Safety and Antiviral Activity of TPV in HCV and/or HBV HIV Coinfected Patients TDM Randomised Pilot Evaluation

This study has been terminated.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00447902
First received: March 14, 2007
Last updated: April 25, 2014
Last verified: April 2014
Results First Received: September 25, 2009  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy 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
With FDA and EMEA agreement, the trial was prematurely discontinued before reaching the target number of patients to be entered due to poor recruitment. For this reason analyzing and reporting data as planned for primary and secondary endpoints have not been performed. No objectives were reached and no conclusion can be drawn from this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One patient has been randomised by mistake in Brasil and so he was not treated

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Participant Flow:   Overall Study
    Standard of Care     Therapeutic Drug Monitoring  
STARTED     5     6  
COMPLETED     1     0  
NOT COMPLETED     4     6  
Adverse Event                 0                 3  
Protocol Violation                 1                 0  
Withdrawal by Subject                 0                 1  
included patients who discontinued                 1                 1  
Lack of Efficacy                 2                 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.
No text entered.

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules
Total Total of all reporting groups

Baseline Measures
    Standard of Care     Therapeutic Drug Monitoring     Total  
Number of Participants  
[units: participants]
  4     6     10  
Age  
[units: years]
Mean ± Standard Deviation
  46.00  ± 2.90     45.20  ± 5.40     45.50  ± 4.40  
Gender [1]
[units: participants]
     
Female     1     1     2  
Male     3     5     8  
[1] Included patients who discontinued due to early termination



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Treatment Response at Week 48   [ Time Frame: 48 weeks ]

Measure Type Primary
Measure Title Treatment Response at Week 48
Measure Description Treatment response is a confirmed virologic response, defined as a viral load less than 50 copies/mL at two consecutive measurements at least 5 days apart, without death, permanent discontinuation, or introduction of a new antiretroviral
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Treatment Response at Week 48          

No statistical analysis provided for Treatment Response at Week 48



2.  Primary:   The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.   [ Time Frame: From the start of the study through 48 weeks. ]

Measure Type Primary
Measure Title The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.
Measure Description Dose-limiting hepatotoxicity was defined as Grade 4 ALT or AST elevation confirmed in 48h or any evocative symptoms or signs of hepatitis, if it not clearly attributable to another cause. Patients who experienced dose-limiting hepatotoxicity stopped TPV/r and were considered treatment failures for the analysis.
Time Frame From the start of the study through 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.
No text entered.

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.          

No statistical analysis provided for The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.



3.  Secondary:   Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit   [ Time Frame: After 4 weeks of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit
Measure Description Virologic response defined as viral load less than 50 copies/mL
Time Frame After 4 weeks of treatment until the end of the trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit          

No statistical analysis provided for Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit



4.  Secondary:   Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48   [ Time Frame: 24 and 48 weeks ]

Measure Type Secondary
Measure Title Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48
Measure Description Patients with a viral load of less than 400 copies/mL at Weeks 24 and 48 as measured from a plasma sample.
Time Frame 24 and 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48          

No statistical analysis provided for Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48



5.  Secondary:   Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit   [ Time Frame: After 4 weeks of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit
Measure Description Patients with a viral load of less than 400 copies/mL at each visit as measured from a plasma sample.
Time Frame After 4 weeks of treatment until the end of the trial  
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.
No text entered.

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit          

No statistical analysis provided for Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit



6.  Secondary:   Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48   [ Time Frame: Baseline, 24 and 48 weeks ]

Measure Type Secondary
Measure Title Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
Measure Description Occurrence of greater than or equal to 1 log10 drop in viral load from baseline at all visits, including visits at Weeks 24 and 48
Time Frame Baseline, 24 and 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48          

No statistical analysis provided for Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48



7.  Secondary:   Change in Viral Load From Baseline at Each Visit   [ Time Frame: After 4 weeks of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Change in Viral Load From Baseline at Each Visit
Measure Description Change in viral load (measured from a plasma sample) from baseline at each visitPatients with a viral load of less than 400 copies/mL at each visit as .
Time Frame After 4 weeks of treatment until the end of the trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Change in Viral Load From Baseline at Each Visit          

No statistical analysis provided for Change in Viral Load From Baseline at Each Visit



8.  Secondary:   Time to Treatment Failure   [ Time Frame: After Day 1 of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Time to Treatment Failure
Measure Description For patients who never achieve a confirmed virologic response, time to treatment failure is defined as 0. For patients who achieve a confirmed virologic response, time to treatment failure is the earliest time of either: death, permanent discontinuation of the study drug or loss to follow-up, introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug, but not the study drug, or first occurrence of a VL >50 copies/mL at two consecutive measurements after having achieved a VL <50 copies/mL.
Time Frame After Day 1 of treatment until the end of the trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Time to Treatment Failure          

No statistical analysis provided for Time to Treatment Failure



9.  Secondary:   Time to New AIDS or AIDS Related Progression Event or Death   [ Time Frame: After Day 1 of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Time to New AIDS or AIDS Related Progression Event or Death
Measure Description Time to new AIDS or AIDS related progression event or death as defined by AIDS defining and/or AIDS-related illnesses.
Time Frame After Day 1 of treatment until the end of the trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Time to New AIDS or AIDS Related Progression Event or Death          

No statistical analysis provided for Time to New AIDS or AIDS Related Progression Event or Death



10.  Secondary:   Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48   [ Time Frame: after 2 weeks of treatment till Week 48 ]

Measure Type Secondary
Measure Title Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48
Measure Description Change from baseline to Week 48 for CD4+ and CD8+ cell counts. Samples were obtained for CD4+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Time Frame after 2 weeks of treatment till Week 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48          

No statistical analysis provided for Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48



11.  Secondary:   Change in Ratio of CD38+/CD8+ From Baseline to Week 48   [ Time Frame: after 2 weeks of treatment till Week 48 ]

Measure Type Secondary
Measure Title Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Measure Description Change from baseline to Week 48 for the ratio of CD38+ to CD8+ cell counts. Samples were obtained for CD38+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Time Frame after 2 weeks of treatment till Week 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Change in Ratio of CD38+/CD8+ From Baseline to Week 48          

No statistical analysis provided for Change in Ratio of CD38+/CD8+ From Baseline to Week 48



12.  Secondary:   Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.   [ Time Frame: after 2 weeks of treatment till Week 48 ]

Measure Type Secondary
Measure Title Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.
Measure Description Change from baseline to Week 48 for the ratio of CD3+ CD8+ CD38+ HLA DR . Samples were obtained for CD3+ CD8+ CD38+ HLA DR as measurements of viral suppression during antiretroviral therapy.
Time Frame after 2 weeks of treatment till Week 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.          

No statistical analysis provided for Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.



13.  Secondary:   Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48   [ Time Frame: after 2 weeks of treatment till Week 48 ]

Measure Type Secondary
Measure Title Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Measure Description Tipranavir (TPV) and Ritonavir (RTV) trough concentrations from plasma samples at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Time Frame after 2 weeks of treatment till Week 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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48          

No statistical analysis provided for Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48



14.  Secondary:   Patients Adherence With Study Medication Based on Pill Count   [ Time Frame: After 4 weeks of treatment until the end of the trial ]

Measure Type Secondary
Measure Title Patients Adherence With Study Medication Based on Pill Count
Measure Description number of pills actually taken divided by the planned number of pills the patient should take
Time Frame After 4 weeks of treatment until the end of the trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Patients Adherence With Study Medication Based on Pill Count          

No statistical analysis provided for Patients Adherence With Study Medication Based on Pill Count



15.  Secondary:   Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured   [ Time Frame: After 2 weeks of treatment until the end of trial ]

Measure Type Secondary
Measure Title Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
Measure Description A high inhibitory quotient (IQ), the ratio of trough plasma drug concentration to the protein-adjusted viral IC50, is a useful indicator of the potential efficacy margin of antiretroviral drugs. The IQ for TPV is calculated by the formula IQ = TPV Ctrough / (3.75 x Z x fold change of the patients virus), where Z = wild type control IC50 IIIB.
Time Frame After 2 weeks of treatment until the end of trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured          

No statistical analysis provided for Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured



16.  Secondary:   Occurrence of Tipranavir (TPV) Trough Concentration >120 μM   [ Time Frame: After 2 weeks of treatment until the end of trial ]

Measure Type Secondary
Measure Title Occurrence of Tipranavir (TPV) Trough Concentration >120 μM
Measure Description Patients with TPV trough above 120 μM are at high risk of developing a Grade 3 or 4 ALT or AST elevations. The risk of Grade 3 or greater transaminase elevations appeared to be uniform at TPV trough concentration below 120 μM. Hence, for this study the TPV trough should be maintained below 120 μM.
Time Frame After 2 weeks of treatment until the end of trial  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Occurrence of Tipranavir (TPV) Trough Concentration >120 μM          

No statistical analysis provided for Occurrence of Tipranavir (TPV) Trough Concentration >120 μM



17.  Secondary:   Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4   [ Time Frame: Week 4 ]

Measure Type Secondary
Measure Title Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4
Measure Description Post-dose Tipranavir (TPV) and Ritonavir (RTV) plasma concentrations at Week 4
Time Frame Week 4  
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.
The trial has been stopped due to a poor enrollment

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  0     0  
Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4          

No statistical analysis provided for Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4



18.  Secondary:   Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements   [ Time Frame: Baseline through 48 weeks ]

Measure Type Secondary
Measure Title Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements
Measure Description Frequency of patients (%) with possible clinically significant abnormalities of laboratory measurements (haematology, differentials (automatic and absolute), coagulation, electrolytes, enzymes, substrates, urinalysis, serology and T-cells)
Time Frame Baseline through 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.
No text entered.

Reporting Groups
  Description
Standard of Care Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules
Therapeutic Drug Monitoring Tipranavir (TPV) 500mg and Ritonavir (RTV) 200mg BID capsules as initial dose, increased to TPV/r 750mg/200mg BID capsules, or decreased to TPV/r 500mg/100mg BID capsules or TPV/r 250mg/200mg BID capsules

Measured Values
    Standard of Care     Therapeutic Drug Monitoring  
Number of Participants Analyzed  
[units: participants]
  4     6  
Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements  
[units: percentage¬†of¬†participants]
   
Hematocrit - decrease     25.0     16.7  
Red Blood Cell count - decrease     25.0     0  
Prothrombin time - increase     0     20  
AST/GOT, SGOT - increase     50.0     33.3  
ALT/GPT, SGPT - increase     25.0     33.3  
Lipase - increase     0     16.7  
Bilirubin, total - increase     0     16.7  
Bilirubin, direct - increase     0     16.7  
Triglyceride - increase     0     25  

No statistical analysis provided for Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements




  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
Due to an early termination of the trial no analysis has been performed for primary and secondary endpoints


  More Information