Antiretroviral Drug Interaction Study in Volunteers With HIV

NCT01479361 | Completed Phase 1

• 2 other identifiers: 12001712-CC-0017
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; PCP; Toxoplasmosis

Keywords

Atovaquone; Drug Interaction; Pharmacokinetics; Efavirenz; Atazanavir-Ritonavir; HIV

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to determine the steady state pharmacokinetics of 2 doses of atovaquone oral suspension in the presence of ATV/r, EFV, or no ARVs in HIV-infected patients.

Secondary Outcomes (1)

• To compare our PK results with the recently reported interaction between a single dose of atovaquone+proguanil and ATV/r and EFV, and the comparator group which consists of HIV-infected subjects, as opposed to a comparator group of healthy subje...

Interventions

Atovaquone 750 mg twice daily DRUG

Atovaquone 1500 mg twice daily DRUG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject will be considered eligible for this study only if all of the following criteria are met:
• Between the ages of 18 and 70 years.
• HIV-infected patients stabilized (greater than or equal to 90 days) on ARV regimens containing efavirenz 600 mg daily, or atazanavir/ritonavir 300/100 mg daily or HIV-infected patients not receiving ARV therapy.
• CD4 cells greater than or equal to 350 cells/mm3 for HIV-infected patients not receiving ARV therapy.
• CD4 cells \>200 cells/mm3 for HIV-infected patients receiving ARV therapy.
• Virologically suppressed patients receiving ARV therapy (\<200 copies/mL on at least 2 consecutive occasions, within 6 months prior to enrollment).
• Females of child bearing potential who are able and willing to prevent pregnancy by (a) practicing abstinence or (b) using effective methods of birth control, such as condoms, during the study period and for 1 month after study completion.
• Subject agrees to storage of specimens for future research.

You may not qualify if:

• A subject will be ineligible for this study if 1 or more of the following criteria are met:
• Concomitant routine therapy with any prescription, over-the- counter, herbal, or holistic medications that are known or suspected to alter atovaquone including rifampin, rifabutin, and metoclopramide for 14 days prior to study participation.
• Subjects receiving primary or secondary prophylaxis for PCP or toxoplasmosis.
• ARV regimens containing both EFV and ATV/r.
• Subjects receiving hormonal contraceptives within 90 days of Study Day 1.
• Inability to obtain venous access for sample collection.
• Laboratory and/or physical evidence of any active opportunistic infection.
• Diabetes mellitus requiring treatment with insulin, active tuberculosis, cardiac disease (uncontrolled hypertension and/or heart failure etc.), renal disease (chronic or acute renal failure or insufficiency resulting in baseline serum creatinine greater than 1.5 times upper limit of normal \[ULN\]), untreated/uncontrolled thyroid disease, untreated/uncontrolled psychiatric disease, active hepatitis (liver failure resulting in liver function tests greater than 3 times the ULN, ascites, or jaundice in the absence of ATV), or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the Investigator.
• Positive pregnancy test or breastfeeding female.
• The presence of persistent diarrhea or malabsorption that could interfere with the subject s ability to absorb drugs.
• Drug or alcohol use that may impair safety or adherence.
• History of intolerance or allergic reaction (rash; hives; swollen lips; difficulty breathing) to atovaquone.
• Bleeding disorders (hemophilia, G.I., or intracranial bleeding).
• Organ transplant recipient.
• Documented ongoing problems with medication adherence.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics. 1978 Jan;61(1):35-41.

  PMID: 400818 BACKGROUND

• Hughes WT, Feldman S, Chaudhary SC, Ossi MJ, Cox F, Sanyal SK. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr. 1978 Feb;92(2):285-91. doi: 10.1016/s0022-3476(78)80028-6.

  PMID: 304478 BACKGROUND

• Winston DJ, Lau WK, Gale RP, Young LS. Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia. Ann Intern Med. 1980 Jun;92(6):762-9. doi: 10.7326/0003-4819-92-6-762.

  PMID: 6966901 BACKGROUND

• Calderon MM, Penzak SR, Pau AK, Kumar P, McManus M, Alfaro RM, Kovacs JA. Efavirenz but Not Atazanavir/Ritonavir Significantly Reduces Atovaquone Concentrations in HIV-Infected Subjects. Clin Infect Dis. 2016 Apr 15;62(8):1036-1042. doi: 10.1093/cid/ciw028. Epub 2016 Jan 20.

  PMID: 26797214 DERIVED

MeSH Terms

Conditions

Toxoplasmosis

Interventions

Atovaquone

Condition Hierarchy (Ancestors)

Coccidiosis; Protozoan Infections; Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Naphthoquinones; Quinones; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Joseph A Kovacs, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2011
• First Posted: November 24, 2011
• Study Start: October 31, 2011
• Primary Completion: February 20, 2014
• Study Completion: February 20, 2014
• Last Updated: July 5, 2018

Record last verified: 2016-06-01

Locations

US (1)