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
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
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
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:
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).