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

NCT00076999 | Completed Phase 1 Results

• 1 other identifier: 1182.14
• Study Type: interventional
• Target: 115
• Locations: 10 countries
• Sites: 30

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Number of Severe (DAIDS Grades 3 or 4) Adverse Events Related to Drug for Treated Patients by Age Group and Formulation

  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

  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

Secondary Outcomes (25)

• Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 24 (Non-completers Considered Failures)

  baseline, week 24

• Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 48 (Non-completers Considered Failures)

  baseline, week 48

• Number Patients With at Least 1 log10 Viral Load Reduction From Baseline at Week 100 (Non-completers Considered Failures)

  baseline, week 100

• Number Patients With HIV RNA <400 Copies/mL at Week 24 (Non-completers Considered Failures)

  baseline, week 24

• Number Patients With HIV RNA <400 Copies/mL at Week 48 (Non-completers Considered Failures)

  baseline, week 48

Study Arms (2)

TPV/r 290/115 mg/m^2

EXPERIMENTAL

TPV and RTV oral solution low dose

Drug: TPV oral solution; Drug: RTV oral solution

TPV/r 375/150 mg/m^2

EXPERIMENTAL

TPV and RTV oral solution high dose

Drug: TPV oral solution; Drug: RTV oral solution

Interventions

TPV oral solution DRUG

Tipranavir oral solution

TPV/r 290/115 mg/m^2

RTV oral solution DRUG

Ritonavir oral solution

TPV/r 290/115 mg/m^2

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females between 2 and 18 years of age.
• 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
• Viral load \> 1500 RNA copies/mL.
• 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.

You may not qualify if:

• 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)
• 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.
• Life expectancy \< 12 months.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (30)

1182.14.00001 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1182.14.00006 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1182.14.00010 Boehringer Ingelheim Investigational Site

Hartford, Connecticut, United States

Location

1182.14.00004 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1182.14.00008 Boehringer Ingelheim Investigational Site

North Worcester, Massachusetts, United States

Location

1182.14.00009 Boehringer Ingelheim Investigational Site

Springfield, Massachusetts, United States

Location

1182.14.00002 Boehringer Ingelheim Investigational Site

Cleveland, Ohio, United States

Location

1182.14.00007 Boehringer Ingelheim Investigational Site

Memphis, Tennessee, United States

Location

1182.14.00003 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1182.14.5401 Fundación Huésped

Capital Federal, Argentina

Location

1182.14.55002

São Paulo, Brazil

Location

1182.14.55003

São Paulo, Brazil

Location

1182.14.11002 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1182.14.11001 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1182.14.33004 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1182.14.33005 Boehringer Ingelheim Investigational Site

Nantes, France

Location

1182.14.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.14.33002 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.14.33003 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.14.33006 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.14.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1182.14.49001 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1182.14.49004 Boehringer Ingelheim Investigational Site

München, Germany

Location

1182.14.39001 Boehringer Ingelheim Investigational Site

Padua, Italy

Location

1182.14.39003 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1182.14.52001 CLINDI (Clínica de Inmunodeficiencias)

México, D.F., Mexico

Location

1182.14.52002

México, D.F., Mexico

Location

1182.14.00005 Boehringer Ingelheim Investigational Site

San Juan, Puerto Rico

Location

1182.14.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1182.14.34001 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

Related Publications (2)

• Salazar JC, Cahn P, Della Negra M, De Aquino MZ, Robinson PA, Jelaska A, Mikl J. Efficacy and safety of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents: 5 years of experience. Pediatr Infect Dis J. 2014 Apr;33(4):396-400. doi: 10.1097/INF.0000000000000038.

  PMID: 23995585 DERIVED

• Salazar JC, Cahn P, Yogev R, Negra MD, Castelli-Gattinara G, Fortuny C, Flynn PM, Giaquinto C, Ruan PK, Smith ME, Mikl J, Jelaska A; PACTG 1051/BI Study Team. Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents. AIDS. 2008 Sep 12;22(14):1789-98. doi: 10.1097/QAD.0b013e32830c481b.

  PMID: 18753862 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 9, 2004
• First Posted: February 10, 2004
• Study Start: November 1, 2003
• Primary Completion: June 1, 2010
• Last Updated: May 12, 2014
• Results First Posted: July 25, 2011

Record last verified: 2014-04

Locations

FR (6); ES (2); BR (2); US (9); AR (1); CA (2); ME (2); IT (2); DE (3); PR (1)