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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00524368
First received: August 30, 2007
Last updated: February 12, 2013
Last verified: February 2013
Results First Received: August 27, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus - Type 1
Interventions: Drug: Darunavir (DRV)
Drug: Ritonavir (rtv)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
One hundred thirteen investigators in 21 countries participated in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In total 1092 participants were screened, of which 590 participants were randomly assigned and treated (294 participants were treated with DRV/rtv 800/100 mg once daily, and 296 participants with DRV/rtv 600/100 mg twice daily.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Participant Flow:   Overall Study
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
STARTED     294     296  
COMPLETED     253     248  
NOT COMPLETED     41     48  
Adverse Event                 10                 12  
Lost to Follow-up                 9                 13  
Withdrawal by Subject                 4                 5  
Non-compliant                 8                 9  
Reached a Virologic Endpoint                 3                 2  
Sponsor's Decision                 2                 0  
Ineligible to Continue the study                 2                 5  
Unspecified                 3                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily
Total Total of all reporting groups

Baseline Measures
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily     Total  
Number of Participants  
[units: participants]
  294     296     590  
Age  
[units: years]
Mean ± Standard Deviation
  40.2  ± 9.09     40.7  ± 9.50     40.5  ± 9.29  
Gender  
[units: participants]
     
Female     115     98     213  
Male     179     198     377  
Age (years) (categorical)  
[units: participants]
     
Age <= 30     35     35     70  
30 < Age <= 45     180     169     349  
45 < Age <= 55     64     72     136  
55 < Age <= 65     14     18     32  
Age > 65     1     2     3  
Hepatitis B or C Co-infection Status  
[units: participants]
     
Negative     267     255     522  
Positive     25     37     62  
Unknown     2     4     6  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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   [ Time Frame: 48 Weeks ]

Measure Type Primary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
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  
[units: Participants]
  212     210  


Statistical Analysis 1 for 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
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Regression, Logistic
P Value [4] <0.001
Difference in proportion of response [5] 0.0019
Standard Error of the mean ± 0.037
95% Confidence Interval ( -0.054 to 0.092 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Assuming a response rate of 70% at 48 weeks for both treatment groups, 306 participants were required per treatment arm to establish noninferiority of darunavir (DRV)/ritonavir (rtv) once daily versus DRV/rtv twice daily with a maximum allowable difference of 12%, with a 1-sided significance level of 0.025 and 90% power.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If at Week 48, the lower limit of the 95% two-sided confidence interval of the difference between DRV/rtv once daily and DRV/rtv twice daily exceeds -12%, non-inferiority of the DRV/rtv q.d. versus the DRV/rtv b.i.d. therapy was concluded.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  The model includes treatment as factor and baseline viral load (log10) as covariate.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  Difference in proportion of response DRV/rtv once daily minus DRV/rtv twice daily estimated from the logistic regression model.



2.  Secondary:   Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)
Measure Description Number of participants with confirmed plasma viral load less than 400 copies/mL at Week 48.
Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)  
[units: Participants]
  226     227  


Statistical Analysis 1 for Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Regression, Logistic
P Value [4] <0.001
Difference in proportion of response [5] 0.007
Standard Error of the mean ± 0.034
95% Confidence Interval ( -0.060 to 0.075 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If at Week 48, the lower limit of this 95% 2-sided CI of the difference between DRV/rtv q.d. and DRV/rtv b.i.d. exceeded -12%, noninferiority of DRV/rtv q.d. and DRV/rtv b.i.d. could be concluded.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  A logistic regression model includes treatment as fixed factor and baseline plasma viral load as a covariate.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  Difference in proportion of response between 2 treatment groups (DRV/rtv q.d. minus DRV/rtv b.i.d)



3.  Secondary:   Change in log10 Viral Load From Baseline at Week 48   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Change in log10 Viral Load From Baseline at Week 48
Measure Description No text entered.
Time Frame 48 weeks  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Change in log10 Viral Load From Baseline at Week 48  
[units: log10 copies/mL]
Median ( Full Range )
   
Log10 Viral Load at baseline     4.23  
  ( 1.73 to 6.43 )  
  4.134  
  ( 1.69 to 5.98 )  
Log10 Viral Load change from baseline at Week 48     -2.11  
  ( -4.7 to 2.0 )  
  -2.13  
  ( -4.2 to 2.4 )  


Statistical Analysis 1 for Change in log10 Viral Load From Baseline at Week 48
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.977
Difference between least square means [4] -0.003
Standard Error of the mean ± 0.094
95% Confidence Interval ( -0.188 to 0.182 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Including 1 factor for treatment, and including the covariate baseline log10 plasma viral load
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Difference between least square means between the DRV/rtv q.d. and DRV/rtv b.i.d. treatment groups at Week 48.



4.  Secondary:   Time to Reach First Virologic Response   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Time to Reach First Virologic Response
Measure Description Time (in weeks) to achieve viral load less than 50 copies/mL by the participants.
Time Frame 48 weeks  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Time to Reach First Virologic Response  
[units: Days]
Median ( Full Range )
  85  
  ( 71 to 86 )  
  85  
  ( 83 to 85 )  


Statistical Analysis 1 for Time to Reach First Virologic Response
Groups [1] All groups
Method [2] Cox proportional hazards
P Value [3] 0.917
Hazard Ratio (HR) [4] 0.990
Standard Error of the mean ± 0.094
95% Confidence Interval ( 0.824 to 1.191 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Including treatment as fixed factor and baseline plasma viral load as a covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Time to Loss of Virologic Response   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Time to Loss of Virologic Response
Measure Description Time taken to lose the virologic response ie, plasma viral load less than 50 copies/mL by participants.
Time Frame 48 weeks  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Time to Loss of Virologic Response  
[units: Days]
Mean ± Standard Error
  250.235  ± 6.598     281.743  ± 7.47  


Statistical Analysis 1 for Time to Loss of Virologic Response
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.716
Hazard Ratio, log [4] 0.945
Standard Error of the mean ± 0.154
95% Confidence Interval ( 0.699 to 1.279 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Including baseline log10 viral load as covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



6.  Secondary:   Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks
Measure Description No text entered.
Time Frame 48 weeks  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population: Observed cases

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks  
[units: log10 copies/mL]
Least Squares Mean ± Standard Error
  -1.77  ± 0.051     -1.74  ± 0.051  


Statistical Analysis 1 for Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.711
Difference in least square means [4] -0.03
Standard Error of the mean ± 0.072
95% Confidence Interval ( -0.169 to 0.115 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Including 1 factor for treatment, and including the covariate baseline log10 plasma viral load
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Difference in least square means between the 2 treatment groups (DRV/rtv q.d. and DRV/rtv b.i.d)



7.  Secondary:   Change in CD4+ Cell Count From Baseline   [ Time Frame: 48 Weeks ]

Measure Type Secondary
Measure Title Change in CD4+ Cell Count From Baseline
Measure Description CD4+ cell count was calculated using the Last Observation Carried Forward (LOCF) algorithm.
Time Frame 48 Weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population - last observation carried forward (LOCF): Intermittent missing values and missing values due to premature discontinuation were imputed with the last observation.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Change in CD4+ Cell Count From Baseline  
[units: 10e6/l]
Median ( Full Range )
   
Value at Baseline     219  
  ( 24 to 1306 )  
  236  
  ( 44 to 864 )  
CD4+ cell count change from baseline at Week 48     100  
  ( -242 to 808 )  
  94  
  ( -239 to 639 )  


Statistical Analysis 1 for Change in CD4+ Cell Count From Baseline
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.562
Difference in least square means [4] -5.95
Standard Error of the mean ± 10.26
95% Confidence Interval ( -26.09 to 14.20 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The model includes treatment as factor and baseline CD4 count and baseline viral load (log10) as covariates.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Difference in least square means DRV/rtv once daily minus DRV/rtv twice daily estimated from the ANCOVA model.



8.  Secondary:   Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT) population - last observation carried forward (LOCF): Intermittent missing values and missing values due to premature discontinuation were imputed with the last observation.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score  
[units: Scores on a scale]
Median ( Full Range )
   
FAHI score at baseline     129  
  ( 31 to 175 )  
  123.5  
  ( 33 to 174 )  
Change from baseline in FAHI score at Week 48     2.5  
  ( -74 to 81 )  
  0.0  
  ( -75 to 81 )  


Statistical Analysis 1 for Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.761
Difference in least square means [4] 0.55
Standard Error of the mean ± 1.79
95% Confidence Interval ( -2.97 to 4.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Including factors for treatment, and baseline log10 plasma viral load and baseline FAHI score as covariates
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Difference in least square means DRV/rtv once daily minus DRV/rtv twice daily estimated from the ANCOVA model.



9.  Secondary:   Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population: Participants who were randomized and who received at least 1 dose of study medication.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48  
[units: Percentage of participants]
   
Adherent     67.4     60.3  
Non-adherent     32.6     39.7  

No statistical analysis provided for Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48



10.  Secondary:   Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv   [ 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. ]

Measure Type Secondary
Measure Title Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population: Participants who were randomized and who received at least 1 dose of study medication.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv  
[units: ng*h/mL]
Median ( Full Range )
   
Population Pharmacokinetic Estimates of DRV     87788  
  ( 45456 to 236920 )  
  109401  
  ( 48934 to 323820 )  
Population Pharmacokinetic Estimates of rtv     5776  
  ( 1801 to 39027 )  
  12588  
  ( 3404 to 44762 )  

No statistical analysis provided for Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv



11.  Secondary:   Predose Plasma Concentration (C0h) of DRV and Rtv.   [ 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 ]

Measure Type Secondary
Measure Title Predose Plasma Concentration (C0h) of DRV and Rtv.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population: Participants who were randomized and who received at least 1 dose of study medication.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Predose Plasma Concentration (C0h) of DRV and Rtv.  
[units: ng/mL]
Median ( Full Range )
   
Population Pharmacokinetic Estimates of DRV     1896  
  ( 184 to 7881 )  
  3197  
  ( 250 to 11865 )  
Population Pharmacokinetic Estimates of rtv     59  
  ( 6 to 1049 )  
  307  
  ( 41 to 1657 )  

No statistical analysis provided for Predose Plasma Concentration (C0h) of DRV and Rtv.



12.  Secondary:   Number of Participants Developing Mutations at Endpoint   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Number of Participants Developing Mutations at Endpoint
Measure Description Development of Mutations in Virologic Failures (Plasma Viral Load less than 50 Copies/mL) at endpoint.
Time Frame 48 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population: Participants who were randomized and who received at least 1 dose of study medication.

Reporting Groups
  Description
DRV/Rtv 800/100 mg Once Daily Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values
    DRV/Rtv 800/100 mg Once Daily     DRV/Rtv 600/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  294     296  
Number of Participants Developing Mutations at Endpoint  
[units: Participants]
   
DRV resistance-associated mutation (RAM)     1     0  
Primary (major) protease inhibitor (PI) mutations     1     0  
Protease inhibitor (PI) RAMs     7     4  
Nucleoside reverse transcriptase inhibitor RAMs     4     3  

No statistical analysis provided for Number of Participants Developing Mutations at Endpoint




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information