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:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00076999
First received: February 9, 2004
Last updated: April 25, 2014
Last verified: April 2014
  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
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ] [ Designated as safety issue: No ]
  • Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 24 (Non-completers Considered Failures) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <400 Copies/mL at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 24 (Non-completers Considered Failures) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 48 (Non-completers Considered Failures) [ Time Frame: baseline, week 48 ] [ Designated as safety issue: No ]
  • Number Patients With HIV RNA <50 Copies/mL at Week 100 (Non-completers Considered Failures) [ Time Frame: baseline, week 100 ] [ Designated as safety issue: No ]
  • Baseline Median Viral Load log10 Copies/mL [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 24 (Last Observation Carried Forward) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 48 (Last Observation Carried Forward) [ Time Frame: baseline, week 48 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load log10 Copies/mL at Week 100 (Last Observation Carried Forward) [ Time Frame: baseline, week 100 ] [ Designated as safety issue: No ]
  • Baseline Median CD4+ Cell Count (Cells/mm3) [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 24 (Last Observation Carried Forward) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 48 (Last Observation Carried Forward) [ Time Frame: baseline, week 48 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 100 (Last Observation Carried Forward) [ Time Frame: baseline, week 100 ] [ Designated as safety issue: No ]
  • Median Baseline CD4 Percent [ Time Frame: baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 16 [ Time Frame: week 16 ] [ Designated as safety issue: No ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 48 [ Time Frame: week 48 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
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

  3. Viral load > 1500 RNA copies/mL.
  4. 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

  5. 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)

  6. 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)

  2. 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.
  3. Life expectancy < 12 months.
  4. 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

  5. Active substance abuse.
  6. 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.
  7. 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.
  8. Any active opportunistic infection within 28 days before study entry or other clinically significant findings that may compromise the outcome of the study.
  9. 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.
  10. Evidence or symptoms of encephalopathy or developmental delay that would reduce compliance.
  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

  Show 30 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: June 27, 2011
Last Updated: April 25, 2014
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Brazil: Ministry of Health
Canada: Health Canada
France: Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS)
Germany: Federal Institute for Drugs and Medical Devices
Italy: COMITATO ETICO PER LA SPERIMENTAZIONE DELL'AZ. OSP. DI PADOVA
Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)
Spain: Spanish Agency of Medicines
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 20, 2014