Back to resultsA Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
Primary Purpose
Human Immunodeficiency Virus 1
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Darunavir
Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus 1 focused on measuring Human immunodeficiency virus 1, HIV-1, Darunavir, Ritonavir, Norvir
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Darunavir (DRV)+Ritonavir (rtv)
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
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.
Secondary Outcome Measures
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Full Information
NCT ID
NCT00919854
First Posted
June 11, 2009
Last Updated
April 3, 2014
Sponsor
Tibotec Pharmaceuticals, Ireland
Collaborators
Tibotec Pharmaceutical Limited
1. Study Identification
Unique Protocol Identification Number
NCT00919854
Brief Title
A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tibotec Pharmaceuticals, Ireland
Collaborators
Tibotec Pharmaceutical Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus 1
Keywords
Human immunodeficiency virus 1, HIV-1, Darunavir, Ritonavir, Norvir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Darunavir (DRV)+Ritonavir (rtv)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Darunavir
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
Time Frame
Week 48
Title
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
Title
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
Title
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Time Frame
Baseline, Week 24 and Week 48
Title
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Time Frame
Baseline, Week 24 and Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tibotec Pharmaceuticals, Ireland Clinical Trial
Organizational Affiliation
Tibotec Pharmaceuticals, Ireland
Official's Role
Study Director
Facility Information:
City
Buenos Aires
Country
Argentina
City
Rio De Janeiro
Country
Brazil
City
Sao Paulo
Country
Brazil
City
Chennai
Country
India
City
Kilifi
Country
Kenya
City
Durban
Country
South Africa
City
Johannesburg Gauteng
Country
South Africa
City
Johannesburg
Country
South Africa
12. IPD Sharing Statement
Citations:
PubMed Identifier
25719453
Citation
Violari A, Bologna R, Kumarasamy N, Pilotto JH, Hendrickx A, Kakuda TN, Lathouwers E, Opsomer M, Van de Casteele T, Tomaka FL. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial. Pediatr Infect Dis J. 2015 May;34(5):e132-7. doi: 10.1097/INF.0000000000000644.
Results Reference
derived
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A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
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