Back to resultsA Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents (DIONE)
Primary Purpose
HIV-1 Infection
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
darunavir
ritonavir
zidovudine
lamivudine
abacavir
Sponsored by
About this trial
This is an interventional treatment trial for HIV-1 Infection focused on measuring HIV Infections, TMC114-TiDP29-C230, TMC114-C230, TMC114, HIV-1, Darunavir, Ritonavir, NRTI, Treatment Naive
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DRV/rtv (darunavir/ritonavir)
Arm Description
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
Outcomes
Primary Outcome Measures
Virological Response[Viral Load <50 Copies/mL, TLOVR]
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]
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).
Full Information
NCT ID
NCT00915655
First Posted
June 4, 2009
Last Updated
August 28, 2012
Sponsor
Tibotec Pharmaceuticals, Ireland
Collaborators
Tibotec Pharmaceutical Limited
1. Study Identification
Unique Protocol Identification Number
NCT00915655
Brief Title
A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents
Acronym
DIONE
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
March 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 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection
Keywords
HIV Infections, TMC114-TiDP29-C230, TMC114-C230, TMC114, HIV-1, Darunavir, Ritonavir, NRTI, Treatment Naive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DRV/rtv (darunavir/ritonavir)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
darunavir
Other Intervention Name(s)
DRV
Intervention Description
Type=exact number, unit=mg, number=400, formulation=tablet, route=oral. 2 tablets of darunavir administered once daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
ritonavir
Other Intervention Name(s)
rtv
Intervention Description
Type=exact number, unit=mg, number=100, formulation=capsule, route=oral. 1 capsule of ritonavir administered once daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
zidovudine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
lamivudine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
abacavir
Intervention Description
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
Primary Outcome Measure Information:
Title
Virological Response[Viral Load <50 Copies/mL, TLOVR]
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Virological Response [Viral Load <50 Copies/mL, FDA-SNAPSHOT]
Description
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).
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tibotec Pharmaceuticals Clinical Trial
Organizational Affiliation
Tibotec Pharmaceutical Limited
Official's Role
Study Director
Facility Information:
City
Memphis
State/Province
Tennessee
Country
United States
City
Paris
Country
France
City
Dublin
Country
Ireland
City
Esplugues De Llobregat
Country
Spain
City
Madrid
Country
Spain
City
Kiev
Country
Ukraine
City
Birmingham
Country
United Kingdom
City
Bristol
Country
United Kingdom
City
Stoke On Trent
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents
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