Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00530920
First received: September 17, 2007
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
HIV Infections
Drug: tipranavir
Drug: ritonavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF)) [ Time Frame: Baseline (Day 0) to Final (Day 14) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Apparent Oral Clearance I(Cl/F) of Tipranavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID) [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    TPV pharmacokinetics

  • Trough Concentration (Cmin) of Tipranavir [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    TPV pharmacokinetics

  • Maximum Concentration (Cmax) of Tipranavir [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    TPV pharmacokinetics

  • Volume of Distribution (V/F) of Tipranavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Tipranavir pharmacokinetics

  • Terminal Half-Life (t1/2) of Tipranavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Tipranavir pharmacokinetics

  • Time to Cmax (Tmax) of Tipranavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Tipranavir pharmacokinetics

  • AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Apparent Oral Clearance I(Cl/F) of Ritonavir [ Time Frame: Final (Day 13 for QD, Day 14 for BID) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Volume of Distribution (V/F) of Ritonavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Terminal Half-Life (t1/2) of Ritonavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Tmax of Ritonavir [ Time Frame: Final (Day 14) ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Cmax of Ritonavir [ Time Frame: Visits baseline, 5, 7, 9 and 13 or 14 ] [ Designated as safety issue: No ]
    Ritonavir pharmacokinetics

  • Clinical Abnormal Findings in Laboratory and Physical Examination [ Time Frame: Screening through the end of the study (14 days) ] [ Designated as safety issue: Yes ]

Enrollment: 85
Study Start Date: October 2007
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530920

Locations
Germany
1182.107.49002 Boehringer Ingelheim Investigational Site
Berlin, Germany
1182.107.49004 Boehringer Ingelheim Investigational Site
Berlin, Germany
1182.107.49003 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1182.107.49001 Boehringer Ingelheim Investigational Site
München, Germany
Italy
1182.107.39001 Boehringer Ingelheim Investigational Site
Antella (fi), Italy
1182.107.39009 Boehringer Ingelheim Investigational Site
Bari, Italy
1182.107.39007 Boehringer Ingelheim Investigational Site
Ferrara, Italy
1182.107.39011 Boehringer Ingelheim Investigational Site
Palermo, Italy
Spain
1182.107.34001 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1182.107.34002 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1182.107.34003 Boehringer Ingelheim Investigational Site
L'Hospitalet de Llobregat, Spain
1182.107.34004 Boehringer Ingelheim Investigational Site
Madrid, Spain
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00530920     History of Changes
Other Study ID Numbers: 1182.107
Study First Received: September 17, 2007
Results First Received: May 15, 2009
Last Updated: May 27, 2014
Health Authority: Italy: Comitato Etico Per La Sperimentazione Clinica Dei Medicinali Az. San. - Firenze

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Tipranavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014