.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 800/100 mg q.d.
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Reporting group description |
darunavir with low-dose ritonavir (DRV/rtv) administered at 800/100 mg once daily (q.d.) in combination with an investigator-selected background regimen, consisting of either zidovudine (AZT)/lamivudine (3TC) or abacavir (ABC)/3TC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |