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
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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
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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
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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 ]

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

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

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

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

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

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

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 ]

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. ]

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 ]

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


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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.  


Results Point of Contact:  
Name/Title: Medical Leader
Organization: Tibotec Pharmaceuticals, Ireland
phone: +32 015 461 497


No publications provided by Tibotec Pharmaceuticals, Ireland

Publications automatically indexed to this study:

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00524368     History of Changes
Obsolete Identifiers: NCT00613990
Other Study ID Numbers: CR013783, TMC114-TiDP31-C229, 2007-001939-61
Study First Received: August 30, 2007
Results First Received: August 27, 2010
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration
Great Britain: Research Ethics Committee