A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents (DIONE)
The purpose of this study is to evaluate pharmacokinetics (what body does to medication), safety, tolerability, and efficacy (effectiveness) of darunavir with low-dose ritonavir (DRV/rtv) administered once daily, in combination with an investigator-selected background regimen consisting of other antiretrovirals (ARVs) ie, 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in treatment-naive (never treated before) HIV-1 infected adolescents aged from 12 to <18 years and weighing at least 40 kg.
|Study Design:||Allocation: Non-Randomized
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/Rtv Once Daily in Treatment-Naive HIV-1 Infected Adolescents Aged Between 12 and < 18 Years|
- Virological Response[Viral Load <50 Copies/mL, TLOVR] [ Time Frame: Week 24 ] [ Designated as safety issue: No ]The analysis is based on virologic response defined as percentage of patients with confirmed plasma viral load <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.
- Virological Response [Viral Load <50 Copies/mL, FDA-SNAPSHOT] [ Time Frame: Week 24 ] [ Designated as safety issue: No ]The analysis is based on the last observed viral load (VL) data within the Week 24 window. Virologic response is defined as a VL<50 copies/mL (observed case). Virologic Failure includes a) patients who had >=50 copies/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).
|Study Start Date:||July 2009|
|Study Completion Date:||March 2011|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Experimental: DRV/rtv (darunavir/ritonavir)
Patients will receive darunavir tablets 2 x 400 mg in combination with ritonavir capsule 100 mg once daily for 48 weeks along with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) ie, either zidovudine/lamivudine or abacavir/lamivudine
Type=exact number, unit=mg, number=400, formulation=tablet, route=oral. 2 tablets of darunavir administered once daily for 48 weeks
Other Name: DRVDrug: ritonavir
Type=exact number, unit=mg, number=100, formulation=capsule, route=oral. 1 capsule of ritonavir administered once daily for 48 weeks
Other Name: rtvDrug: zidovudine
NRTI (zidovudine) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country
Other Name: zidovudineDrug: lamivudine
NRTI (lamivudine) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country
Other Name: lamivudineDrug: abacavir
NRTI (abacavir) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country
Other Name: abacavir
This is an open-label (all people know the identity of the intervention), single-arm, Phase II study to evaluate the pharmacokinetics, safety, tolerability, and efficacy of darunavir/ritonavir (DRV/rtv) administered once daily, in combination an investigator-selected background regimen (2 NRTIs), in treatment-naive HIV-1 infected adolescents over 48 weeks. A total of 12 patients will be enrolled in this study. Patients will be considered treatment-naive if they have never received treatment with an ARV medication, including both investigational as well as commercially available ARVs indicated for the treatment of HIV-infection and ARVs for the treatment of hepatitis B infection with anti-HIV activity. The investigator-selected background regimen will consist of 2 NRTIs, either zidovudine/lamivudine or abacavir/lamivudine, whichever is approved and marketed or considered local standard of care for adolescents aged from 12 to <18 years in a particular country. The study will consist of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Safety, efficacy, resistance (reduction in effectiveness of a medication), pharmacokinetic analyses, and pharmacodynamic (what medication does to body) analyses will be performed at Week 24 (primary analysis) and Week 48 (final analysis). Patients who will complete the 48 weeks of treatment with DRV/rtv and who will continue to benefit from this treatment, will have the opportunity to continue this treatment until they no longer benefit from the medication, until DRV is commercially available or can be accessed from another source (eg, access program, government program) or until the development program is discontinued.
|United States, Tennessee|
|Memphis, Tennessee, United States|
|Esplugues De Llobregat, Spain|
|Birmingham, United Kingdom|
|Bristol, United Kingdom|
|Stoke On Trent, United Kingdom|
|Study Director:||Tibotec Pharmaceuticals Clinical Trial||Tibotec Pharmaceutical Limited|