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

25. april 2014 opdateret af: Boehringer Ingelheim

Multiple-dose, Open-label, Randomized, Safety and Pharmacokinetic Study of Tipranavir in Combination With Low-dose Ritonavir in HIV-infected Pediatric Patients

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

115

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

2 år til 18 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: TPV/r 290/115 mg/m^2
TPV and RTV oral solution low dose
Medicin: TPV oral solution
Tipranavir oral solution
Medicin: RTV oral solution
Ritonavir oral solution
Eksperimentel: TPV/r 375/150 mg/m^2
TPV and RTV oral solution high dose
Medicin: TPV oral solution
Tipranavir oral solution
Medicin: RTV oral solution
Ritonavir oral solution

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Severe (DAIDS Grades 3 or 4) Adverse Events Related to Drug for Treated Patients by Age Group and Formulation
Tidsramme: 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.
up to 288 weeks
Number of Patients With Severe (DAIDS Grades 3 or 4) Laboratory Abnormalities by Age Group and Formulation
Tidsramme: 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.
up to 288 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 24 (Non-completers Considered Failures)
Tidsramme: baseline, week 24
baseline, week 24
Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 48 (Non-completers Considered Failures)
Tidsramme: baseline, week 48
baseline, week 48
Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 100 (Non-completers Considered Failures)
Tidsramme: baseline, week 100
baseline, week 100
Number Patients With HIV RNA <400 Copies/mL at Week 24 (Non-completers Considered Failures)
Tidsramme: baseline, week 24
baseline, week 24
Number Patients With HIV RNA <400 Copies/mL at Week 48 (Non-completers Considered Failures)
Tidsramme: baseline, week 48
baseline, week 48
Number Patients With HIV RNA <400 Copies/mL at Week 100 (Non-completers Considered Failures)
Tidsramme: baseline, week 100
baseline, week 100
Number Patients With HIV RNA <50 Copies/mL at Week 24 (Non-completers Considered Failures)
Tidsramme: baseline, week 24
baseline, week 24
Number Patients With HIV RNA <50 Copies/mL at Week 48 (Non-completers Considered Failures)
Tidsramme: baseline, week 48
baseline, week 48
Number Patients With HIV RNA <50 Copies/mL at Week 100 (Non-completers Considered Failures)
Tidsramme: baseline, week 100
baseline, week 100
Baseline Median Viral Load log10 Copies/mL
Tidsramme: baseline
baseline
Median Change From Baseline in Viral Load log10 Copies/mL at Week 24 (Last Observation Carried Forward)
Tidsramme: baseline, week 24
baseline, week 24
Median Change From Baseline in Viral Load log10 Copies/mL at Week 48 (Last Observation Carried Forward)
Tidsramme: baseline, week 48
baseline, week 48
Median Change From Baseline in Viral Load log10 Copies/mL at Week 100 (Last Observation Carried Forward)
Tidsramme: baseline, week 100
baseline, week 100
Baseline Median CD4+ Cell Count (Cells/mm3)
Tidsramme: baseline
baseline
Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 24 (Last Observation Carried Forward)
Tidsramme: baseline, week 24
baseline, week 24
Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 48 (Last Observation Carried Forward)
Tidsramme: baseline, week 48
baseline, week 48
Median Change From Baseline in CD4+ Cell Count (Cells/mm3) at Week 100 (Last Observation Carried Forward)
Tidsramme: baseline, week 100
baseline, week 100
Median Baseline CD4 Percent
Tidsramme: baseline
Percentage of lymphocytes that are CD4 cells
baseline
Median Change From Baseline in CD4 Percent at Week 24 (Last Observation Carried Forward)
Tidsramme: baseline, week 24
Percentage of lymphocytes that are CD4 cells
baseline, week 24
Median Change From Baseline in CD4 Percent at Week 48 (Last Observation Carried Forward)
Tidsramme: baseline, week 48
Percentage of lymphocytes that are CD4 cells
baseline, week 48
Median Change From Baseline in CD4 Percent at Week 100 (Last Observation Carried Forward)
Tidsramme: baseline, week 100
Percentage of lymphocytes that are CD4 cells
baseline, week 100
Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 8
Tidsramme: week 8
week 8
Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 16
Tidsramme: week 16
week 16
Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 24
Tidsramme: week 24
week 24
Number Patients With Compliance With Tipranavir Treatment Between 95 and 120 Percent at Week 48
Tidsramme: week 48
week 48

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Boehringer Ingelheim

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. november 2003

Primær færdiggørelse (Faktiske)

1. juni 2010

Datoer for studieregistrering

Først indsendt

9. februar 2004

Først indsendt, der opfyldte QC-kriterier

9. februar 2004

Først opslået (Skøn)

10. februar 2004

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

12. maj 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. april 2014

Sidst verificeret

1. april 2014

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 1182.14

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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