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Safety and Tolerance of Indinavir Plus Ritonavir in HIV-Positive Patients Failing Therapy With Amprenavir, Nelfinavir, or Saquinavir

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Indinavir sulfate
Ritonavir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Dose-Response Relationship, Drug, Drug Therapy, Combination, HIV Protease Inhibitors, Ritonavir, Indinavir, Anti-HIV Agents, Pharmacokinetics, Treatment Experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Patients may be eligible for this study if they: Are HIV-positive. Are at least 18 years old. Have a viral load (level of HIV in the blood) of at least 500 copies/ml but no more than 100,000 copies/ml within 45 days of study entry. Have been taking the following anti-HIV drug combination for at least 12 weeks before study entry: 2 NRTIs plus amprenavir (APV), nelfinavir (NFV), saquinavir (SQV), or NFV plus SQV. Are naive to at least 1 NRTI. This means that there is at least 1 NRTI that the patient has not taken for more than 14 days. In the case of lamivudine (3TC), naive means that the patient has never taken this drug. Are willing and able to drink 1.5 liters (a little over 1.5 quarts) of water or other fluids a day. Agree to use an effective barrier method of birth control (such as condoms) during the study and for 3 months after. Exclusion Criteria Patients will not be eligible for this study if they: Have taken protease inhibitors other than APV, NFV, SQV, or NFV plus SQV. Are resistant to the effects of IDV or RTV, as shown by a blood test. (Patients whose viral load is between 500 and 1,000 copies/ml will not need to be tested.) Have any active opportunistic (AIDS-related) infection in the 14 days before study entry. Have any medical condition or history of disease that would prevent them from completing the study or put them at risk. Have cancer that requires chemotherapy. Have an active infection that requires treatment in the 14 days before study entry. Have a fever for a week or more in the 30 days before study entry. Have taken nonnucleoside reverse transcriptase inhibitors (NNRTIs) in the 30 days before study entry. Have received a vaccine in the 21 days before study entry. Have received an experimental drug or a drug that affects the immune system in the 30 days before study entry. Have taken or plan to take certain other medications that may affect the study. Are pregnant or breast-feeding.

Sites / Locations

  • Alabama Therapeutics CRS
  • USC CRS
  • Ucsf Aids Crs
  • Johns Hopkins Adult AIDS CRS
  • NY Univ. HIV/AIDS CRS
  • Univ. of Cincinnati CRS
  • Pitt CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
January 17, 2000
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001133
Brief Title
Safety and Tolerance of Indinavir Plus Ritonavir in HIV-Positive Patients Failing Therapy With Amprenavir, Nelfinavir, or Saquinavir
Official Title
A Phase I/II, Randomized, Open-Label Study of the Safety and Pharmacokinetics of Indinavir + Ritonavir Therapy in HIV-Infected Subjects Failing Amprenavir, Nelfinavir, Saquinavir, or Nelfinavir/Saquinavir Combination Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
In this study, the protease inhibitors indinavir (IDV) and ritonavir (RTV) will be studied in patients who have high levels of virus while taking other protease inhibitors. The purpose of this study is to see how the body takes in, distributes, and gets rid of IDV and RTV. This study will also look at any side effects that IDV or RTV causes. IDV is an effective anti-HIV drug, but it can be difficult for patients to take. For IDV to work against HIV, it must be taken 3 times a day at a high dose and with a certain diet. Doctors believe IDV may be easier to take if it is given with RTV. Patients who take IDV and RTV together may be able to take IDV only twice a day and at a lower dose. This study will gather information about the safety and side effects of using IDV and RTV together.
Detailed Description
IDV, a protease inhibitor, has shown excellent clinical and virologic responses when combined with 2 nucleoside analogues. Although effective, the pharmacokinetics of IDV make it difficult to use in many patients. The drug has a short half-life and requires administration in high doses every 8 hours with significant dietary restrictions. Research has shown that IDV kinetics can be improved significantly by the addition of RTV, allowing for administration of IDV at lower doses every 12 hours. The half-life of IDV is prolonged 3- to 5-fold when administered with RTV. Based on these results, it is reasonable to study this combination as a twice-daily dosing regimen. Patients are randomized to receive 1 of 2 doses of IDV/RTV for 24 weeks (Arms A and B). All patients also receive 2 nucleoside reverse transcriptase inhibitors (NRTIs). The NRTIs are not provided by the study. Clinical assessments take place at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 which includes a virology assessment. [AS PER AMENDMENT 4/21/00: Patients who experience a confirmed virologic failure (defined in protocol) and elect to remain on study treatment, are followed through Week 24. Patients who experience a confirmed virologic failure and elect to discontinue study treatment will have a final evaluation at the time of treatment discontinuation.] Patients are hospitalized for 12 hours at the Week 2 study visit for an intensive pharmacokinetic analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Dose-Response Relationship, Drug, Drug Therapy, Combination, HIV Protease Inhibitors, Ritonavir, Indinavir, Anti-HIV Agents, Pharmacokinetics, Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
50 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Indinavir sulfate
Intervention Type
Drug
Intervention Name(s)
Ritonavir

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients may be eligible for this study if they: Are HIV-positive. Are at least 18 years old. Have a viral load (level of HIV in the blood) of at least 500 copies/ml but no more than 100,000 copies/ml within 45 days of study entry. Have been taking the following anti-HIV drug combination for at least 12 weeks before study entry: 2 NRTIs plus amprenavir (APV), nelfinavir (NFV), saquinavir (SQV), or NFV plus SQV. Are naive to at least 1 NRTI. This means that there is at least 1 NRTI that the patient has not taken for more than 14 days. In the case of lamivudine (3TC), naive means that the patient has never taken this drug. Are willing and able to drink 1.5 liters (a little over 1.5 quarts) of water or other fluids a day. Agree to use an effective barrier method of birth control (such as condoms) during the study and for 3 months after. Exclusion Criteria Patients will not be eligible for this study if they: Have taken protease inhibitors other than APV, NFV, SQV, or NFV plus SQV. Are resistant to the effects of IDV or RTV, as shown by a blood test. (Patients whose viral load is between 500 and 1,000 copies/ml will not need to be tested.) Have any active opportunistic (AIDS-related) infection in the 14 days before study entry. Have any medical condition or history of disease that would prevent them from completing the study or put them at risk. Have cancer that requires chemotherapy. Have an active infection that requires treatment in the 14 days before study entry. Have a fever for a week or more in the 30 days before study entry. Have taken nonnucleoside reverse transcriptase inhibitors (NNRTIs) in the 30 days before study entry. Have received a vaccine in the 21 days before study entry. Have received an experimental drug or a drug that affects the immune system in the 30 days before study entry. Have taken or plan to take certain other medications that may affect the study. Are pregnant or breast-feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John G. Gerber
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Edward P. Acosta
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
900331079
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Pitt CRS
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15483465
Citation
Acosta EP, Wu H, Hammer SM, Yu S, Kuritzkes DR, Walawander A, Eron JJ, Fichtenbaum CJ, Pettinelli C, Neath D, Ferguson E, Saah AJ, Gerber JG; Adult AIDS Clinical Trials Group 5055 Protocol Team. Comparison of two indinavir/ritonavir regimens in the treatment of HIV-infected individuals. J Acquir Immune Defic Syndr. 2004 Nov 1;37(3):1358-66. doi: 10.1097/00126334-200411010-00004.
Results Reference
result
PubMed Identifier
15958837
Citation
King JR, Gerber JG, Fletcher CV, Bushman L, Acosta EP. Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy. AIDS. 2005 Jul 1;19(10):1059-63. doi: 10.1097/01.aids.0000174452.78497.54.
Results Reference
result
PubMed Identifier
16583266
Citation
Wu H, Huang Y, Acosta EP, Park JG, Yu S, Rosenkranz SL, Kuritzkes DR, Eron JJ, Perelson AS, Gerber JG. Pharmacodynamics of antiretroviral agents in HIV-1 infected patients: using viral dynamic models that incorporate drug susceptibility and adherence. J Pharmacokinet Pharmacodyn. 2006 Aug;33(4):399-419. doi: 10.1007/s10928-006-9006-4. Epub 2006 Apr 1.
Results Reference
result

Learn more about this trial

Safety and Tolerance of Indinavir Plus Ritonavir in HIV-Positive Patients Failing Therapy With Amprenavir, Nelfinavir, or Saquinavir

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