A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV-1 Infection	Drug: darunavir Drug: ritonavir Drug: zidovudine Drug: lamivudine Drug: abacavir	Phase 2


Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Lamivudine Abacavir Ritonavir Abacavir sulfate Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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).


Enrollment:	12
Study Start Date:	July 2009
Study Completion Date:	March 2011
Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	Drug: darunavir Type=exact number, unit=mg, number=400, formulation=tablet, route=oral. 2 tablets of darunavir administered once daily for 48 weeks Other Name: DRV Drug: ritonavir Type=exact number, unit=mg, number=100, formulation=capsule, route=oral. 1 capsule of ritonavir administered once daily for 48 weeks Other Name: rtv Drug: 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 Drug: 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 Drug: 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

Arms

Assigned Interventions

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

Drug: darunavir

Type=exact number, unit=mg, number=400, formulation=tablet, route=oral. 2 tablets of darunavir administered once daily for 48 weeks

Other Name: DRV

Drug: ritonavir

Type=exact number, unit=mg, number=100, formulation=capsule, route=oral. 1 capsule of ritonavir administered once daily for 48 weeks

Other Name: rtv

Drug: 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

Drug: 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

Drug: 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

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	12 Years to 18 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with a documented HIV-1 infection
Body weight from at least 40 kg at screening
Screening plasma HIV-1 RNA >= 1000 copies/mL
Parents or legal representative and trial patients (where appropriate, depending on age and local regulation) willing and able to give consent and assent
General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial
Able to swallow darunavir tablets (400 mg) and ritonavir capsules (100 mg)

Exclusion Criteria:

Patients with presence of any currently active conditions included in the listing of World Health Organisation (WHO) Clinical Stage 4
Any condition (including, but not limited to, alcohol and drug use), which, in the opinion of the investigator, could compromise the patient's safety or adherence to the trial protocol
Previous or current use of antiretrovirals (ARVs)
Primary or acute HIV infection
Use of any investigational agents within 30 days prior to screening
Use of disallowed concomitant therapy
Pregnant or breast-feeding
Female patient of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period
Patients with clinical or laboratory evidence of significantly decreased hepatic function or decompensation (ie, liver insufficiency), irrespective of liver enzyme levels
Any active clinically significant disease (eg, cardiac dysfunction, pancreatitis, acute viral infection) or findings during screening of medical history or physical examination that are expected to compromise the patient's safety or outcome in the trial

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: NCT00915655

Locations


United States, Tennessee

Memphis, Tennessee, United States
France

Paris, France
Ireland

Dublin, Ireland
Spain

Esplugues De Llobregat, Spain

Madrid, Spain
Ukraine

Kiev, Ukraine
United Kingdom

Birmingham, United Kingdom

Bristol, United Kingdom

Stoke On Trent, United Kingdom

Sponsors and Collaborators

Tibotec Pharmaceuticals, Ireland

Tibotec Pharmaceutical Limited

Investigators


Study Director:	Tibotec Pharmaceuticals Clinical Trial	Tibotec Pharmaceutical Limited

More Information


Responsible Party:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00915655 History of Changes
Other Study ID Numbers:	CR016312 TMC114-TiDP29-C230 2008-004631-37
Study First Received:	June 4, 2009
Results First Received:	November 25, 2011
Last Updated:	August 28, 2012
Health Authority:	United States: Food and Drug Administration Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:


HIV Infections TMC114-TiDP29-C230 TMC114-C230 TMC114 HIV-1	Darunavir Ritonavir NRTI Treatment Naive

Additional relevant MeSH terms:


Ritonavir Darunavir Lamivudine Zidovudine Abacavir Antiviral Agents HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors	Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Antimetabolites

ClinicalTrials.gov processed this record on September 29, 2016

A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents (DIONE)