Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00530920
First received: September 17, 2007
Last updated: May 27, 2014
Last verified: May 2014
Results First Received: May 15, 2009  
Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: tipranavir
Drug: ritonavir

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given once daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Participant Flow:   Overall Study
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
STARTED     30     27     28  
COMPLETED     30     25     24  
NOT COMPLETED     0     2     4  
Randomized but not treated                 0                 2                 0  
Adverse Event                 0                 0                 3  
Withdrawal by Subject                 0                 0                 1  



  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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily
Total Total of all reporting groups

Baseline Measures
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily     Total  
Number of Participants  
[units: participants]
  30     25     28     83  
Age  
[units: years]
Mean ± Standard Deviation
  33  ± 7.54     36.9  ± 8.04     36.4  ± 8     35.3  ± 7.94  
Gender  
[units: participants]
       
Female     2     1     4     7  
Male     28     24     24     76  



  Outcome Measures
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1.  Primary:   Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))   [ Time Frame: Baseline (Day 0) to Final (Day 14) ]

Measure Type Primary
Measure Title Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))
Measure Description No text entered.
Time Frame Baseline (Day 0) to Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     28  
Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))  
[units: Log10┬ácopies/mL]
Median ( Inter-Quartile Range )
  -1.43  
  ( -1.66 to -1.24 )  
  -1.55  
  ( -1.70 to -1.37 )  
  -1.47  
  ( -1.66 to -1.09 )  


Statistical Analysis 1 for Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))
Groups [1] Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.997
Median Difference (Final Values) [4] -1.43
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  NULL HYPOTHESIS (H0): Median viral load reduction from baseline >1.2 log10 copies/mL within each group
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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.

Statistical Analysis 2 for Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))
Groups [1] Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 1
Median Difference (Final Values) [4] -1.55
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  NULL HYPOTHESIS (H0): Median viral load reduction from baseline >1.2 log10 copies/mL within each group
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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.

Statistical Analysis 3 for Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))
Groups [1] Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.998
Median Difference (Final Values) [4] -1.47
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  NULL HYPOTHESIS (H0): Median viral load reduction from baseline >1.2 log10 copies/mL within each group
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[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.



2.  Secondary:   Apparent Oral Clearance I(Cl/F) of Tipranavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Apparent Oral Clearance I(Cl/F) of Tipranavir
Measure Description Tipranavir pharmacokinetics - Clearance (CL) is defined as the dose of a drug divided by the area-under-the-concentration-time curve (AUC), ie. CL = Dose / AUC. For extravascu­lar models the fraction of dose absorbed cannot be estimated, therefore "clear­ance" for these models is actually Cl/F where F is the fraction of the drug dose which is absorbed.
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Apparent Oral Clearance I(Cl/F) of Tipranavir  
[units: L/h]
Geometric Mean ( Geometric Coefficient of Variation )
  1.45  
  ( 26.79% )  
  1.43  
  ( 26.77% )  
  1.57  
  ( 35.40% )  

No statistical analysis provided for Apparent Oral Clearance I(Cl/F) of Tipranavir



3.  Secondary:   Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)
Measure Description Tipranavir (TPV) pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  29     25     22  
Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)  
[units: h*uM]
Geometric Mean ( Geometric Coefficient of Variation )
  571.3  
  ( 27.3% )  
  289.3  
  ( 26.8% )  
  538.2  
  ( 36.4% )  

No statistical analysis provided for Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)



4.  Secondary:   Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID
Measure Description TPV pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  29     25     22  
Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID  
[units: uM]
Geometric Mean ( Geometric Coefficient of Variation )
  3.26  
  ( 92.4% )  
  10.27  
  ( 49.4% )  
  17.75  
  ( 71.7% )  

No statistical analysis provided for Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID



5.  Secondary:   Trough Concentration (Cmin) of Tipranavir   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Trough Concentration (Cmin) of Tipranavir
Measure Description TPV pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  29     25     22  
Trough Concentration (Cmin) of Tipranavir  
[units: uM]
Geometric Mean ( Geometric Coefficient of Variation )
  2.8  
  ( 106.8% )  
  12.73  
  ( 53.1% )  
  21.26  
  ( 86.8% )  

No statistical analysis provided for Trough Concentration (Cmin) of Tipranavir



6.  Secondary:   Maximum Concentration (Cmax) of Tipranavir   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Maximum Concentration (Cmax) of Tipranavir
Measure Description TPV pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  29     25     22  
Maximum Concentration (Cmax) of Tipranavir  
[units: uM]
Geometric Mean ( Geometric Coefficient of Variation )
  54.64  
  ( 20.2% )  
  36.98  
  ( 19.9% )  
  69.66  
  ( 26.5% )  

No statistical analysis provided for Maximum Concentration (Cmax) of Tipranavir



7.  Secondary:   Volume of Distribution (V/F) of Tipranavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Volume of Distribution (V/F) of Tipranavir
Measure Description Tipranavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Volume of Distribution (V/F) of Tipranavir  
[units: L]
Geometric Mean ( Geometric Coefficient of Variation )
  10.02  
  ( 14.33% )  
  9.33  
  ( 9.17% )  
  9.39  
  ( 12.34% )  

No statistical analysis provided for Volume of Distribution (V/F) of Tipranavir



8.  Secondary:   Terminal Half-Life (t1/2) of Tipranavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Terminal Half-Life (t1/2) of Tipranavir
Measure Description Tipranavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Terminal Half-Life (t1/2) of Tipranavir  
[units: h]
Geometric Mean ( Geometric Coefficient of Variation )
  4.79  
  ( 26.3% )  
  4.51  
  ( 22.4% )  
  4.14  
  ( 33.6% )  

No statistical analysis provided for Terminal Half-Life (t1/2) of Tipranavir



9.  Secondary:   Time to Cmax (Tmax) of Tipranavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Time to Cmax (Tmax) of Tipranavir
Measure Description Tipranavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Time to Cmax (Tmax) of Tipranavir  
[units: h]
Geometric Mean ( Geometric Coefficient of Variation )
  3.07  
  ( 14.7% )  
  2.34  
  ( 15.2% )  
  2.38  
  ( 16.6% )  

No statistical analysis provided for Time to Cmax (Tmax) of Tipranavir



10.  Secondary:   AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID  
[units: h*uM]
Geometric Mean ( Geometric Coefficient of Variation )
  5.05  
  ( 44.0% )  
  2.25  
  ( 47.0% )  
  1.74  
  ( 48.9% )  

No statistical analysis provided for AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID



11.  Secondary:   Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID  
[units: uM]
Geometric Mean ( Geometric Coefficient of Variation )
  0.005  
  ( 206.2% )  
  0.039  
  ( 134.0% )  
  0.025  
  ( 129.9% )  

No statistical analysis provided for Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID



12.  Secondary:   Apparent Oral Clearance I(Cl/F) of Ritonavir   [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ]

Measure Type Secondary
Measure Title Apparent Oral Clearance I(Cl/F) of Ritonavir
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 13 for QD, Day 14 for BID)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Apparent Oral Clearance I(Cl/F) of Ritonavir  
[units: L/h]
Geometric Mean ( Geometric Coefficient of Variation )
  39.6  
  ( 44.0% )  
  44.4  
  ( 47.0% )  
  57.4  
  ( 48.9% )  

No statistical analysis provided for Apparent Oral Clearance I(Cl/F) of Ritonavir



13.  Secondary:   Volume of Distribution (V/F) of Ritonavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Volume of Distribution (V/F) of Ritonavir
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Volume of Distribution (V/F) of Ritonavir  
[units: L]
Geometric Mean ( Geometric Coefficient of Variation )
  97.5  
  ( 26.8% )  
  90.8  
  ( 24.7% )  
  88.9  
  ( 28.7% )  

No statistical analysis provided for Volume of Distribution (V/F) of Ritonavir



14.  Secondary:   Terminal Half-Life (t1/2) of Ritonavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Terminal Half-Life (t1/2) of Ritonavir
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Terminal Half-Life (t1/2) of Ritonavir  
[units: Hours]
Geometric Mean ( Geometric Coefficient of Variation )
  1.71  
  ( 45.5% )  
  1.42  
  ( 59.5% )  
  1.07  
  ( 56.1% )  

No statistical analysis provided for Terminal Half-Life (t1/2) of Ritonavir



15.  Secondary:   Tmax of Ritonavir   [ Time Frame: Final (Day 14) ]

Measure Type Secondary
Measure Title Tmax of Ritonavir
Measure Description Ritonavir pharmacokinetics
Time Frame Final (Day 14)  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Tmax of Ritonavir  
[units: h]
Geometric Mean ( Geometric Coefficient of Variation )
  2.84  
  ( 23.9% )  
  2.33  
  ( 24.9% )  
  2.05  
  ( 28.8% )  

No statistical analysis provided for Tmax of Ritonavir



16.  Secondary:   Cmax of Ritonavir   [ Time Frame: Visits baseline, 5, 7, 9 and 13 or 14 ]

Measure Type Secondary
Measure Title Cmax of Ritonavir
Measure Description Ritonavir pharmacokinetics
Time Frame Visits baseline, 5, 7, 9 and 13 or 14  
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.
Treated Set, includes all patients that were randomized and were documented to have received at least one dose of investigational treatment

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Cmax of Ritonavir  
[units: uM]
Geometric Mean ( Geometric Coefficient of Variation )
  0.632  
  ( 32.5% )  
  0.346  
  ( 30.7% )  
  0.291  
  ( 34.7% )  

No statistical analysis provided for Cmax of Ritonavir



17.  Secondary:   Clinical Abnormal Findings in Laboratory and Physical Examination   [ Time Frame: Screening through the end of the study (14 days) ]

Measure Type Secondary
Measure Title Clinical Abnormal Findings in Laboratory and Physical Examination
Measure Description No text entered.
Time Frame Screening through the end of the study (14 days)  
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.
Treated set.

Reporting Groups
  Description
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily

Measured Values
    Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily     Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily     Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily  
Number of Participants Analyzed  
[units: participants]
  30     25     24  
Clinical Abnormal Findings in Laboratory and Physical Examination  
[units: participants]
     
Alanine aminotransferase (ALT) increased     0     0     1  
Aspartate aminotransferase (AST) increased     0     0     1  

No statistical analysis provided for Clinical Abnormal Findings in Laboratory and Physical Examination




  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.


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