Back to resultsA Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN) (ODIN)
Primary Purpose
Human Immunodeficiency Virus - Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Darunavir (DRV)
Ritonavir (rtv)
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus - Type 1 focused on measuring Human immunodeficiency virus - type 1, HIV-1 Infection, TMC-114, Darunavir, Ritonavir
Eligibility Criteria
Inclusion Criteria:
- Patients with documented human immunodeficiency virus - Type 1 (HIV-1) infection
- Patients with a viral load greater than 1,000 HIV-1 ribonucleic acid (RNA) copies/mL
- Stable highly active antiretroviral therapy (HAART) regimen for at least 12 weeks at screening
- In the investigator's opinion, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not a valid treatment option, because of the patient's antiretroviral (ARV) treatment history, ARV resistance testing, medication-taking behavior, safety and tolerability concerns, or other patient-related factors
- Prescreening or/and screening plasma HIV-1 RNA greater than 1,000 copies/mL on HAART regimen at screening
Exclusion Criteria:
- Presence of any currently active conditions that fit the definition of the World Health Organization (WHO) Clinical Stage 4, with the following exceptions: stable cutaneous kaposi's sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study time period, wasting syndrome
- Patients for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine
- Previous or current use of enfuvirtide (ENF), tipranavir and/or DRV
- Life expectancy of less than 12 months
- Pregnant or breast-feeding females
- 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 patient's safety or outcome of the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
DRV/rtv 800/100 mg once daily
DRV/rtv 600/100 mg twice daily
Arm Description
Two 400 mg darunavir (DRV) ie, TMC114 tablets + one 100 mg ritonavir (rtv) capsule once daily.
One 600 mg TMC114 tablet + one 100 mg capsule of rtv twice daily.
Outcomes
Primary Outcome Measures
Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
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
Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)
Number of participants with confirmed plasma viral load less than 400 copies/mL at Week 48.
Change in log10 Viral Load From Baseline at Week 48
Time to Reach First Virologic Response
Time (in weeks) to achieve viral load less than 50 copies/mL by the participants.
Time to Loss of Virologic Response
Time taken to lose the virologic response ie, plasma viral load less than 50 copies/mL by participants.
Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks
Change in CD4+ Cell Count From Baseline
CD4+ cell count was calculated using the Last Observation Carried Forward (LOCF) algorithm.
Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
The FAHI is a 44-item questionnaire and incorporates 5 functional scales (physical well-being, emotional well-being/living with HIV, functional and global well-being, social well-being, and cognitive functioning). Each scale included several questions (all 5 scales include total 44 questions). For each question, participants gave a score of either 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). Total FAHI imputed score is calculated by adding scores for each question. The range of total FAHI score is 0 to 176. Higher scores indicate worsening.
Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48
Self-reported adherence to the ARV medications was measured. The M-MASRI asks participants to report the number of doses taken, as well as the number of doses taken during the last 30 days prior to the study visit by means of a horizontal visual analogue scale (VAS) that generates a self-rated percentage of doses of all the ARV medications taken during the past 30 days.
Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv
Pharmacokinetic parameter AUC24h was assessed from the time of study medication administration upto 24 hour postdose. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
Predose Plasma Concentration (C0h) of DRV and Rtv.
Pharmacokinetic parameter C0h was assessed. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
Number of Participants Developing Mutations at Endpoint
Development of Mutations in Virologic Failures (Plasma Viral Load less than 50 Copies/mL) at endpoint.
Full Information
NCT ID
NCT00524368
First Posted
August 30, 2007
Last Updated
February 12, 2013
Sponsor
Tibotec Pharmaceuticals, Ireland
1. Study Identification
Unique Protocol Identification Number
NCT00524368
Brief Title
A Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN)
Acronym
ODIN
Official Title
A Randomized, Open-label Trial to Compare the Efficacy, Safety and Tolerability of DRV/Rtv (800mg/100mg) q.d Versus DRV/Rtv (600mg/100mg) b.i.d in Early Treatment-experienced HIV-1 Infected Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tibotec Pharmaceuticals, Ireland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to test if being treated with darunavir/ritonavir (DRV/rtv) 800/100 mg daily is as effective as being treated with DRV/rtv 600/100 mg twice daily, in early antiretroviral (ARV)-experienced patients when given along with selected optimized background regimen (OBR).
Detailed Description
This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention) study in which 590 patients will be randomly assigned to receive either DRV/rtv 800/100 mg daily or DRV/rtv 600/100 mg twice daily along with the selected OBR. An OBR will consist of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) selected by the investigator. The study will include a 4 week screening period, 48-weeks of treatment period and 4-weeks of follow-up. The study will also consists of extension phase after Week 48: in regions where DRV is not yet commercially available or reimbursed by the health care system, patients who complete the 48 weeks of treatment with DRV/rtv and who continue to benefit from this treatment, will have the opportunity to continue DRV treatment as a 600 mg twice daily dosage until DRV is reimbursed and available via the public and/or private health care system or until its development is discontinued. Safety evaluation will consists of adverse events (including specific toxicities), clinical laboratory tests, vital signs, electrocardiogram, physical and skin examination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus - Type 1
Keywords
Human immunodeficiency virus - type 1, HIV-1 Infection, TMC-114, Darunavir, Ritonavir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
590 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DRV/rtv 800/100 mg once daily
Arm Type
Experimental
Arm Description
Two 400 mg darunavir (DRV) ie, TMC114 tablets + one 100 mg ritonavir (rtv) capsule once daily.
Arm Title
DRV/rtv 600/100 mg twice daily
Arm Type
Experimental
Arm Description
One 600 mg TMC114 tablet + one 100 mg capsule of rtv twice daily.
Intervention Type
Drug
Intervention Name(s)
Darunavir (DRV)
Other Intervention Name(s)
TMC114
Intervention Description
DRV/rtv 800/100 mg once daily group: 2 tablets of 400 mg of DRV administered orally once daily. DRV/rtv 600/100 mg twice daily group: 1 tablet of 600 mg DRV administered orally twice daily.
Intervention Type
Drug
Intervention Name(s)
Ritonavir (rtv)
Other Intervention Name(s)
rtv
Intervention Description
DRV/rtv 800/100 mg once daily group: One capsule of 100 mg of ritonavir administered orally once daily. DRV/rtv 600/100 mg twice daily group: One capsule of 100 mg of ritonavir administered orally twice daily.
Primary Outcome Measure Information:
Title
Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Description
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.
Time Frame
48 Weeks
Secondary Outcome Measure Information:
Title
Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)
Description
Number of participants with confirmed plasma viral load less than 400 copies/mL at Week 48.
Time Frame
48 weeks
Title
Change in log10 Viral Load From Baseline at Week 48
Time Frame
48 weeks
Title
Time to Reach First Virologic Response
Description
Time (in weeks) to achieve viral load less than 50 copies/mL by the participants.
Time Frame
48 weeks
Title
Time to Loss of Virologic Response
Description
Time taken to lose the virologic response ie, plasma viral load less than 50 copies/mL by participants.
Time Frame
48 weeks
Title
Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks
Time Frame
48 weeks
Title
Change in CD4+ Cell Count From Baseline
Description
CD4+ cell count was calculated using the Last Observation Carried Forward (LOCF) algorithm.
Time Frame
48 Weeks
Title
Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
Description
The FAHI is a 44-item questionnaire and incorporates 5 functional scales (physical well-being, emotional well-being/living with HIV, functional and global well-being, social well-being, and cognitive functioning). Each scale included several questions (all 5 scales include total 44 questions). For each question, participants gave a score of either 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). Total FAHI imputed score is calculated by adding scores for each question. The range of total FAHI score is 0 to 176. Higher scores indicate worsening.
Time Frame
48 weeks
Title
Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48
Description
Self-reported adherence to the ARV medications was measured. The M-MASRI asks participants to report the number of doses taken, as well as the number of doses taken during the last 30 days prior to the study visit by means of a horizontal visual analogue scale (VAS) that generates a self-rated percentage of doses of all the ARV medications taken during the past 30 days.
Time Frame
48 weeks
Title
Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv
Description
Pharmacokinetic parameter AUC24h was assessed from the time of study medication administration upto 24 hour postdose. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
Time Frame
0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48.
Title
Predose Plasma Concentration (C0h) of DRV and Rtv.
Description
Pharmacokinetic parameter C0h was assessed. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
Time Frame
0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48
Title
Number of Participants Developing Mutations at Endpoint
Description
Development of Mutations in Virologic Failures (Plasma Viral Load less than 50 Copies/mL) at endpoint.
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with documented human immunodeficiency virus - Type 1 (HIV-1) infection
Patients with a viral load greater than 1,000 HIV-1 ribonucleic acid (RNA) copies/mL
Stable highly active antiretroviral therapy (HAART) regimen for at least 12 weeks at screening
In the investigator's opinion, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not a valid treatment option, because of the patient's antiretroviral (ARV) treatment history, ARV resistance testing, medication-taking behavior, safety and tolerability concerns, or other patient-related factors
Prescreening or/and screening plasma HIV-1 RNA greater than 1,000 copies/mL on HAART regimen at screening
Exclusion Criteria:
Presence of any currently active conditions that fit the definition of the World Health Organization (WHO) Clinical Stage 4, with the following exceptions: stable cutaneous kaposi's sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study time period, wasting syndrome
Patients for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine
Previous or current use of enfuvirtide (ENF), tipranavir and/or DRV
Life expectancy of less than 12 months
Pregnant or breast-feeding females
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 patient's safety or outcome of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tibotec Pharmaceuticals, Ireland Clinical Trial
Organizational Affiliation
Tibotec Pharmaceuticals, Ireland
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Beverly Hills
State/Province
California
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United States
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Oakland
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California
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United States
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Palm Springs
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California
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United States
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Fort Lauderdale
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Florida
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United States
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Fort Laudersale
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Florida
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United States
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Miami Beach
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Florida
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United States
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Miami
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Florida
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United States
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Orlando
State/Province
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United States
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Safety Harbor
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United States
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West Palm Beach
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Atlanta
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Georgia
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United States
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Macon
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Georgia
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United States
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Savannah
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Georgia
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Chicago
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Illinois
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Springfield
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Massachusetts
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Berkley
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Michigan
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Newark
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New Jersey
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Albany
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New York
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Bronx
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New York
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New York
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New York
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Rochester
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New York
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Huntersville
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North Carolina
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Winston Salem
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North Carolina
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Akron
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Ohio
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Charleston
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South Carolina
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United States
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Dallas
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Texas
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United States
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Harlingen
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Texas
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United States
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Houston
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Texas
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United States
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Buenos Aires
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Argentina
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Cordoba
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Argentina
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Guernica
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Argentina
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Neuquen
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Argentina
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Rosario
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Argentina
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Darlinghurst
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Australia
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Surry Hills
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Australia
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Wien
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Austria
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Curitiba
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Brazil
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Distrito Barao Geraldo-Campina
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Brazil
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Pinheiros
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Brazil
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Recife
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Brazil
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Rio De Janeiro
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Brazil
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Salvador
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Brazil
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Sao Paulo
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Brazil
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Providencia
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Chile
City
Santiago
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Chile
City
Lyon
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France
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Nice
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France
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Orleans Cedex 2
Country
France
City
Paris Cedex 10
Country
France
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Paris Cedex 12
Country
France
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Paris
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France
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Vandoeuvre Les Nancy
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France
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Berlin
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Germany
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Köln
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Germany
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München
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Germany
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Guatemala
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Guatemala
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Budapest
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Hungary
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Ipoh
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Malaysia
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Kuala Lumpur
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Malaysia
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Pulau Pinang
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Malaysia
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Sungai Buloh
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Malaysia
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Panama
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Panama
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San Juan
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Puerto Rico
City
Bucuresti
Country
Romania
City
Constanta
Country
Romania
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Iasi
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Romania
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Timisoara
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Romania
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Cape Town
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South Africa
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Cyrildene Johannesburg Gauteng
Country
South Africa
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Dundee
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South Africa
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Durban
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South Africa
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Houghton, Johannesburg
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South Africa
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Johannesburg
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South Africa
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Pretoria
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South Africa
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Westdene Johannesburg Gauteng
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South Africa
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Barcelona N/A
Country
Spain
City
Madrid
Country
Spain
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Kaohsiung County
Country
Taiwan
City
Taichung 407
Country
Taiwan
City
Taipei
Country
Taiwan
City
Bangkok
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Thailand
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Chiang Mai
Country
Thailand
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Khon Kaen
Country
Thailand
City
Nonthaburi
Country
Thailand
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23558157
Citation
Lathouwers E, De La Rosa G, Van de Casteele T, Baeten B, Tomaka F, De Meyer S, Picchio G. Virological analysis of once-daily and twice-daily darunavir/ritonavir in the ODIN trial of treatment-experienced patients. Antivir Ther. 2013;18(3):289-300. doi: 10.3851/IMP2569. Epub 2013 Apr 4.
Results Reference
derived
Learn more about this trial
A Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN)
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