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

NCT ID: NCT00076999

Last Updated: 2014-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TPV/r 290/115 mg/m^2

TPV and RTV oral solution low dose

Group Type: EXPERIMENTAL

TPV oral solution

Intervention Type: DRUG

Tipranavir oral solution

RTV oral solution

Intervention Type: DRUG

Ritonavir oral solution

TPV/r 375/150 mg/m^2

TPV and RTV oral solution high dose

Group Type: EXPERIMENTAL

TPV oral solution

Intervention Type: DRUG

Tipranavir oral solution

RTV oral solution

Intervention Type: DRUG

Ritonavir oral solution

Interventions

TPV oral solution

Tipranavir oral solution

Intervention Type: DRUG

TPV oral solution

Tipranavir oral solution

Intervention Type: DRUG

RTV oral solution

Ritonavir oral solution

Intervention Type: DRUG

RTV oral solution

Ritonavir oral solution

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Boehringer Ingelheim

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1182.14.00001 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

1182.14.00006 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

1182.14.00010 Boehringer Ingelheim Investigational Site

Hartford, Connecticut, United States

1182.14.00004 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

1182.14.00008 Boehringer Ingelheim Investigational Site

North Worcester, Massachusetts, United States

1182.14.00009 Boehringer Ingelheim Investigational Site

Springfield, Massachusetts, United States

1182.14.00002 Boehringer Ingelheim Investigational Site

Cleveland, Ohio, United States

1182.14.00007 Boehringer Ingelheim Investigational Site

Memphis, Tennessee, United States

1182.14.00003 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

1182.14.5401 Fundación Huésped

Capital Federal, , Argentina

1182.14.55002

São Paulo, , Brazil

1182.14.55003

São Paulo, , Brazil

1182.14.11002 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

1182.14.11001 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

1182.14.33004 Boehringer Ingelheim Investigational Site

Lyon, , France

1182.14.33005 Boehringer Ingelheim Investigational Site

Nantes, , France

1182.14.33001 Boehringer Ingelheim Investigational Site

Paris, , France

1182.14.33002 Boehringer Ingelheim Investigational Site

Paris, , France

1182.14.33003 Boehringer Ingelheim Investigational Site

Paris, , France

1182.14.33006 Boehringer Ingelheim Investigational Site

Paris, , France

1182.14.49002 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1182.14.49001 Boehringer Ingelheim Investigational Site

Frankfurt am Main, , Germany

1182.14.49004 Boehringer Ingelheim Investigational Site

München, , Germany

1182.14.39001 Boehringer Ingelheim Investigational Site

Padua, , Italy

1182.14.39003 Boehringer Ingelheim Investigational Site

Roma, , Italy

1182.14.52001 CLINDI (Clínica de Inmunodeficiencias)

México, D.F., , Mexico

1182.14.52002

México, D.F., , Mexico

1182.14.00005 Boehringer Ingelheim Investigational Site

San Juan, , Puerto Rico

1182.14.34002 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

1182.14.34001 Boehringer Ingelheim Investigational Site

Madrid, , Spain

Countries

United States; Argentina; Brazil; Canada; France; Germany; Italy; Mexico; Puerto Rico; Spain

References

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.

Reference Type: DERIVED

PMID: 23995585 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 18753862 (View on PubMed)

Other Identifiers

1182.14

Identifier Type: -

Identifier Source: org_study_id