Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: tipranavir; ritonavir
Intervention MeSH terms: Ritonavir; Tipranavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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).