A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00919854
First received: June 11, 2009
Last updated: November 19, 2013
Last verified: November 2013

June 11, 2009
November 19, 2013
September 2009
August 2010   (final data collection date for primary outcome measure)
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding 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.
To evaluate the pharmacokinetic profile of DRV in combination with low-dose ritonavir [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00919854 on ClinicalTrials.gov Archive Site
  • Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48 [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
  • Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48 [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load [ Time Frame: Baseline, Week 24 and Week 48 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage [ Time Frame: Baseline, Week 24 and Week 48 ] [ Designated as safety issue: No ]
  • To evaluate long-term safety, tolerability and efficacy of DRV/rtv administered b.i.d. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • To evaluate immunology, resistance characteristics, pharmacokinetics, and pharmacokinetic/pharmacodynamic (PK/PD) relationships over 48 weeks of treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
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

The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication), safety and antiviral activity to support dose recommendations by body weight of darunavir with low-dose ritonavir (DRV/rtv), in combination with other antiretroviral drugs (ARVs), in treatment-experienced Human immunodeficiency virus 1 (HIV 1) infected children.

This is an open-label (all people know the identity of the intervention), study to evaluate the pharmacokinetics, safety and antiviral activity. Approximately 24 HIV-1 infected children will be enrolled in this study. The study consists of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Participants will receive DRV/rtv according to their body weight. Safety evaluations will include assessment of adverse events, laboratory tests, physical Examination, neurologic examination, vital signs, and electrocardiogram. The total duration of the study will be 56 weeks.

Interventional
Phase 2
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Human Immunodeficiency Virus 1
  • Drug: Darunavir
    Darunavir oral suspension (100 mg/mL) will be administered as 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg before dose adjustment. Darunavir oral suspension will be administered 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg darunavir tablets twice daily if weight more than or equal to 15 kg after dose adjustment.
  • Drug: Ritonavir
    Ritonavir oral solution (80 mg/mL) will be administered as 3 mg per kg body weight twice daily before dose adjustment and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg.
Experimental: Darunavir (DRV)+Ritonavir (rtv)
Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg.
Interventions:
  • Drug: Darunavir
  • Drug: Ritonavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
February 2011
August 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants with a documented HIV 1 infection (by any of the local standard diagnostic methods, such as HIV PCR-DNA, ELISA or western blot (WB) test for HIV antibodies, etc.)
  • Body weight from 10 kg to less than 20 kg at screening
  • Participants currently on stable ART (anti retroviral therapy) for at least 12 weeks, who need to change their ARV regimen because it is currently failing, with a viral load of greater than 1000 copies/mL
  • Screening genotype resistance test results showing less than 3 DRV resistance-associated mutations
  • Parents or legal representative willing and able to give consent

Exclusion Criteria:

  • Participants with presence of any currently active conditions included in the listing of WHO ( World Health Organisation) Clinical Stage 4 and participants with presence of a non-HIV encephalopathy
  • Administration of any ARV (antiretroviral) or non-ARV investigational medication or investigational vaccine within 30 days prior to screening, except for those medications where dose recommendations for children are available
  • Life expectancy less than 6 months, according to the judgment of the investigator
  • Co-enrollment in other clinical and/or cohort trials without written permission of the Sponsor
  • Participants with any active clinically significant disease (eg, tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study
Both
3 Years to 6 Years
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Brazil,   India,   Kenya,   South Africa
 
NCT00919854
CR012553, TMC114-TiDP29-C228
Yes
Tibotec Pharmaceuticals, Ireland
Tibotec Pharmaceuticals, Ireland
Tibotec Pharmaceutical Limited
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
Tibotec Pharmaceuticals, Ireland
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP