Clinical trial NCT00530920: Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-09-18
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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).

Primary outcomes:
measure: Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))
timeFrame: Baseline (Day 0) to Final (Day 14)
Secondary outcomes:
measure: Apparent Oral Clearance I(Cl/F) of Tipranavir
timeFrame: Final (Day 14)
measure: Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Trough Concentration (Cmin) of Tipranavir
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Maximum Concentration (Cmax) of Tipranavir
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Volume of Distribution (V/F) of Tipranavir
timeFrame: Final (Day 14)
measure: Terminal Half-Life (t1/2) of Tipranavir
timeFrame: Final (Day 14)
measure: Time to Cmax (Tmax) of Tipranavir
timeFrame: Final (Day 14)
measure: AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Apparent Oral Clearance I(Cl/F) of Ritonavir
timeFrame: Final (Day 13 for QD, Day 14 for BID)
measure: Volume of Distribution (V/F) of Ritonavir
timeFrame: Final (Day 14)
measure: Terminal Half-Life (t1/2) of Ritonavir
timeFrame: Final (Day 14)
measure: Tmax of Ritonavir
timeFrame: Final (Day 14)
measure: Cmax of Ritonavir
timeFrame: Visits baseline, 5, 7, 9 and 13 or 14
measure: Clinical Abnormal Findings in Laboratory and Physical Examination
timeFrame: Screening through the end of the study (14 days)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1182.107.49002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1182.107.49004 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1182.107.49003 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1182.107.49001 Boehringer Ingelheim Investigational Site
city: Antella (fi)
country: Italy
facility: 1182.107.39001 Boehringer Ingelheim Investigational Site
city: Bari
country: Italy
facility: 1182.107.39009 Boehringer Ingelheim Investigational Site
city: Ferrara
country: Italy
facility: 1182.107.39007 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1182.107.39011 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1182.107.34001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1182.107.34002 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: 1182.107.34003 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1182.107.34004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: