Clinical Trials

MainTitle

Pharmacokinetics and Safety Study of Tipranavir in Combination With Low Dose Ritonavir in Human Immunodeficiency Virus (HIV)-Infected Children

This study has been completed
Sponsor
Boehringer Ingelheim


Information provided by (Responsible Party)
Boehringer Ingelheim
ClinicalTrials.gov Identifier
NCT00076999

First received: February 9, 2004
Last updated: April 25, 2014
Last Verified: April 2014
History of Changes
Purpose

Purpose

The primary objective of this study is to assess the safety and tolerability of tipranavir (TPV) oral formulation and soft gelatin capsules together with low-dose ritonavir in HIV-infected children and adolescents, to provide information concerning the pharmacokinetic characteristics of tipranavir and ritonavir in this age group, and to determine the relative bioavailability of the TPV liquid formulation and TPV capsule formulation in adolescents switching from liquid to capsule.

The secondary objective of this study is the determination of the dose of topranavir and ritonavir (TPV/r) in children and adolescents between 2 and 18 years of age required for an adult equivalent systemic exposure of TPV/r 500 mg / 200 mg.

Condition Intervention Phase
HIV Infections

Drug : TPV oral solution
Drug : RTV oral solution
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multiple-dose, Open-label, Randomized, Safety and Pharmacokinetic Study of Tipranavir in Combination With Low-dose Ritonavir in HIV-infected Pediatric Patients

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures

  • Number of Severe (DAIDS Grades 3 or 4) Adverse Events Related to Drug for Treated Patients by Age Group and Formulation [ Time Frame: up to 288 weeks ]
    Intensity of adverse events were graded by the investigator based on the DAIDS standardized table (Division of AIDS, National Institute of Health). DAIDS Grade 3 (Severe) and Grade 4 (Life Threatening) were identified.
  • Number of Patients With Severe (DAIDS Grades 3 or 4) Laboratory Abnormalities by Age Group and Formulation [ Time Frame: up to 288 weeks ]
    Intensity of adverse events were graded by the investigator based on the DAIDS standardized table (Division of AIDS, National Institute of Health). DAIDS Grade 3 (Severe) and Grade 4 (Life Threatening) were identified.
Secondary Outcome Measures:
  • Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 24 (Non-completers Considered Failures) [ Time Frame: baseline, week 24 ]
  • Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ]
  • Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 24 (Non-completers Considered Failures) [ Time Frame: baseline, week 24 ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 24 (Non-completers Considered Failures) [ Time Frame: baseline, week 24 ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ]
  • Baseline Median Viral Load log10 Copies/mL [ Time Frame: baseline ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 24 (Last Observation Carried Forward) [ Time Frame: baseline, week 24 ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 48 (Last Observation Carried Forward) [ Time Frame: baseline, week 48 ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 100 (Last Observation Carried Forward) [ Time Frame: baseline, week 100 ]
  • Baseline Median CD4+ Cell Count (Cells/mm3) [ Time Frame: baseline ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 24 (Last Observation Carried Forward) [ Time Frame: baseline, week 24 ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 48 (Last Observation Carried Forward) [ Time Frame: baseline, week 48 ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 100 (Last Observation Carried Forward) [ Time Frame: baseline, week 100 ]
  • Median Baseline CD4 Percent [ Time Frame: baseline ]
    Percentage of lymphocytes that are CD4 cells
  • Median Change From Baseline in CD4 Percent at Week 24 (Last Observation Carried Forward) [ Time Frame: baseline, week 24 ]
    Percentage of lymphocytes that are CD4 cells
  • Median Change From Baseline in CD4 Percent at Week 48 (Last Observation Carried Forward) [ Time Frame: baseline, week 48 ]
    Percentage of lymphocytes that are CD4 cells
  • Median Change From Baseline in CD4 Percent at Week 100 (Last Observation Carried Forward) [ Time Frame: baseline, week 100 ]
    Percentage of lymphocytes that are CD4 cells
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 8 [ Time Frame: week 8 ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 16 [ Time Frame: week 16 ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 24 [ Time Frame: week 24 ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 48 [ Time Frame: week 48 ]

Enrollment: 115
Study Start Date: November 2003
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: TPV/r 290/115 mg/m^2
TPV and RTV oral solution low dose
Drug: TPV oral solution

Tipranavir oral solution

Drug: RTV oral solution

Ritonavir oral solution

Experimental: TPV/r 375/150 mg/m^2
TPV and RTV oral solution high dose
Drug: TPV oral solution

Tipranavir oral solution

Drug: RTV oral solution

Ritonavir oral solution

Eligibility

Eligibility

Ages Eligible for Study: 2 Years to 18 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion criteria:

    1. Males and females between 2 and 18 years of age.
    2. A confirmed diagnosis of HIV-1 infection as defined by two positive assays from two different samples taken at least two weeks apart. The two results may be any combination of the following:

    HIV ribonucleic acid (RNA) detected by reverse transcriptase (RT)-polymerase chain reaction(PCR) or HIV proviral deoxyribonucleic acid (DNA) detected by PCR HIV culture p24 antigen detection Licensed HIV enzyme-linked immunosorbent assay (ELISA) with confirmatory Western blot
  1. Viral load > 1500 RNA copies/mL.
  2. Acceptable screening laboratory values indicative of adequate baseline organ function. Laboratory values are considered acceptable if severity is no higher than Grade 1 for all tests defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading Severity of Pediatric Adverse Experiences (> 3 months of age) with the following exceptions:

Grade 2 gamma-glutamyl transferase Grade 2 cholesterol Grade 2 triglycerides
  • Signed informed consent prior to study participation from the patient or a legal guardian.

  • Active assent must be given by the patient if the child and/or adolescent is capable of understanding the provided study information (this applies to children with the intellectual age of 7 years or greater)
  • In the opinion of the investigator, an ability to take medications and comply with the requirements of the protocol.


  • Exclusion Criteria:
      1. Female patients of childbearing potential who:

      have a positive serum pregnancy test at screening are breast feeding are planning on becoming pregnant are not willing to use two methods of contraception to include at least one barrier method (e.g. latex condom plus spermicidal jelly/foam)
    1. Active hepatitis B or C disease defined as hepatitis B surface antigen (HBsAg) positivity or hepatitis C (HCV) antibody or RNA positivity with aspartate aminotransferase(AST)/ alanine aminotransferase(ALT) > Grade 2.
    2. Life expectancy < 12 months.
    3. Patients who are unwilling to abstain from ingesting contraindicated medications and substances which may significantly affect plasma levels of the study medications, notably:

    Grapefruit juice or Seville oranges Herbal preparations containing St. John's Wort or milk thistle Garlic supplements
  • Active substance abuse.
  • Use of investigational medications or vaccines within 28 days before study entry or during the trial. Some expanded access antiretroviral medications may be acceptable, but must be approved by sponsor.
  • Requirement for any therapy for malignancy or immunomodulatory drug (e.g. interferon, cyclosporine, hydroxyurea, interleukin-2) within 28 days of study entry. Replacement intravenous gamma globulin treatment is acceptable.
  • Any active opportunistic infection within 28 days before study entry or other clinically significant findings that may compromise the outcome of the study.
  • Patients with malabsorption, severe chronic diarrhea or vomiting (more than two episodes of moderate or severe intensity, not attributed to medication therapy and lasting more than four days) within 28 days of the study.
  • Evidence or symptoms of encephalopathy or developmental delay that would reduce compliance.

    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: NCT00076999

    Locations

    United States, California
    1182.14.00001 Boehringer Ingelheim Investigational Site
    Los Angeles, California, United States
    1182.14.00006 Boehringer Ingelheim Investigational Site
    Los Angeles, California, United States
    United States, Connecticut
    1182.14.00010 Boehringer Ingelheim Investigational Site
    Hartford, Connecticut, United States
    United States, Illinois
    1182.14.00004 Boehringer Ingelheim Investigational Site
    Chicago, Illinois, United States
    United States, Massachusetts
    1182.14.00008 Boehringer Ingelheim Investigational Site
    North Worcester, Massachusetts, United States
    1182.14.00009 Boehringer Ingelheim Investigational Site
    Springfield, Massachusetts, United States
    United States, Ohio
    1182.14.00002 Boehringer Ingelheim Investigational Site
    Cleveland, Ohio, United States
    United States, Tennessee
    1182.14.00007 Boehringer Ingelheim Investigational Site
    Memphis, Tennessee, United States
    United States, Texas
    1182.14.00003 Boehringer Ingelheim Investigational Site
    Houston, Texas, United States
    Argentina
    1182.14.5401 Fundación Huésped
    Capital Federal, Argentina
    Brazil
    1182.14.55002
    São Paulo, Brazil
    1182.14.55003
    São Paulo, Brazil
    Canada
    1182.14.11002 Boehringer Ingelheim Investigational Site
    Toronto, Ontario, Canada
    1182.14.11001 Boehringer Ingelheim Investigational Site
    Montreal, Quebec, Canada
    France
    1182.14.33004 Boehringer Ingelheim Investigational Site
    Lyon cedex 3, France
    1182.14.33005 Boehringer Ingelheim Investigational Site
    Nantes cedex 1, France
    1182.14.33006 Boehringer Ingelheim Investigational Site
    Paris cedex 12, France
    1182.14.33003 Boehringer Ingelheim Investigational Site
    Paris cedex 14, France
    1182.14.33001 Boehringer Ingelheim Investigational Site
    Paris cedex 15, France
    1182.14.33002 Boehringer Ingelheim Investigational Site
    Paris, France
    Germany
    1182.14.49002 Boehringer Ingelheim Investigational Site
    Berlin, Germany
    1182.14.49001 Boehringer Ingelheim Investigational Site
    Frankfurt/Main, Germany
    1182.14.49004 Boehringer Ingelheim Investigational Site
    München, Germany
    Italy
    1182.14.39001 Boehringer Ingelheim Investigational Site
    Padova, Italy
    1182.14.39003 Boehringer Ingelheim Investigational Site
    Roma, Italy
    Mexico
    1182.14.52001 CLINDI (Clínica de Inmunodeficiencias)
    México, D.F., Mexico
    1182.14.52002
    México, D.F., Mexico
    Puerto Rico
    1182.14.00005 Boehringer Ingelheim Investigational Site
    San Juan, Puerto Rico
    Spain
    1182.14.34002 Boehringer Ingelheim Investigational Site
    Barcelona, Spain
    1182.14.34001 Boehringer Ingelheim Investigational Site
    Madrid, Spain

    Sponsors and Collaborators

    Boehringer Ingelheim

    Investigators

    Study Chair: Boehringer Ingelheim Boehringer Ingelheim
    More Information

    More Information


    Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim  
    ClinicalTrials.gov Identifier: NCT00076999   History of Changes  
    Other Study ID Numbers: 1182.14  
    Study First Received: February 9, 2004  
    Last Updated: April 25, 2014  

    Additional relevant MeSH terms:
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Pharmaceutical Solutions
    Ritonavir
    Tipranavir

    ClinicalTrials.gov processed this data on December 18, 2017
    This information is provided by ClinicalTrials.gov.