Clinical trial NCT00034866: Dose Ranging Trial of Tipranavir/Ritonavir in Treatment-Experienced HIV Infected Individuals
Official title: Double-Blind, Randomized, Dose Optimization Trial of Three Doses of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) in Multiple Antiretroviral Drug-Experienced Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
treatment experienced
Boehringer
tipranavir
ritonavir
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2002-05-03
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine which of three different dose combinations of tipranavir and ritonavir, when taken with a standard approved anti-HIV drug therapy, is most effective and safe. Tipranavir is an investigational protease inhibitor which has been demonstrated to have in vitro activity against HIV-1.

Detailed description: This study will be conducted in HIV+, multiple ARV medication experienced patients. All patients must have received treatment from each of three ARV classes: NRTIs, NNRTIs and PIs, have received at least two PI-based ARV regimens (may include the current regimen) with a viral load greater than or equal to 1000 copies/mL at the time of study entry. The two separate PI-based regimens must each have been taken for at least 3 months. At least one resistance-conferring PI-mutation (from a pre-established panel) must be present. Baseline genotypic screening will be performed and will be used in conjunction with ARV medication history to determine new background therapy for each individual subject to use.

Following genotypic screening at baseline, qualifying subjects will be randomized to one of three blinded treatment regimens. Subjects will discontinue their current protease inhibitor and initiate TPV/RTV for 2 weeks of functional monotherapy. Thereafter, the background ARV medications will be optimized and subjects will remain on blinded TPV/RTV plus optimized background therapy for the duration of the trial. Trial duration ranges between 12-32 weeks, depending on when the subject is entered into the trial and the interim analyses for determination of optimized TPV/RTV regimen is completed. On determination of the optimal TPV/RTV dose, subjects may opt to continue open-label treatment.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent prior to trial participation.
2. HIV-1 infected males or females \>= 18 years of age.
3. At least 3 months experience taking NRTIs, NNRTI(s), and PIs.
4. Current PI-based ARV medication regimen for at least 3 months prior to randomization, and at least 3 months experience taking at least one other PI-based regimen.
5. HIV-1 viral load \>= 1000 copies/mL at screening.
6. Genotypic resistance report indicating one or more primary PI resistance mutation(s), including 30N, 46I/L, 48V, 50V, 82A/F/T, 84V or 90M, with not more than one of 82 A/F/T or 84V or 90M.
7. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if severity is no higher than Grade 3 GGT, Grade 2 cholesterol or triglycerides, and no higher than Grade 1 for all other tests based on the DAIDS Grading Scale. All laboratory values outside these limits are subject to approval by BI.
8. Acceptable medical history, as assessed by the investigator, with chest X-ray and ECG within 1 year of study participation.
9. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system, such as: grapefruit or Seville oranges or their products; herbal preparations containing St. John's Wort or milk thistle, and garlic supplements.
10. A prior AIDS defining event is acceptable as long as it has resolved or the subject has been on stable treatment for at least 2 months.

Exclusion Criteria:

1. ARV medication naïve.
2. Female subjects who:

   * have a positive serum pregnancy test at screening or during the study
   * are breast feeding
   * are planning to become pregnant
   * are not willing to use two barrier methods of contraception (e.g. latex condom plus spermicidal jelly/foam).
3. Any active opportunistic infection within 60 days before study entry.
4. Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT \>Grade 1.
5. Prior tipranavir use.
6. Use of investigational medications within 30 days before study entry or during the trial. Some expanded access drugs may be acceptable; must be approved by BI. Tenofovir, investigational at time of preparation of this protocol, is acceptable.
7. Use of concomitant drugs which may significantly reduce plasma levels of the study medications.
8. Use of immunomodulatory drugs (e.g. interferon, cyclosporin, hydroxyurea, interleukin-2).
9. Active substance abuse.
10. Inability to swallow TPV or RTV capsules.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Body Positive
state: Arizona
city: Fountain Valley
country: United States
facility: Orange County Center for Special Immunology
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Trials Inc.
state: California
city: Los Angeles
country: United States
facility: AHF Research Center
state: California
city: Los Angeles
country: United States
facility: University of So. California / LA County USC Medical Center
state: California
city: Los Angeles
country: United States
facility: ID Care, Inc.
state: California
city: Los Angeles
country: United States
facility: Tower I.D. Medical Assoc., Inc.
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Positive Health Program Research
state: California
city: San Francisco
country: United States
facility: Pacific Horizon Medial Group
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Altamonte Springs
country: United States
facility: (IDC) Research Institute
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Miami
country: United States
facility: Jackson Medical Tower
state: Florida
city: South Miami
country: United States
facility: Steinhart Medical Associates
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Dept.
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center, Dept. of ID
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: CORE Center, Cook County Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian/St. Luke's Medical Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: HIV Outpatient Program (H.O.P.)
state: Louisiana
city: Baltimore
country: United States
facility: John's Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Springfield
country: United States
facility: CRI Community Research Initiative
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital, Infectious Diseases Dept.
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Free Health Clinic
state: Missouri
city: St. Louis
country: United States
facility: Washington University AIDS Clinical Trial Unit
state: Missouri
city: Las Vegas
country: United States
facility: Wellness Center
state: Nevada
city: Hillsborough
country: United States
facility: ID Care, Inc.
state: New Jersey
city: Randolph
country: United States
facility: ID Care, Inc.
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Stony Brook
country: United States
facility: University of New York at Stony Brook
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center Infectious Diseases Clinic
state: North Carolina
city: Huntersville
country: United States
facility: Jemsek Clinic
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Infect. Disease Institute, Clinical Trials Unit
state: Oklahoma
city: Columbia
country: United States
facility: Burnside Clinic
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University - AIDS Clinical Trial Unit
state: Tennessee
city: Dallas
country: United States
facility: Nelson-Tebedo Clinic
state: Texas
city: Houston
country: United States
facility: Gathe Clinic
state: Texas
city: Annandale
country: United States
facility: Infectious Disease Physicians Research
state: Virginia
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
References: