Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients

A Multicenter, Randomized, Open Label, Clinical Trial to Evaluate Three Doses of Tipranavir Boosted With Ritonavir (500 mg/200 mg qd, 250 mg/100 mg Bid and 500 mg/100 mg Bid) by Assessing the Steady-state Pharmacokinetics and Short-term Efficacy and Safety in HIV-1 Positive Treatment naïve Patients

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00530920

Enrollment

Registered

2007-09-18

Start date

2007-10-31

Completion date

Unknown

Last updated

2014-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Brief summary

The purpose of this study is to identify an optimal dose combination(s) of tipranavir (TPV) and ritonavir (RTV) for antiretroviral treatment naïve HIV-1 infected patients that can be used in pivotal trial by assessing the steady-state pharmacokinetics and short-term efficacy and safety

Interventions

DRUGtipranavir

DRUGritonavir

Study design

Intervention model

PARALLEL

Primary purpose

TREATMENT

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation. * HIV-1 infected men and non-pregnant women who are treatment naïve, with positive serology (EIA) confirmed by Western blot. * Age \> 18 and \< 65 years. * CD4 \> 200 cells/mm3 * Viral load (HIV-1 mRNA viral load) \> 5,000 copies/mL. * Ability to swallow multiple large capsules without difficulty. * Acceptable laboratory values that indicate adequate baseline organ function at screening visit. * Laboratory values are considered to be acceptable if the severity of any parameter is = \< Grade 2, based on the DAIDS/ACTG Grading Scale (see Appendix 10.2). * Acceptable medical history, physical examination, and 12-lead ECG at screening * Willingness to abstain from the following starting 2 weeks prior to administration of any study medication and up until the end of the study: o Grapefruit or grapefruit juice, Seville oranges, St. John's Wort, and Milk Thistle. * Willingness to abstain from alcohol 3 days prior to administration of any study medication up to the end of the study. * Willingness to abstain from the following starting 3 days prior to PK sampling: o Garlic supplements and methylxanthine containing foods or drinks (including coffee, tea, cola, energy drinks, chocolate, etc.). * Willingness to abstain from over-the-counter herbal medications for the duration of the study. * Willingness to abstain from any over the counter medication 7 days prior to administration of any study medication (including vitamins, minerals, dietary supplements and antacids) during the study until completion of the post study assessments.

Exclusion criteria

* Female patients of reproductive potential who: * Have positive serum pregnancy test. * Have not been using a barrier method of contraception for at least 3 months prior to participation in the study. * Are not willing to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and 60 days after completion/termination of the trial. * Are breast-feeding. * Suspected or documented seroconversion within last 6 months * Participation in another trial with an investigational medicine within 2 months prior to Day 0 of this study. * Use of any pharmacological contraceptive (including oral, patch or injectable contraceptives) within 1 month prior to Day 0 and for the duration of the study. * Use of hormone replacement therapy within 1 month prior to Day 0 and anytime during the study. * History of acute illness within 30 days prior to Day 0. * Have evidence of active or acute HBV or HCV. * Alcohol or substance abuse within 1 year prior to screening or during the study. * Patients with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering TPV. * Patients who have taken (within 7 days prior to Day 0) any over-the-counter or prescription medication that, in the opinion of the investigator in consultation with the BI clinical monitor, might interfere with absorption, distribution, or metabolism of the study medications. * Known hypersensitivity to any ingredients of the test drug. * Inability to adhere to the protocol. * Genotypic resistance to tipranavir (defined as a TPV mutation score \> 4).

Design outcomes

Primary

Measure	Time frame
Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))	Baseline (Day 0) to Final (Day 14)

Secondary

Measure	Time frame	Description
Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)	Final (Day 13 for QD, Day 14 for BID)	Tipranavir (TPV) pharmacokinetics
Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID	Final (Day 13 for QD, Day 14 for BID)	TPV pharmacokinetics
Trough Concentration (Cmin) of Tipranavir	Final (Day 13 for QD, Day 14 for BID)	TPV pharmacokinetics
Maximum Concentration (Cmax) of Tipranavir	Final (Day 13 for QD, Day 14 for BID)	TPV pharmacokinetics
Volume of Distribution (V/F) of Tipranavir	Final (Day 14)	Tipranavir pharmacokinetics
Terminal Half-Life (t1/2) of Tipranavir	Final (Day 14)	Tipranavir pharmacokinetics
Time to Cmax (Tmax) of Tipranavir	Final (Day 14)	Tipranavir pharmacokinetics
Apparent Oral Clearance I(Cl/F) of Tipranavir	Final (Day 14)	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 extravascu-lar models the fraction of dose absorbed cannot be estimated, therefore clear-ance for these models is actually Cl/F where F is the fraction of the drug dose which is absorbed.
Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID	Final (Day 13 for QD, Day 14 for BID)	Ritonavir pharmacokinetics
Apparent Oral Clearance I(Cl/F) of Ritonavir	Final (Day 13 for QD, Day 14 for BID)	Ritonavir pharmacokinetics
Volume of Distribution (V/F) of Ritonavir	Final (Day 14)	Ritonavir pharmacokinetics
Terminal Half-Life (t1/2) of Ritonavir	Final (Day 14)	Ritonavir pharmacokinetics
Tmax of Ritonavir	Final (Day 14)	Ritonavir pharmacokinetics
Cmax of Ritonavir	Visits baseline, 5, 7, 9 and 13 or 14	Ritonavir pharmacokinetics
Clinical Abnormal Findings in Laboratory and Physical Examination	Screening through the end of the study (14 days)	—
AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID	Final (Day 13 for QD, Day 14 for BID)	Ritonavir pharmacokinetics

Countries

Germany, Italy, Spain

Participant flow

Participants by arm

Arm	Count
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily Tipranavir 500 mg boosted with ritonavir 200 mg given once daily	30
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily Tipranavir 250 mg boosted with ritonavir 100 mg given twice daily	25
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily Tipranavir 500 mg boosted with ritonavir 100 mg given twice daily	28
Total	83

Withdrawals & dropouts

Period	Reason	FG001	FG002
Overall Study	Adverse Event	0	3
Overall Study	Randomized but not treated	2	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	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
Age, Continuous	33 years STANDARD_DEVIATION 7.54	36.9 years STANDARD_DEVIATION 8.04	36.4 years STANDARD_DEVIATION 8	35.3 years STANDARD_DEVIATION 7.94
Sex: Female, Male Female	2 Participants	1 Participants	4 Participants	7 Participants
Sex: Female, Male Male	28 Participants	24 Participants	24 Participants	76 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	17 / 30	9 / 25	15 / 28
serious Total, serious adverse events	0 / 30	0 / 25	1 / 28

Outcome results

Primary

Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))

Time frame: Baseline (Day 0) to Final (Day 14)

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

Arm	Measure	Value (MEDIAN)
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))	-1.43 Log10 copies/mL
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))	-1.55 Log10 copies/mL
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))	-1.47 Log10 copies/mL

Comparison: NULL HYPOTHESIS (H0): Median viral load reduction from baseline \>1.2 log10 copies/mL within each groupp-value: 0.997Wilcoxon (Mann-Whitney)

Comparison: NULL HYPOTHESIS (H0): Median viral load reduction from baseline \>1.2 log10 copies/mL within each groupp-value: 1Wilcoxon (Mann-Whitney)

Comparison: NULL HYPOTHESIS (H0): Median viral load reduction from baseline \>1.2 log10 copies/mL within each groupp-value: 0.998Wilcoxon (Mann-Whitney)

Secondary

Apparent Oral Clearance I(Cl/F) of Ritonavir

Ritonavir pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Apparent Oral Clearance I(Cl/F) of Ritonavir	39.6 L/h	Geometric Coefficient of Variation 44
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Apparent Oral Clearance I(Cl/F) of Ritonavir	44.4 L/h	Geometric Coefficient of Variation 47
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Apparent Oral Clearance I(Cl/F) of Ritonavir	57.4 L/h	Geometric Coefficient of Variation 48.9

Secondary

Apparent Oral Clearance I(Cl/F) of Tipranavir

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 extravascu-lar models the fraction of dose absorbed cannot be estimated, therefore clear-ance for these models is actually Cl/F where F is the fraction of the drug dose which is absorbed.

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Apparent Oral Clearance I(Cl/F) of Tipranavir	1.45 L/h	Geometric Coefficient of Variation 26.79
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Apparent Oral Clearance I(Cl/F) of Tipranavir	1.43 L/h	Geometric Coefficient of Variation 26.77
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Apparent Oral Clearance I(Cl/F) of Tipranavir	1.57 L/h	Geometric Coefficient of Variation 35.4

Secondary

Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)

Tipranavir (TPV) pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)	571.3 h*uM	Geometric Coefficient of Variation 27.3
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)	289.3 h*uM	Geometric Coefficient of Variation 26.8
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)	538.2 h*uM	Geometric Coefficient of Variation 36.4

Secondary

AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID

Ritonavir pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID	5.05 h*uM	Geometric Coefficient of Variation 44
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID	2.25 h*uM	Geometric Coefficient of Variation 47
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID	1.74 h*uM	Geometric Coefficient of Variation 48.9

Secondary

Clinical Abnormal Findings in Laboratory and Physical Examination

Time frame: Screening through the end of the study (14 days)

Population: Treated set.

Arm	Measure	Group	Value (NUMBER)
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Alanine aminotransferase (ALT) increased	0 participants
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Aspartate aminotransferase (AST) increased	0 participants
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Alanine aminotransferase (ALT) increased	0 participants
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Aspartate aminotransferase (AST) increased	0 participants
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Alanine aminotransferase (ALT) increased	1 participants
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Clinical Abnormal Findings in Laboratory and Physical Examination	Aspartate aminotransferase (AST) increased	1 participants

Secondary

Cmax of Ritonavir

Ritonavir pharmacokinetics

Time frame: Visits baseline, 5, 7, 9 and 13 or 14

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Cmax of Ritonavir	0.632 uM	Geometric Coefficient of Variation 32.5
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Cmax of Ritonavir	0.346 uM	Geometric Coefficient of Variation 30.7
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Cmax of Ritonavir	0.291 uM	Geometric Coefficient of Variation 34.7

Secondary

Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID

TPV pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID	3.26 uM	Geometric Coefficient of Variation 92.4
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID	10.27 uM	Geometric Coefficient of Variation 49.4
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID	17.75 uM	Geometric Coefficient of Variation 71.7

Secondary

Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID

Ritonavir pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID	0.005 uM	Geometric Coefficient of Variation 206.2
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID	0.039 uM	Geometric Coefficient of Variation 134
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID	0.025 uM	Geometric Coefficient of Variation 129.9

Secondary

Maximum Concentration (Cmax) of Tipranavir

TPV pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Maximum Concentration (Cmax) of Tipranavir	54.64 uM	Geometric Coefficient of Variation 20.2
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Maximum Concentration (Cmax) of Tipranavir	36.98 uM	Geometric Coefficient of Variation 19.9
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Maximum Concentration (Cmax) of Tipranavir	69.66 uM	Geometric Coefficient of Variation 26.5

Secondary

Terminal Half-Life (t1/2) of Ritonavir

Ritonavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Terminal Half-Life (t1/2) of Ritonavir	1.71 Hours	Geometric Coefficient of Variation 45.5
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Terminal Half-Life (t1/2) of Ritonavir	1.42 Hours	Geometric Coefficient of Variation 59.5
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Terminal Half-Life (t1/2) of Ritonavir	1.07 Hours	Geometric Coefficient of Variation 56.1

Secondary

Terminal Half-Life (t1/2) of Tipranavir

Tipranavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Terminal Half-Life (t1/2) of Tipranavir	4.79 h	Geometric Coefficient of Variation 26.3
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Terminal Half-Life (t1/2) of Tipranavir	4.51 h	Geometric Coefficient of Variation 22.4
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Terminal Half-Life (t1/2) of Tipranavir	4.14 h	Geometric Coefficient of Variation 33.6

Secondary

Time to Cmax (Tmax) of Tipranavir

Tipranavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Time to Cmax (Tmax) of Tipranavir	3.07 h	Geometric Coefficient of Variation 14.7
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Time to Cmax (Tmax) of Tipranavir	2.34 h	Geometric Coefficient of Variation 15.2
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Time to Cmax (Tmax) of Tipranavir	2.38 h	Geometric Coefficient of Variation 16.6

Secondary

Tmax of Ritonavir

Ritonavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Tmax of Ritonavir	2.84 h	Geometric Coefficient of Variation 23.9
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Tmax of Ritonavir	2.33 h	Geometric Coefficient of Variation 24.9
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Tmax of Ritonavir	2.05 h	Geometric Coefficient of Variation 28.8

Secondary

Trough Concentration (Cmin) of Tipranavir

TPV pharmacokinetics

Time frame: Final (Day 13 for QD, Day 14 for BID)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Trough Concentration (Cmin) of Tipranavir	2.8 uM	Geometric Coefficient of Variation 106.8
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Trough Concentration (Cmin) of Tipranavir	12.73 uM	Geometric Coefficient of Variation 53.1
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Trough Concentration (Cmin) of Tipranavir	21.26 uM	Geometric Coefficient of Variation 86.8

Secondary

Volume of Distribution (V/F) of Ritonavir

Ritonavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Volume of Distribution (V/F) of Ritonavir	97.5 L	Geometric Coefficient of Variation 26.8
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Volume of Distribution (V/F) of Ritonavir	90.8 L	Geometric Coefficient of Variation 24.7
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Volume of Distribution (V/F) of Ritonavir	88.9 L	Geometric Coefficient of Variation 28.7

Secondary

Volume of Distribution (V/F) of Tipranavir

Tipranavir pharmacokinetics

Time frame: Final (Day 14)

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Tipranavir With Ritonavir (TPV/r) 500/200 mg Once Daily	Volume of Distribution (V/F) of Tipranavir	10.02 L	Geometric Coefficient of Variation 14.33
Tipranavir With Ritonavir (TPV/r) 250/100 mg Twice Daily	Volume of Distribution (V/F) of Tipranavir	9.33 L	Geometric Coefficient of Variation 9.17
Tipranavir With Ritonavir (TPV/r) 500/100 mg Twice Daily	Volume of Distribution (V/F) of Tipranavir	9.39 L	Geometric Coefficient of Variation 12.34

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))

Apparent Oral Clearance I(Cl/F) of Ritonavir

Apparent Oral Clearance I(Cl/F) of Tipranavir

Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)

AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID

Clinical Abnormal Findings in Laboratory and Physical Examination

Cmax of Ritonavir

Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID

Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID

Maximum Concentration (Cmax) of Tipranavir

Terminal Half-Life (t1/2) of Ritonavir

Terminal Half-Life (t1/2) of Tipranavir

Time to Cmax (Tmax) of Tipranavir

Tmax of Ritonavir

Trough Concentration (Cmin) of Tipranavir

Volume of Distribution (V/F) of Ritonavir

Volume of Distribution (V/F) of Tipranavir