HIV InfectionsPhase 1/2NCT00622206
Pharmacokinetics of Low Dose Ritonavir
A Phase 1/2 study testing ritonavir and saquinavir in people with HIV Infections, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
Trial summary
Compare the Pharmacokinetics of ritonavir and saquinavir(using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg) Evaluate short term tolerability, safety and toxicity Evaluate if there is any relation between RTV concentration levels and boosting effect Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- ritonavir and saquinavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteThailand
- Study dates
- Jan 2008to Aug 2008
- Phase
- Phase 1/2
- 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
- Age > 18 years
- Documented positive test for HIV-1 infection
- HIV RNA viral load 50 < copies for at least 3 months
- Written informed consent
- On a Saquinavir 1500 mg based HAART regimen for at least 3 months
Who cannot join
- Pregnant or lactating
- Use of concomitant medication that may interfere with the pharmacokinetics of saquinavir/ritonavir
- Inability to understand the nature and extent of the study and the procedures required
- ALT/ AST more than 5x upper limit
- Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics of Low Dose Ritonavir in Thai Patients on a Saquinavir 1500 mg Based HAART Regimen
Compare the Pharmacokinetics of ritonavir and saquinavir(using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg) Evaluate short term tolerability, safety and toxicity Evaluate if there is any relation between RTV concentration levels and boosting effect
Read the detailed description
This study will focus on the combination of Saquinavir (SQV) and RTV. Firstly, this is because SQV is widely used in Thailand and has shown to be an adequate first and second line antiretroviral agent. Secondly, reduced dose of SQV (1600 mg OD) has proven to generate adequate efficacy and good pharmacokinetic parameters in the Thai population[5, 6]. Now 500 mg tablets of SQV are becoming more and more available, therefore a 1500 mg OD dose will be of more interest for our study. A TDM comparison study between SQV 1600 OD mg and SQV1500 mg OD has been done (Ananworanich et al, unpublished data) and did not show any difference in terms of drug concentrations . The efficacy of this regimen has shown to be adequate as described in the STACCATO cohort[7]. So we consider it safe to use the SQV 1500 mg OD in our study.
It is not clear what RTV concentrations are necessary to obtain good levels for SQV. In the study of Autar et al [5] no relation between RTV levels and boosting effect was described. Besides that it might well be that even the boosting levels of RTV contribute to the toxicity of the antiretroviral treatment.For instance, a study performed in healthy volunteers on RTV 100 mg BID monotherapy, showed a significant increase in total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides and a marked reduction of high-density lipoprotein (HDL)[8]. This last finding was confirmed in the study of Boyd et al (submitted) in Thai HIV-infected patients.
Preliminary data from HIVNAT 019 [9] suggests that lower boosting dosage still give adequate levels of the other PIs. In this open label 4 arm study one arm contains Lopinavir/Ritonavir 266/66 mg bid together with SQV 600 mg bid. Despite the dose reduction in all PIs, adequate PK levels were obtained. Two arms (23 patients) in this study used normal dose of RTV (100 mg bid) in combination with Lopinavir and Saquinavir. Five of them had maximal concentrations (Cmax) above the therapeutic level RTV (>2.1 mg/l). This finding is supported by clinical experience.
Therefore, looking into lower doses of RTV in the Thai population is of great interest A liquid formulation for RTV 50 mg will be used, as a capsule is not available yet. The liquid formulation has the same bioequivalence as the capsule and was used extensively during the time of manufactory problems of the Norvir capsule. Because of the bad taste of this formulation PK samples will be collected after one week, thereafter patients can return to their old regimen. A dose reduction of RTV can be of great importance for the Thai population as it prevents unnecessary toxicity and costs. If this PK study turns out to be adequate, an efficacy study can be performed and the boosting of other commonly used PI's, like IDV and Lopinavir, can be studied.
- Conditions
- HIV Infections
- Being tested
- ritonavir and saquinavir
- Keywords
- Pharmacokinetics, ritonavir, saquinavir, safety and toxicity, treatment experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ritonavir and saquinavirDrug
saquinavir/ritonavir 1500/100 mg or 1500/50 mg Twenty HIV-infected volunteers on stable doses of SQV/RTV 1500/100 mg OD for at least 3 months with an NRTI backbone and undetectable viral load will participate. After collecting samples for a full PK curve subjects will be switched to SQV/RTV 1500 /50 mg OD + 2NRTIs for 1 week before repeating the PK assessment. Blood samples will be drawn at T 0, 1, 2, 4, 6, 8, 10, 12 and 24 hours post ingestion. Consecutively to the assessment, subjects will return to SQV/RTV 1500/100 mg OD dosage.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Twenty HIV-infected volunteers on stable doses of SQV/RTV 1500/100 mg OD for at least 3 months with an NRTI backbone and undetectable viral load will participate. After collecting samples for a full PK curve subjects will be switched to SQV/RTV 1500 /50 mg OD + 2NRTIs for 1 week before repeating the PK assessment. Blood samples will be drawn at T 0, 1, 2, 4, 6, 8, 10, 12 and 24 hours post ingestion. Consecutively to the assessment, subjects will return to SQV/RTV 1500/100 mg OD dosage. Receives: Drug: ritonavir and saquinavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the Pharmacokinetics od ritonavir and saquinavir in Thai HIV-1 infected subjects using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg
Measured: 6 months and 1 week
Secondary outcomes (1)
Evaluate short term tolerability, safety and toxicity of this treatment strategy Evaluate if there is any relation between RTV concentration levels and boosting effect
Measured: 6 months and 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startJan 2008
- Primary completionApr 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- The HIV Netherlands Australia Thailand Research Collaboration
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kiat Ruxrungtham, MD, Principal investigator, The HIV Netherlands Australia Thailand Research Collaboration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00622206
- Sponsor's protocol ID
- HIV-NAT 083
- Other IDs
- IRB#188/50
- Status last verified
- Apr 2012
- First submitted
- 12 Feb 2008
- Last updated
- 5 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Avihingsanon A, van der Lugt J, Kerr SJ, Gorowara M, Chanmano S, Ohata P, Lange J, Cooper DA, Phanuphak P, Burger DM, Ruxrungtham K. A low dose of ritonavir-boosted atazanavir provides adequate pharmacokinetic parameters in HIV-1-infected Thai adults. Clin Pharmacol Ther. 2009 Apr;85(4):402-8. doi: 10.1038/clpt.2008.244. Epub 2008 Dec 31.
PubMed 19118378
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Low Dose Ritonavir in Thai Patients on a Saquinavir 1500 mg Based HAART Regimen
- ClinicalTrials.gov ID
- NCT00622206
- Acronym / sponsor ID
- HIV-NAT 083
- Conditions
- HIV Infections
- Keywords
- Pharmacokinetics, ritonavir, saquinavir, safety and toxicity, treatment experienced
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The HIV Netherlands Australia Thailand Research CollaborationUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Apr 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 22 Feb 2008 (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.
Compare the Pharmacokinetics of ritonavir and saquinavir(using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg) Evaluate short term tolerability, safety and toxicity Evaluate if there is any relation between RTV concentration levels and boosting effect
Detailed description
This study will focus on the combination of Saquinavir (SQV) and RTV. Firstly, this is because SQV is widely used in Thailand and has shown to be an adequate first and second line antiretroviral agent. Secondly, reduced dose of SQV (1600 mg OD) has proven to generate adequate efficacy and good pharmacokinetic parameters in the Thai population[5, 6]. Now 500 mg tablets of SQV are becoming more and more available, therefore a 1500 mg OD dose will be of more interest for our study. A TDM comparison study between SQV 1600 OD mg and SQV1500 mg OD has been done (Ananworanich et al, unpublished data) and did not show any difference in terms of drug concentrations . The efficacy of this regimen has shown to be adequate as described in the STACCATO cohort[7]. So we consider it safe to use the SQV 1500 mg OD in our study.
It is not clear what RTV concentrations are necessary to obtain good levels for SQV. In the study of Autar et al [5] no relation between RTV levels and boosting effect was described. Besides that it might well be that even the boosting levels of RTV contribute to the toxicity of the antiretroviral treatment.For instance, a study performed in healthy volunteers on RTV 100 mg BID monotherapy, showed a significant increase in total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides and a marked reduction of high-density lipoprotein (HDL)[8]. This last finding was confirmed in the study of Boyd et al (submitted) in Thai HIV-infected patients.
Preliminary data from HIVNAT 019 [9] suggests that lower boosting dosage still give adequate levels of the other PIs. In this open label 4 arm study one arm contains Lopinavir/Ritonavir 266/66 mg bid together with SQV 600 mg bid. Despite the dose reduction in all PIs, adequate PK levels were obtained. Two arms (23 patients) in this study used normal dose of RTV (100 mg bid) in combination with Lopinavir and Saquinavir. Five of them had maximal concentrations (Cmax) above the therapeutic level RTV (>2.1 mg/l). This finding is supported by clinical experience.
Therefore, looking into lower doses of RTV in the Thai population is of great interest A liquid formulation for RTV 50 mg will be used, as a capsule is not available yet. The liquid formulation has the same bioequivalence as the capsule and was used extensively during the time of manufactory problems of the Norvir capsule. Because of the bad taste of this formulation PK samples will be collected after one week, thereafter patients can return to their old regimen. A dose reduction of RTV can be of great importance for the Thai population as it prevents unnecessary toxicity and costs. If this PK study turns out to be adequate, an efficacy study can be performed and the boosting of other commonly used PI's, like IDV and Lopinavir, can be studied.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: ritonavir and saquinavirTwenty HIV-infected volunteers on stable doses of SQV/RTV 1500/100 mg OD for at least 3 months with an NRTI backbone and undetectable viral load will participate. After collecting samples for a full PK curve subjects will be switched to SQV/RTV 1500 /50 mg OD + 2NRTIs for 1 week before repeating the PK assessment. Blood samples will be drawn at T 0, 1, 2, 4, 6, 8, 10, 12 and 24 hours post ingestion. Consecutively to the assessment, subjects will return to SQV/RTV 1500/100 mg OD dosage. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Documented positive test for HIV-1 infection
- HIV RNA viral load 50 < copies for at least 3 months
- Written informed consent
- On a Saquinavir 1500 mg based HAART regimen for at least 3 months
Key exclusion criteria (5 listed)
- Pregnant or lactating
- Use of concomitant medication that may interfere with the pharmacokinetics of saquinavir/ritonavir
- Inability to understand the nature and extent of the study and the procedures required
- ALT/ AST more than 5x upper limit
- Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
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 |
|---|---|---|
| ritonavir and saquinavirsaquinavir/ritonavir 1500/100 mg or 1500/50 mg Twenty HIV-infected volunteers on stable doses of SQV/RTV 1500/100 mg OD for at least 3 months with an NRTI backbone and undetectable viral load will participate. After collecting samples for a full PK curve subjects will be switched to SQV/RTV 1500 /50 mg OD + 2NRTIs for 1 week before repeating the PK assessment. Blood samples will be drawn at T 0, 1, 2, 4, 6, 8, 10, 12 and 24 hours post ingestion. Consecutively to the assessment, subjects will return to SQV/RTV 1500/100 mg OD dosage. | Drug | 1 |
Primary outcome
To compare the Pharmacokinetics od ritonavir and saquinavir in Thai HIV-1 infected subjects using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg
Time frame: 6 months and 1 week
1 secondary outcome
Evaluate short term tolerability, safety and toxicity of this treatment strategy Evaluate if there is any relation between RTV concentration levels and boosting effect
Time frame: 6 months and 1 week
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 5 Apr 2012.
- Results publication: PubMed 19118378Avihingsanon A, van der Lugt J, Kerr SJ, Gorowara M, Chanmano S, Ohata P, Lange J, Cooper DA, Phanuphak P, Burger DM, Ruxrungtham K. A low dose of ritonavir-boosted atazanavir provides adequate pharmacokinetic parameters in HIV-1-infected Thai adults. Clin Pharmacol Ther. 2009 Apr;85(4):402-8. doi: 10.1038/clpt.2008.244. Epub 2008 Dec 31.
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)Link provided by the sponsor.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Kiat Ruxrungtham, MD principal investigator
The HIV Netherlands Australia Thailand Research Collaboration
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ritonavir and saquinavir in people with HIV Infections, run by The HIV Netherlands Australia Thailand Research Collaboration at 1 site in Thailand.
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 5 inclusion and 5 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 5 Apr 2012. 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 Thailand. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
What does the primary outcome measure?
To compare the Pharmacokinetics od ritonavir and saquinavir in Thai HIV-1 infected subjects using either Saquinavir /Ritonavir 1500/100 mg or 1500/50 mg (time frame: 6 months and 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00622206, which also lists 1 linked publication.
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 5 Apr 2012.