HIV InfectionPhase 1NCT00001766
Drug Interactions Among Anti-HIV Agents
A Phase 1 study testing Amprenavir, Efavirenz, Abacavir, Nelfinavir, Ritonavir in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study examined the interactions of various drugs used to treat HIV infection in order to design larger studies of possible combinations for people who continue to have high viral levels despite combination therapy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infection
- What is being tested?
- Amprenavir, Efavirenz, Abacavir, Nelfinavir, Ritonavir
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1998to Aug 2003
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adults (greater than 18 years) infected with HIV-1.
- Plasma viral burden greater than 500 RNA copies/ml by bDNA method at screening visit while receiving a protease inhibitor as a part of combination therapy.
- Treatment with a protease inhibitor or inhibitor(s) for the preceding 20 weeks with no protease inhibitor drug change or dose interruption for greater than 3 days in the most recent 12 weeks.
- Laboratory values at screen:
- hemoglobin greater than 9 g/dl;
- granulocyte count greater than 900 cells/microL;
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- platelet count greater than 80,000 cells/microL;
- AST (SGOT) less than 151 U/L;
- Creatine less than 2 mg/dL.
- Willingness to avoid becoming pregnant or causing a pregnancy by use of effective methods which include surgical sterilization and barrier methods such as condoms and/or diaphragms. Hormonal methods of birth control are not acceptable unless barrier methods are also used because drug interactions may render their concentrations subtherapeutic.
- Willing and able to provide written informed consent.
- Negative serum or urine pregnancy test on the day of enrollment.
- No intolerance of ritonavir or nelfinavir.
Who cannot join
- Treatment with systemic corticosteroids at greater than physiologic replacement doses, interleukins, interferons, radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or an anticipated need for radiation or chemotherapy treatment within the next 48 weeks (with the exception of local treatment for Kaposi's sarcoma).
- Subjects suffering from serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction, which, in the opinion of the investigator, would compromise the safety of the patient.
- Current or anticipated therapy with other agents with documented activity against HIV-1 in vitro (other than stable maintenance dosing of foscarnet begun prior to screening).
- Prior exposure to abacavir, amprenavir or efavirenz.
- Concomitant therapy at entry with corticosteroids in other than replacement doses, chemotherapy, or investigational agents.
- Active, untreated opportunistic infection or other major illness that would, in the opinion of the investigator, increase the risk that adverse events might pose to the patient or might render the patient too ill to return for study visits.
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- Lymphoma not diagnosed within 5 years of study enrollment.
- Significant substance abuse or psychiatric illness that might interfere with assessment or compliance.
- Refusal to employ adequate means of birth control (non-hormonal methods); efavirenz is potentially teratofenic and conception must be avoided.
- Malabsorption or other gastrointestinal dysfunction which, in the opinion of the investigator, might interfere with drug absorption or render the patient unable to take oral medication.
- History of serious rash (erythema multiforme or Stevens-Johnson syndrome) caused by nevirapine or delavirdine.
- Treatment with phenobarbital, rifampin, rifabutin, midazolam, astemizole, cisapride, or triazolam unless subject is safely able to discontinue the drug(s) prior to receipt of study medications.
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: Pharmacokinetic Interactions Between Ritonavir, Amprenavir and Efavirenz and Nelfinavir, Amprenavir, and Efavirenz in People Infected With HIV
This study examined the interactions of various drugs used to treat HIV infection in order to design larger studies of possible combinations for people who continue to have high viral levels despite combination therapy.
HIV-infected patients 18 years of age and older who have a viral load of at least 500 copies/mL; who have received 20 weeks of protease inhibitor therapy, with the same protease inhibitors in combination therapy for the last 12 weeks; and who have never been treated with abacavir, amprenavir or efavirenz were enrolled.
Read more
All patients will receive 600 milligrams a day of efavirenz (a non-nucleoside reverse transcriptase inhibitor); 300 mg twice daily of abacavir (a nucleoside analog); and 1200 mg twice a day of amprenavir (a protease inhibitor). In addition to these drugs, six patients will receive 500 mg twice a day of ritonavir (a protease inhibitor); six patients will receive 200 mg twice a day of ritonavir; and 10 will receive 1250 mg twice a day of nelfinavir (a protease inhibitor).
Patients in the two ritonavir groups (500-mg and 200-mg dose groups) took abacavir and amprenavir for one week and then come to the clinic for blood tests to measure drug levels before taking their morning pills and at 1/2, 1, 2, 4, 8, and 12 hours after taking the medicines. They will then add ritonavir to their treatment regimen. After one week, they will return for blood tests as before. They will then add efavirenz to their regimen and had bloods drawn again after another 1 or 2 weeks.
Patients in the nelfinavir group took abacavir, amprenavir and nelfinavir for one week and then have blood sampling as described above for the ritonavir group. They will then add efavirenz to the regimen and repeat the blood tests again after another 1 or 2 weeks.
Participants are being seen in the clinic for follow-up only if they wish to continue to participate and if the regimen appears to offer clinical benefit.
Read the detailed description
In this study of pharmacokinetic interactions, (1) the effect of ritonavir on the pharmacokinetics of amprenavir; (2) the effect of efavirenz on the pharmacokinetics of amprenavir and ritonavir, and (3) the effect of efavirenz on the pharmacokinetics of amprenavir and nelfinavir were examined. Twenty-two patients who have a viral burden of at least 500 copies/mL on combination therapy with a protease inhibitor for at least 20 weeks were to be enrolled to receive open-label treatment, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 200 mg po BID and efavirenz 600 mg po QD, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 500 mg po BID and efavirenz 600 mg po QD, and 10 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, nelfinavir 1250 mg po BID and efavirenz 600 mg po QD. The groups enrolled sequentially: low-dose ritonavir combination group, then the full dose ritonavir combination group, and then the nelfinavir combination group. Subjects were seen at pre-entry, baseline (Day 1), and thereafter at study weeks 1 (serial sampling), 2 (serial sampling), 4, 8, 12, 16, 24 then every 8 weeks through one year. Patients discontinued current therapy and without a washout period began dosing. For the groups who will receive ritonavir, the schedule was: dose with abacavir and amprenavir and, after one-week, serial plasma sampling was performed for baseline amprenavir levels. Next ritonavir at the assigned dose was added (for the full-dose, there is a rapid dose escalation) and plasma sampling was repeated one week later; finally, efavirenz 600 mg once daily will be added and plasma sampling was again be repeated between 2 weeks after beginning the combination. For the nelfinavir group, the schedule was: dose with nelfinavir, amprenavir, and abacavir for one week and obtain serial plasma sampling, then add efavirenz for another week and obtain serial plasma sampling. Patients with a confirmed increase in viral burden of one log or greater from baseline will end study participation. The safety and antiviral activity of each combination were also assessed and continue to be assessed; toxicity management is outlined in the protocol. This study remains open in order to continue to provide these drugs to subjects who completed the original one-year study period and who wish to continue medications that appear, by viral load, to be of benefit to them.
- Conditions
- HIV Infection
- Being tested
- Amprenavir, Efavirenz, Abacavir, Nelfinavir, Ritonavir
- Keywords
- Abacavir, Salvage, Drug Interaction, Drug Levels, Anti-Viral, 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.
Amprenavir, Efavirenz, Abacavir, Nelfinavir, RitonavirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startAug 1998
- Study completionAug 2003
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.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Enrolment
- 22 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001766
- Sponsor's protocol ID
- 980147
- Other IDs
- 98-I-0147
- Status last verified
- Aug 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Livington DJ, Pazhanisamy S, Porter DJ, Partaledis JA, Tung RD, Painter GR. Weak binding of VX-478 to human plasma proteins and implications for anti-human immunodeficiency virus therapy. J Infect Dis. 1995 Nov;172(5):1238-45. doi: 10.1093/infdis/172.5.1238.
PubMed 7594659Faletto MB, Miller WH, Garvey EP, St Clair MH, Daluge SM, Good SS. Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1099-107. doi: 10.1128/AAC.41.5.1099.
PubMed 9145876Winslow DL, Garber S, Reid C, Scarnati H, Baker D, Rayner MM, Anton ED. Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266. AIDS. 1996 Sep;10(11):1205-9. doi: 10.1097/00002030-199609000-00005.
PubMed 8883581
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Interactions Between Ritonavir, Amprenavir and Efavirenz and Nelfinavir, Amprenavir, and Efavirenz in People Infected With HIV
- ClinicalTrials.gov ID
- NCT00001766
- Acronym / sponsor ID
- 980147
- Conditions
- HIV Infection
- Keywords
- Abacavir, Salvage, Drug Interaction, Drug Levels, Anti-Viral, HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 1998
- Study completion
- Aug 2003
- First posted
- 4 Nov 1999 (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 examined the interactions of various drugs used to treat HIV infection in order to design larger studies of possible combinations for people who continue to have high viral levels despite combination therapy.
HIV-infected patients 18 years of age and older who have a viral load of at least 500 copies/mL; who have received 20 weeks of protease inhibitor therapy, with the same protease inhibitors in combination therapy for the last 12 weeks; and who have never been treated with abacavir, amprenavir or efavirenz were enrolled.
All patients will receive 600 milligrams a day of efavirenz (a non-nucleoside reverse transcriptase inhibitor); 300 mg twice daily of abacavir (a nucleoside analog); and 1200 mg twice a day of amprenavir (a protease inhibitor). In addition to these drugs, six patients will receive 500 mg twice a day of ritonavir (a protease inhibitor); six patients will receive 200 mg twice a day of ritonavir; and 10 will receive 1250 mg twice a day of nelfinavir (a protease inhibitor).
Patients in the two ritonavir groups (500-mg and 200-mg dose groups) took abacavir and amprenavir for one week and then come to the clinic for blood tests to measure drug levels before taking their morning pills and at 1/2, 1, 2, 4, 8, and 12 hours after taking the medicines. They will then add ritonavir to their treatment regimen. After one week, they will return for blood tests as before. They will then add efavirenz to their regimen and had bloods drawn again after another 1 or 2 weeks.
Patients in the nelfinavir group took abacavir, amprenavir and nelfinavir for one week and then have blood sampling as described above for the ritonavir group. They will then add efavirenz to the regimen and repeat the blood tests again after another 1 or 2 weeks.
Participants are being seen in the clinic for follow-up only if they wish to continue to participate and if the regimen appears to offer clinical benefit.
Detailed description
In this study of pharmacokinetic interactions, (1) the effect of ritonavir on the pharmacokinetics of amprenavir; (2) the effect of efavirenz on the pharmacokinetics of amprenavir and ritonavir, and (3) the effect of efavirenz on the pharmacokinetics of amprenavir and nelfinavir were examined. Twenty-two patients who have a viral burden of at least 500 copies/mL on combination therapy with a protease inhibitor for at least 20 weeks were to be enrolled to receive open-label treatment, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 200 mg po BID and efavirenz 600 mg po QD, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 500 mg po BID and efavirenz 600 mg po QD, and 10 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, nelfinavir 1250 mg po BID and efavirenz 600 mg po QD. The groups enrolled sequentially: low-dose ritonavir combination group, then the full dose ritonavir combination group, and then the nelfinavir combination group. Subjects were seen at pre-entry, baseline (Day 1), and thereafter at study weeks 1 (serial sampling), 2 (serial sampling), 4, 8, 12, 16, 24 then every 8 weeks through one year. Patients discontinued current therapy and without a washout period began dosing. For the groups who will receive ritonavir, the schedule was: dose with abacavir and amprenavir and, after one-week, serial plasma sampling was performed for baseline amprenavir levels. Next ritonavir at the assigned dose was added (for the full-dose, there is a rapid dose escalation) and plasma sampling was repeated one week later; finally, efavirenz 600 mg once daily will be added and plasma sampling was again be repeated between 2 weeks after beginning the combination. For the nelfinavir group, the schedule was: dose with nelfinavir, amprenavir, and abacavir for one week and obtain serial plasma sampling, then add efavirenz for another week and obtain serial plasma sampling. Patients with a confirmed increase in viral burden of one log or greater from baseline will end study participation. The safety and antiviral activity of each combination were also assessed and continue to be assessed; toxicity management is outlined in the protocol. This study remains open in order to continue to provide these drugs to subjects who completed the original one-year study period and who wish to continue medications that appear, by viral load, to be of benefit to them.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Adults (greater than 18 years) infected with HIV-1.
- Plasma viral burden greater than 500 RNA copies/ml by bDNA method at screening visit while receiving a protease inhibitor as a part of combination therapy.
- Treatment with a protease inhibitor or inhibitor(s) for the preceding 20 weeks with no protease inhibitor drug change or dose interruption for greater than 3 days in the most recent 12 weeks.
- hemoglobin greater than 9 g/dl;
- granulocyte count greater than 900 cells/microL;
Key exclusion criteria (13 listed)
- Treatment with systemic corticosteroids at greater than physiologic replacement doses, interleukins, interferons, radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or an anticipated need for radiation or chemotherapy treatment within the next 48 weeks (with the exception of local treatment for Kaposi's sarcoma).
- Subjects suffering from serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction, which, in the opinion of the investigator, would compromise the safety of the patient.
- Current or anticipated therapy with other agents with documented activity against HIV-1 in vitro (other than stable maintenance dosing of foscarnet begun prior to screening).
- Prior exposure to abacavir, amprenavir or efavirenz.
- Concomitant therapy at entry with corticosteroids in other than replacement doses, chemotherapy, or investigational agents.
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 |
|---|---|---|
| Amprenavir, Efavirenz, Abacavir, Nelfinavir, Ritonavir | Drug | – |
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 4 Mar 2008.
- Background: PubMed 7594659Livington DJ, Pazhanisamy S, Porter DJ, Partaledis JA, Tung RD, Painter GR. Weak binding of VX-478 to human plasma proteins and implications for anti-human immunodeficiency virus therapy. J Infect Dis. 1995 Nov;172(5):1238-45. doi: 10.1093/infdis/172.5.1238.
- Background: PubMed 9145876Faletto MB, Miller WH, Garvey EP, St Clair MH, Daluge SM, Good SS. Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1099-107. doi: 10.1128/AAC.41.5.1099.
- Background: PubMed 8883581Winslow DL, Garber S, Reid C, Scarnati H, Baker D, Rayner MM, Anton ED. Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266. AIDS. 1996 Sep;10(11):1205-9. doi: 10.1097/00002030-199609000-00005.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Amprenavir, Efavirenz, Abacavir, Nelfinavir, Ritonavir in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 13 inclusion and 13 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 NCT00001766, 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 4 Mar 2008.