Ignite Creation Date:
2025-12-24 @ 1:10 PM
Ignite Modification Date:
2025-12-29 @ 5:43 PM
Study NCT ID:
NCT01479361
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2011-11-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Antiretroviral Drug Interaction Study in Volunteers With HIV
Sponsor:
National Institutes of Health Clinical Center (CC)
Organization:
Study Overview
Official Title:
The Influence of Atazanavir-ritonavir and Efavirenz on Atovaquone Pharmacokinetics in HIV-infected Volunteers
Status:
COMPLETED
Status Verified Date:
2016-06-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
\- People who are infected with the human immunodeficiency virus (HIV) are at risk of getting certain diseases. Two of these diseases are a type of pneumonia known as PCP and a brain infection called toxoplasmosis. Most people with HIV take antiretroviral (ARV) drugs to treat HIV and lower the risk of infections. However, some ARV drugs may make other drugs used to treat PCP and toxoplasmosis less effective. Researchers want to test specific ARV drugs to see if they affect atovaquone, a drug used to treat PCP and toxoplasmosis.
Objectives:
\- To see if ARV drugs atazanavir-ritonavir or efavirenz lower the blood levels of atovaquone.
Eligibility:
* Individuals between 18 and 70 years of age who have HIV.
* Participants must be taking efavirenz or atazanavir-ritonavir, or not taking any ARV drugs.
Design:
* Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
* This study has a screening visit and five study visits. Two of the study visits will last about 12 hours; the other three visits will last about 1 hour each.
* Participants will receive either a low dose or high dose of atovaquone to take for 14 days. They will record doses and any symptoms on a diary card at home.
* After 14 days, participants will have a 12-hour visit to provide blood samples. There will be a wash-out period with no doses for up to 6 weeks.
* After the wash-out period, participants will switch dose levels to either the high or low dose.
* After 14 days, participants will have a 12-hour visit to provide blood samples.
\- People who are infected with the human immunodeficiency virus (HIV) are at risk of getting certain diseases. Two of these diseases are a type of pneumonia known as PCP and a brain infection called toxoplasmosis. Most people with HIV take antiretroviral (ARV) drugs to treat HIV and lower the risk of infections. However, some ARV drugs may make other drugs used to treat PCP and toxoplasmosis less effective. Researchers want to test specific ARV drugs to see if they affect atovaquone, a drug used to treat PCP and toxoplasmosis.
Objectives:
\- To see if ARV drugs atazanavir-ritonavir or efavirenz lower the blood levels of atovaquone.
Eligibility:
* Individuals between 18 and 70 years of age who have HIV.
* Participants must be taking efavirenz or atazanavir-ritonavir, or not taking any ARV drugs.
Design:
* Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
* This study has a screening visit and five study visits. Two of the study visits will last about 12 hours; the other three visits will last about 1 hour each.
* Participants will receive either a low dose or high dose of atovaquone to take for 14 days. They will record doses and any symptoms on a diary card at home.
* After 14 days, participants will have a 12-hour visit to provide blood samples. There will be a wash-out period with no doses for up to 6 weeks.
* After the wash-out period, participants will switch dose levels to either the high or low dose.
* After 14 days, participants will have a 12-hour visit to provide blood samples.
Detailed Description:
The incidence of opportunistic infections such as Pneumocystis jirovecii pneumonia (PCP) and Toxoplasma gondii have substantially declined in patients with HIV infection due to potent combination antiretroviral (ARV) therapy and effective prophylaxis. The drug of choice for prophylaxis and treatment of PCP and toxoplasmosis is trimethoprim-sulfamethoxazole (TMP-SMX) and sulfadiazine, respectively. In patients who cannot tolerate these first line therapies, atovaquone is a common alternative. While generally considered safe and effective, a recent drug interaction study involving a single dose of combination tablet of atovaquone/proguanil (Malarone ) in HIV-infected patients showed that atovaquone plasma concentrations were significantly lowered (compared to healthy volunteers) by 75%, 74%, and 46% in patients taking the ARV medications efavirenz (EFV), lopinavir-ritonavir (LPV/r), and atazanavir-ritonavir (ATV/r), respectively. The mechanism of this drug interaction is unknown but is presumably due to induction of uridine diphosphate glucuronsosyltransferase (UGT) enzymes responsible for the metabolism of atovaquone. The magnitude of this interaction is such that it strongly suggests a clinically relevant drug interaction between atovaquone and the aforementioned ARVs. The purpose of this study is to determine whether HIV-infected subjects receiving ATV/r or EFV-containing ARV regimens, experience reductions in atovaquone exposure under steady state conditions compared to HIV-infected patients not receiving ARV therapy.
In this open-label study, 30 HIV-infected subjects will participate in 1 of 3 groups of 10 (Groups A, B, and C). Group A will consist of 10 subjects who are already receiving combination ARV therapy containing ATV/r; Group B will consist of 10 subjects already receiving combination ARV therapy containing EFV; and Group C will consist of 10 subjects who are not currently receiving ARV therapy. All subjects in Groups A, B, and C will be randomly assigned to either receive atovaquone 750 mg twice daily for 14 days (Phase 1) followed by a 2-6 week washout period, followed by atovaquone 1500 mg twice daily for 14 days (Phase 2), or vice versa. Pharmacokinetic (PK) sampling for atovaquone will occur on Day 14 of Phase 1 and 2.
Atovaquone PK parameters will be determined using non-compartmental methods with the WinNonlin professional computer program (version 5.2; Pharsight Corporation, Mountain View, CA). The following PK parameters will be compared among the groups: area under the concentration vs. time curve (AUC ?), maximum concentration (Cmax), apparent oral clearance (Cl/F), time to reach maximum concentration (Tmax), and half-life (T (Omega)). Data from this investigation will determine whether ATV/r and/or EFV alter the steady state PK of atovaquone in HIV-infected subjects. This information will assist clinicians in choosing appropriate alternative therapies for the treatment of PCP and toxoplasmosis in patients who are not candidates for first line therapies.
In this open-label study, 30 HIV-infected subjects will participate in 1 of 3 groups of 10 (Groups A, B, and C). Group A will consist of 10 subjects who are already receiving combination ARV therapy containing ATV/r; Group B will consist of 10 subjects already receiving combination ARV therapy containing EFV; and Group C will consist of 10 subjects who are not currently receiving ARV therapy. All subjects in Groups A, B, and C will be randomly assigned to either receive atovaquone 750 mg twice daily for 14 days (Phase 1) followed by a 2-6 week washout period, followed by atovaquone 1500 mg twice daily for 14 days (Phase 2), or vice versa. Pharmacokinetic (PK) sampling for atovaquone will occur on Day 14 of Phase 1 and 2.
Atovaquone PK parameters will be determined using non-compartmental methods with the WinNonlin professional computer program (version 5.2; Pharsight Corporation, Mountain View, CA). The following PK parameters will be compared among the groups: area under the concentration vs. time curve (AUC ?), maximum concentration (Cmax), apparent oral clearance (Cl/F), time to reach maximum concentration (Tmax), and half-life (T (Omega)). Data from this investigation will determine whether ATV/r and/or EFV alter the steady state PK of atovaquone in HIV-infected subjects. This information will assist clinicians in choosing appropriate alternative therapies for the treatment of PCP and toxoplasmosis in patients who are not candidates for first line therapies.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 12-CC-0017 | None | None | View |