A Pharmacokinetic (PK) Study of a Combination of Indinavir, Ritonavir, and Amprenavir

NCT00148785 | Completed Phase 4

• 3 other identifiers: IRB00006856040082804G
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

When individuals who are infected with HIV are started on treatment with HIV medications, the effect of these drugs only lasts for a limited period of time, often because of development of drug resistance by the HIV virus. When this happens, such patients have to be switched to different combinations of HIV medications. However, since the availability of new HIV drugs that are active against resistant virus is limited, HIV care providers are resorting to curtail medications that contain three or more protease inhibitors (PIs). The reason for this is Norvir (ritonavir), a PI that has the ability to boost or increase the blood levels of other PIs in a way that can sometimes overcome the resistance of HIV virus. In addition, it may be more difficult for the virus to overcome two or more drugs with high blood levels, than it is to overcome just one. For these reasons, many clinicians are now using Norvir in combination with two other PIs, including Crixivan (indinavir) plus Lexiva (fosamprenavir), for treating patients who have been exposed to many other HIV medications. While this may be the case, researchers also know that when two or more PIs are combined, the effects each drug may have on the blood level of other drugs could be different. For example, researchers know from some recent studies that the combination of Norvir, Lexiva, and Kaletra, another PI, leads to an unacceptably low level of both Kaletra and Lexiva. Because researchers can not always assume that when multiple HIV medications are combined, the levels will remain high enough to be effective, the investigators think it will always be reasonable that, before any combination of drugs are used on HIV-infected patients, the effect a combination has on the levels of each of the drugs in the combination should be investigated. AIMS: The aim of this pilot study therefore is to examine the blood levels of Crixivan, Lexiva, and Norvir when these three drugs are used together as part of a combination treatment for HIV infection. METHODS: Fifteen (15) HIV-infected volunteers already being treated with a Crixivan and Norvir containing regimen will be recruited from the Grady Infectious Disease Clinic (IDP). Lexiva will be added to this regimen for 5 days, at the end of which participants will be admitted to the Grady General Clinical Research Center (GCRC) where blood samples will be collected at 9 different time points over 12 hours for measurement of blood drug levels. Pharmacokinetic Analysis: The blood concentrations of Crixivan, Lexiva, and Norvir will be measured by a special technique known as reverse-phase high-performance liquid chromatography with ultraviolet detection. Statistical Analysis: The blood level information will be summarized by a statistical method. The researchers will then compare the levels of Lexiva in this combination with historically published levels of Lexiva in a study of Lexiva plus Norvir; and that of Crixivan in a study of Crixivan plus Norvir. A difference of 30% or more in drug levels between this study and historical reports will be considered a significant difference.

Conditions

HIV Infections

Keywords

Antiretroviral drugs; Pharmacokinetic; Indinavir; Ritonavir; Fosamprenavir

Outcome Measures

Primary Outcomes (1)

• To compare the steady state Cmax, Cmin, AUC0-12h, and the t1/2 of RTV and IDV in HIV-infected patients treated with IDV/RTV 800/100 mg, in the presence and absence of added fos-APV 700 mg twice a day (bid)

Secondary Outcomes (1)

• To evaluate the Cmax, Cmin, AUC0-12h, and the t1/2 APV in a double boosted PI regimen of IDV/fos-APV/RTV 800/700/100 mg bid as compared to historical results of APV pharmacokinetics in a regimen of APV/RTV 700/100 mg bid

Interventions

Indinavir/Ritonavir/Fosamprenavir DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or more
• Diagnosis of HIV infection or AIDS as previously established by HIV ELISA test and confirmed by Western blot analysis
• Must have been taking and tolerating IDV/RTV 800/100 mg bid as part of an antiretroviral regimen.

You may not qualify if:

• Hepatic abnormality: alanine-aminotransferase (ALT), aspartate- aminotransferase (AST) or total bilirubin (TBR) greater than 3x upper limit of normal
• Renal insufficiency: serum creatinine greater than 2 mg/dl
• Co-infection with hepatitis B and/or C viruses
• Pregnant or breastfeeding
• Use of concurrent medications known to affect IDV or APV concentrations significantly (e.g. rifampin, rifabutin, non-nucleoside reverse transcriptase inhibitor \[NNRTI\], other PIs, St John's Wort, herbal preparations)

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Grady Infectious Diseases Program

Atlanta, Georgia, 30308, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Indinavir

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)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Igho Ofotokun, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: July 1, 2005
• Study Completion: January 1, 2007
• Last Updated: November 11, 2013

Record last verified: 2013-11

Locations

US (1)