Clinical Trials

MainTitle

Effects of Tipranavir/Ritonavir on the Pharmacokinetic Characteristics of Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects

This study has been completed
Sponsor
Boehringer Ingelheim


Information provided by (Responsible Party)
Boehringer Ingelheim
ClinicalTrials.gov Identifier
NCT02251223

First received: September 25, 2014
Last updated: September 25, 2014
Last Verified: September 2014
History of Changes
Purpose

Purpose

Primary: Sequentially determine the effects of three dose combinations of tipranavir (TPV) / ritonavir (RTV) (administered b.i.d.), TPV 1250 mg/RTV 100 mg vs. TPV 750 mg/RTV 100 mg vs. TPV 250 mg/RTV 200 mg on the steady-state pharmacokinetics of zidovudine, lamivudine, stavudine, didanosine, abacavir, nevirapine and efavirenz at approved doses. The three treatment groups will be enrolled sequentially starting with the highest tipranavir dosage group first and ending with the lowest tipranavir dosage group.

Secondary: A) To assess the effects of zidovudine, lamivudine, stavudine, didanosine, abacavir, nevirapine, and efavirenz on the pharmacokinetics of tipranavir/ritonavir compared to historical controls.

B) To assess the safety of three tipranavir/ritonavir combinations when used in combination with protocol defined antiretrovirals.

Condition Intervention Phase
HIV Infections

Drug : Tipranavir low dose
Drug : Tipranavir medium dose
Drug : Tipranavir high dose
Drug : Ritonavir low dose
Drug : Ritonavir high dose
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: An Open Label Multinational Study of the Effects of Three Dose Pairs of Tipranavir/Ritonavir (b.i.d.) on the Pharmacokinetic Characteristics of Protocol -Defined, Baseline, Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects.

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures

  • Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI) [ Time Frame: baseline, up to day 23 ]
    stratified by substance
  • Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI) [ Time Frame: baseline, up to day 22 ]
    stratified by substance
  • Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI) [ Time Frame: baseline, up to day 22 ]
Secondary Outcome Measures:
  • Cmin,ss [ Time Frame: up to day 23 ]
    stratified by substance
  • AUC0-τ [ Time Frame: up to day 23 ]
    stratified by substance
  • Maximum plasma concentration (Cmax) [ Time Frame: up to day 23 ]
    stratified by substance
  • Time of maximum plasma concentration (Tmax) [ Time Frame: up to day 23 ]
    stratified by substance
  • Oral clearance (Cl/F) [ Time Frame: up to day 23 ]
    stratified by substance
  • Apparent terminal half life (t1/2) [ Time Frame: up to day 23 ]
    stratified by substance
  • Change in CD4 cell count [ Time Frame: up to day 23 ]
  • Change in HIV-1 RNA levels [ Time Frame: up to day 23 ]
  • Number of patients with clinically significant findings in laboratory tests [ Time Frame: up to 25 weeks ]
  • Number of patients with adverse events [ Time Frame: up to 25 weeks ]

Enrollment: 208
Study Start Date: February 2001
Primary Completion Date: February 2002 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: TPV/r low dose

Drug: Tipranavir low dose
Drug: Ritonavir high dose
Experimental: TPV/r medium dose

Drug: Tipranavir medium dose
Drug: Ritonavir low dose
Experimental: TPV/r high dose

Drug: Tipranavir high dose
Drug: Ritonavir low dose
Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 75 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. Signed informed consent prior to trial participation
  2. Between 18 and 75 years of age inclusive
  3. Female subjects of child bearing potential are required to use a barrier contraceptive method for at least 12 weeks prior to administration of study medication, during study medication administration, and for 28 days after the end of the study
  4. Ability to swallow capsules without difficulty
  5. A Body Mass Index (BMI) between 11 and 50 kg/m2
  6. Reasonable probability for completion of the study
  7. Acceptable screening laboratory values. All laboratory values ≤ Grade I (e.g., creatine phosphokinase (CPK), amylase, triglycerides) are permissible if documentation of stability for 2 months or more is available. Abnormalities > Grade I are subject to approval by BI clinical monitor or designee
  8. Acceptable medical history, physical examination, ECG, and chest X-ray prior to entering the treatment phase of the study
  9. Willingness to abstain from alcohol from Day -2 to Day 23
  10. Willingness to abstain from ingesting grapefruit, grapefruit juice, Seville oranges or orange marmalade from Day -2 to Day 23
  11. Negative urine drug screen for drugs of abuse. Subjects on methadone or equivalent narcotic maintenance programs will be permitted to enter the study
  12. Documented HIV-1 RNA load (by PCR) at screening of ≤20,000 copies/mL for at least twelve weeks. Acceptable documentation would include laboratory data, a letter or a verbal report from another provider noted in the subject records.
  13. Stable doses of approved NRTIs and NNRTIs 2 for a minimum of twelve weeks prior to study Day 0. Subjects on efavirenz must be able to tolerate daily morning (8:00 a.m.) dosing starting at screening period and for 22 days of the study. Subjects receiving bid ddI must be willing to accept a change to the once a day delayed release (EC) formulation

  • Exclusion Criteria:
  • Female subjects who:
    • have a positive serum pregnancy test at Screening Period Day -14 to -7
    • are breast feeding
  • Receipt of any other investigational medicine for 30 days prior to Day 0
  • Receipt of any known cytochrome P450 3A4 (CYP3A4) altering drug i.e. phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids and herbal medications for 30 days prior to Day 0. No antibiotics permitted within 10 days prior to Day 0
  • Ingestion of grapefruit, grapefruit juice, Seville oranges or orange marmalade within 2 days of study entry (Day 0)
  • Blood or plasma donations (>100 ml total) for research or altruistic reasons within 30 days prior to Day 0
  • Seated systolic blood pressure either <100 mm Hg or >150 mm Hg; resting heart rate either <50 beats/minute or >90 beats/minute
  • History of any illness, including malabsorption, irregular food intake or gastrointestinal intolerance, or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering TPV/RTV
  • Any acute illness within 2 weeks prior to Day 0
  • Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0, or who are currently taking any prescription drug that, in the opinion of the investigator (in consultation with the BI medical monitor and/or pharmacokineticist), might interfere with either the absorption, distribution or metabolism of the TPV/RTV
  • Hypersensitivity to TPV, RTV or sulfonamide containing drugs
  • Using the adherence diary, subject has less than 100% documented adherence for the last 14 doses (7 days) of baseline antiretroviral medications prior to Day 0. Subjects has less than 100% adherence for the last 7 doses (7 days) of efavirenz and ddI (delayed release) prior to Day 0

    contacts and locations

    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: NCT02251223

    Sponsors and Collaborators

    Boehringer Ingelheim
    More Information

    More Information

    Additional Information:

    Related Info

    Responsible Party: Boehringer Ingelheim  
    ClinicalTrials.gov Identifier: NCT02251223   History of Changes  
    Other Study ID Numbers: 1182.6  
    Study First Received: September 25, 2014  
    Last Updated: September 25, 2014  

    Additional relevant MeSH terms:
    HIV Infections
    Ritonavir
    Tipranavir
    Reverse Transcriptase Inhibitors

    ClinicalTrials.gov processed this data on December 15, 2017
    This information is provided by ClinicalTrials.gov.