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: April 3, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Human Immunodeficiency Virus 1
Drug: Darunavir
Drug: Ritonavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

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) [ 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 27
Study Start Date: September 2009
Study Completion Date: February 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   3 Years to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00919854

Locations
Argentina
Buenos Aires, Argentina
Brazil
Rio De Janeiro, Brazil
Sao Paulo, Brazil
India
Chennai, India
Kenya
Kilifi, Kenya
South Africa
Durban, South Africa
Johannesburg, South Africa
Johannesburg Gauteng, South Africa
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Tibotec Pharmaceutical Limited
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00919854     History of Changes
Other Study ID Numbers: CR012553, TMC114-TiDP29-C228
Study First Received: June 11, 2009
Results First Received: August 3, 2011
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Human immunodeficiency virus 1
HIV-1
Darunavir
Ritonavir
Norvir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Antiviral Agents
Ritonavir
Darunavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on August 19, 2014