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

NCT00919854 | Completed Phase 2 Results DMC

• 2 other identifiers: CR012553TMC114-TiDP29-C228
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 8

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.

Conditions

Human Immunodeficiency Virus 1

Keywords

Human immunodeficiency virus 1; HIV-1; Darunavir; Ritonavir; Norvir

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 24

Secondary Outcomes (5)

• Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48

  Week 48

• Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48

  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

  Week 24 and Week 48

• Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load

  Baseline, Week 24 and Week 48

• Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage

  Baseline, Week 24 and Week 48

Study Arms (1)

Darunavir (DRV)+Ritonavir (rtv)

EXPERIMENTAL

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; Drug: Ritonavir

Interventions

Darunavir DRUG

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.

Darunavir (DRV)+Ritonavir (rtv)

Ritonavir DRUG

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.

Darunavir (DRV)+Ritonavir (rtv)

Eligibility Criteria

• Age: 3 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead
• Tibotec Pharmaceutical Limited: collaborator

Study Sites (8)

Unknown Facility

Buenos Aires, Argentina

Location

Unknown Facility

Rio de Janeiro, Brazil

Location

Unknown Facility

São Paulo, Brazil

Location

Unknown Facility

Chennai, India

Location

Unknown Facility

Kilifi, Kenya

Location

Unknown Facility

Durban, South Africa

Location

Unknown Facility

Johannesburg, South Africa

Location

Unknown Facility

Johannesburg Gauteng, South Africa

Location

Related Publications (1)

• 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.

  PMID: 25719453 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Darunavir; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Results Point of Contact

• Title: Senior Director R&D
• Organization: Janssen R&D US

1 609 730-7548

Study Officials

• Tibotec Pharmaceuticals, Ireland Clinical Trial

  Tibotec Pharmaceuticals, Ireland

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2009
• First Posted: June 12, 2009
• Study Start: September 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: February 1, 2011
• Last Updated: April 23, 2014
• Results First Posted: June 24, 2013

Record last verified: 2014-04

Locations

AR (1); KE (1); ZA (3); IN (1); BR (2)