HIV InfectionPhase 4NCT00054743
Differences in Blood Levels of Nevirapine in HIV-infected Patients in Uganda and the United States
A Phase 4 study testing Blood draw in people with HIV Infection, run by National Institutes of Health Clinical Center (CC) at 2 sites in 2 countries.
Trial summary
This study will determine whether blood levels of the anti-HIV medicine nevirapine are different in HIV-infected patients in the United States from patients in Uganda. People from all over the world take medications to treat HIV infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Blood draw
- Type of treatment
- Surgery or procedure
- How many people
- 24 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 6 Feb 2003to 28 Apr 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documentation in the patient's medical record of HIV-1 infection using double ELISA or a second confirmatory test (e.g., Western Blot) or any one of the following: detectable p24 antigen, quantifiable plasma HIV RNA, or detectable proviral DNA.
- Males and females greater than or equal to 18 years of age
- Laboratory values within acceptable limits
- AST/SGOT less than or equal to 5 times the upper limit of normal (ULN)
- Serum creatinine less than or equal to 2 times the ULN
- Hemoglobin greater than or equal to 9.0 g/dL
- Receipt of a stable nevirapine-containing antiretroviral regimen for at least 28 days.
- Informed consent signed and subject declares that they have been adherent to their nevirapine-containing antiretroviral regimen.
Who cannot join
- Presence of life-threatening or unstable renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or respiratory disease, as determined by medical records, 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.
- Laboratory values outside acceptable limits
- AST/SGOT less than 5 times the upper limit of normal (ULN)
- Serum creatinine greater than 2 times the ULN
- Hemoglobin less than 9.0 g/dL
- Positive pregnancy test.
Show all 14Show fewer
- Receipt of IL-2 within 3 months of study participation.
- Drug or alcohol use that may impair safety or adherence.
- Poor venous access.
- Documented or reported fever (greater than 38.5 degrees C) within 7 days of screening.
- Active opportunistic infection requiring therapy.
- Refusal to agree to allow for specimens to be stored for future research.
- Greater than 4 loose/soft stools per day.
- Subject is non-adherent with their nevirapine-containing antiretroviral regimen and/or they have not provided informed consent.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Global Initiative to Characterize Differences in Antiretroviral Pharmacokinetics in HIV-Infected Populations
This study will determine whether blood levels of the anti-HIV medicine nevirapine are different in HIV-infected patients in the United States from patients in Uganda. People from all over the world take medications to treat HIV infection. These medicines work well in some people but not in others, and they cause harmful side effects in some people and not in others. These differences may be related to variations in how much of the drug reaches the blood. Differences in drug blood levels among people in various areas of the world may be attributed to differences in diet, state of health, ability to absorb the medicines from the stomach, ability to eliminate the drugs from the body, and the brand of medicine taken. This study will help scientists learn whether differences in blood levels of HIV medicines are important in determining how well the drugs work in different patient populations.
HIV-infected patients 18 years of age and older in the United States and in Kampala, Uganda who have been on an antiretroviral treatment regimen that includes at least 28 consecutive days of nevirapine may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood tests.
Read more
Participants will have a total of approximately about 5 ounces of blood drawn during this 6- to 8-hour study. They will come to the NIH clinic in the morning, and a catheter (plastic tube) will be inserted into an arm vein for collecting blood. (Alternatively, blood can be collected by a needle inserted into an arm vein.) Blood will be withdrawn according to the following schedule:
- About 5 tablespoons will be collected upon arrival at the clinic after an overnight fast. Within 30 minutes of this blood draw, the patient will have breakfast and take his or her morning dose of nevirapine, along with any other medications that need to be taken at that time.
- 1 tablespoon of blood will be drawn 2 hours after the nevirapine dose.
- 1 tablespoon of blood will be drawn 4 hours later (6 hours after the nevirapine dose).
The blood will be analyzed for levels of nevirapine and possibly other HIV medicines. Some of the blood will be stored for later analysis of genes (cytochrome P450 and MDR1) that are involved in eliminating medicines from the body.
...
Read the detailed description
The overwhelming majority of HIV-infected persons reside in the developing world. As such, recent efforts have focused on providing antiretroviral pharmacotherapy to this population. However, there are a number of factors indigenous to non-Western HIV-infected patients that may alter their virologic, immunologic, and/or toxicologic response to antiretroviral therapy. Absorption, distribution, and clearance of antiretroviral medications may differ among patients residing in non-Western countries secondary to dietary influences, parasitic infection, and malabsorption. Genetic polymorphisms of drug metabolizing enzymes (cytochrome P450; CYP) and drug transporters (i.e. P-glycoprotein) may also contribute to altered pharmacokinetics among these patients. The purpose of this pilot, hypothesis-generating study is (1) to characterize the pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor nevirapine in a non-Western HIV-infected population (Kampala, Uganda) and in a similar cohort of HIV-infected individuals in the United States and (2) to compare pharmacokinetic parameter values between the groups. Twenty-five subjects from each site will participate. Subjects from the Ugandan site may participate regardless of their CD4+ lymphocyte count and viral load; they will be studied prior to the U.S. cohort. The U.S. group will be selected to include subjects that are matched by gender to their Ugandan counterparts. Subjects will have one pre-dose and two post-dose blood samples collected for the determination of nevirapine plasma concentrations. Samples will be analyzed using LC/MS-MS. Population pharmacokinetics parameter values (Cmax, Cmin, AUC, CL/F, Vd) will be determined using NONMEM(Trademark) and compared between groups. Blood samples collected during the study will also be used to determine CYP and MDR1 genotypes of study subjects in an effort to explain any observed differences in pharmacokinetics parameter values between the study populations.
- Conditions
- HIV Infection
- Being tested
- Blood draw
- Keywords
- Race, Ethnicity, Pharmacogenetics, Cytochrome P450, Population Pharmacokinetics, HIV
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2003 (estimated)
- Study start6 Feb 2003
- Study completion28 Apr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00054743
- Sponsor's protocol ID
- 030091
- Other IDs
- 03-CC-0091
- Status last verified
- 28 Apr 2011
- First submitted
- 7 Feb 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med. 1995 Dec 7;333(23):1528-33. doi: 10.1056/NEJM199512073332303.
PubMed 7477167Harris M, Durakovic C, Rae S, Raboud J, Fransen S, Shillington A, Conway B, Montaner JS. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis. 1998 Jun;177(6):1514-20. doi: 10.1086/515317.
PubMed 9607828Hoetelmans RM, Reijers MH, Weverling GJ, ten Kate RW, Wit FW, Mulder JW, Weigel HM, Frissen PH, Roos M, Jurriaans S, Schuitemaker H, de Wolf F, Beijnen JH, Lange JM. The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy. AIDS. 1998 Jul 30;12(11):F111-5. doi: 10.1097/00002030-199811000-00002.
PubMed 9708400
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Global Initiative to Characterize Differences in Antiretroviral Pharmacokinetics in HIV-Infected Populations
- ClinicalTrials.gov ID
- NCT00054743
- Acronym / sponsor ID
- 030091
- Conditions
- HIV Infection
- Keywords
- Race, Ethnicity, Pharmacogenetics, Cytochrome P450, Population Pharmacokinetics, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 6 Feb 2003
- Study completion
- 28 Apr 2011 (actual)
- First posted
- 10 Feb 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine whether blood levels of the anti-HIV medicine nevirapine are different in HIV-infected patients in the United States from patients in Uganda. People from all over the world take medications to treat HIV infection. These medicines work well in some people but not in others, and they cause harmful side effects in some people and not in others. These differences may be related to variations in how much of the drug reaches the blood. Differences in drug blood levels among people in various areas of the world may be attributed to differences in diet, state of health, ability to absorb the medicines from the stomach, ability to eliminate the drugs from the body, and the brand of medicine taken. This study will help scientists learn whether differences in blood levels of HIV medicines are important in determining how well the drugs work in different patient populations.
HIV-infected patients 18 years of age and older in the United States and in Kampala, Uganda who have been on an antiretroviral treatment regimen that includes at least 28 consecutive days of nevirapine may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood tests.
Participants will have a total of approximately about 5 ounces of blood drawn during this 6- to 8-hour study. They will come to the NIH clinic in the morning, and a catheter (plastic tube) will be inserted into an arm vein for collecting blood. (Alternatively, blood can be collected by a needle inserted into an arm vein.) Blood will be withdrawn according to the following schedule:
- About 5 tablespoons will be collected upon arrival at the clinic after an overnight fast. Within 30 minutes of this blood draw, the patient will have breakfast and take his or her morning dose of nevirapine, along with any other medications that need to be taken at that time.
- 1 tablespoon of blood will be drawn 2 hours after the nevirapine dose.
- 1 tablespoon of blood will be drawn 4 hours later (6 hours after the nevirapine dose).
The blood will be analyzed for levels of nevirapine and possibly other HIV medicines. Some of the blood will be stored for later analysis of genes (cytochrome P450 and MDR1) that are involved in eliminating medicines from the body.
...
Detailed description
The overwhelming majority of HIV-infected persons reside in the developing world. As such, recent efforts have focused on providing antiretroviral pharmacotherapy to this population. However, there are a number of factors indigenous to non-Western HIV-infected patients that may alter their virologic, immunologic, and/or toxicologic response to antiretroviral therapy. Absorption, distribution, and clearance of antiretroviral medications may differ among patients residing in non-Western countries secondary to dietary influences, parasitic infection, and malabsorption. Genetic polymorphisms of drug metabolizing enzymes (cytochrome P450; CYP) and drug transporters (i.e. P-glycoprotein) may also contribute to altered pharmacokinetics among these patients. The purpose of this pilot, hypothesis-generating study is (1) to characterize the pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor nevirapine in a non-Western HIV-infected population (Kampala, Uganda) and in a similar cohort of HIV-infected individuals in the United States and (2) to compare pharmacokinetic parameter values between the groups. Twenty-five subjects from each site will participate. Subjects from the Ugandan site may participate regardless of their CD4+ lymphocyte count and viral load; they will be studied prior to the U.S. cohort. The U.S. group will be selected to include subjects that are matched by gender to their Ugandan counterparts. Subjects will have one pre-dose and two post-dose blood samples collected for the determination of nevirapine plasma concentrations. Samples will be analyzed using LC/MS-MS. Population pharmacokinetics parameter values (Cmax, Cmin, AUC, CL/F, Vd) will be determined using NONMEM(Trademark) and compared between groups. Blood samples collected during the study will also be used to determine CYP and MDR1 genotypes of study subjects in an effort to explain any observed differences in pharmacokinetics parameter values between the study populations.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- AST/SGOT less than or equal to 5 times the upper limit of normal (ULN)
- Serum creatinine less than or equal to 2 times the ULN
- Hemoglobin greater than or equal to 9.0 g/dL
Key exclusion criteria (14 listed)
- Presence of life-threatening or unstable renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or respiratory disease, as determined by medical records, 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.
- Laboratory values outside acceptable limits
- AST/SGOT less than 5 times the upper limit of normal (ULN)
- Serum creatinine greater than 2 times the ULN
- Hemoglobin less than 9.0 g/dL
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood draw | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 7477167Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med. 1995 Dec 7;333(23):1528-33. doi: 10.1056/NEJM199512073332303.
- Background: PubMed 9607828Harris M, Durakovic C, Rae S, Raboud J, Fransen S, Shillington A, Conway B, Montaner JS. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis. 1998 Jun;177(6):1514-20. doi: 10.1086/515317.
- Background: PubMed 9708400Hoetelmans RM, Reijers MH, Weverling GJ, ten Kate RW, Wit FW, Mulder JW, Weigel HM, Frissen PH, Roos M, Jurriaans S, Schuitemaker H, de Wolf F, Beijnen JH, Lange JM. The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy. AIDS. 1998 Jul 30;12(11):F111-5. doi: 10.1097/00002030-199811000-00002.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Blood draw in people with HIV Infection, run by National Institutes of Health Clinical Center (CC) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00054743, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017; AzTrials last refreshed its copy on 8 Nov 2026.