HIV InfectionsPhase 4NCT00995241
Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV
A Phase 4 study testing Raltegravir in people with HIV Infections, run by Germans Trias i Pujol Hospital at 2 sites in Spain.
Trial summary
The purpose of this study is to compare plasma and intracellular pharmacokinetic parameters of raltegravir 800 mg administered once daily in HIV infected patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesSpain
- Study dates
- Nov 2009to Dec 2009
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years.
- HIV documented infection.
- Stable antiretroviral treatment for at least 4 weeks.
- HIV viral load in plasma <50 copies / mL for at least 12 weeks
- Voluntary written informed consent.
Who cannot join
- AIDS-defining illness in the previous 4 weeks
- Suspicion of inadequate adherence to antiretroviral therapy
- In the case of women, pregnant or breastfeeding, or non-use of contraceptives
- History or suspicion of failure to cooperate adequately
- Concomitant therapy in the two weeks prior to inclusion in the study with atazanavir, tenofovir, NNRTI, rifampicin, inhibitors of proton pump or other drugs with known interactions with raltegravir.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
About this study
The purpose of this study is to compare plasma and intracellular pharmacokinetic parameters of raltegravir 800 mg administered once daily in HIV infected patients.
Read the detailed description
HIV integrase is the enzyme responsible for transferring the DNA encoded by HIV to host chromosomes, a necessary step for the replication of retroviruses. Raltegravir (RAL) is the first integrase inhibitor approved for HIV treatment of patients infected by this virus. RAL has demonstrated a marked antiretroviral activity against HIV strains resistant to other antiretroviral drug families and high virological efficacy in patients pre-treated so as naïve to antiretroviral treatment. In addition, its safety profile is very favourable.
Unlike what happens with other antiretrovirals such as protease inhibitors, there is not a relationship between the virological response to antiretroviral treatment with RAL and the trough concentration of drug in plasma. Similarly, in vitro studies have shown that, after infection of cultured cells, the rate of viral replication measured by p24 antigen production was continuing inhibited even when RAL was washed from the culture medium from the 8 hours after infection, suggesting the possibility of a post-antibiotic effect of the drug. Either way, as in the case of transcriptase inhibitor nucleoside analogues, this lack of correlation between pharmacokinetics and pharmacodynamics of RAL may only be the result of intracellular accumulation of drug in blood lymphocytes peripheral, which in turn could be explained either by setting the RAL to the pre-integration complex or through the saturation of certain cellular transporters responsible for pumping the RAL from the inside out-cell (efflux transporters). Anyway, the result would be a greater RAL intracellular half-life than plasmatic, which would translate into a clinically persistent antiretroviral effect compared with its concentration in plasma.
Based on the above is possible to suggest that the average life of RAL was longer in the peripheral blood lymphocytes than in plasma, and that this intracellular increased half-life could explain the absence of relationship between trough RAL concentration and its virological efficacy, post-antibiotic effect of RAL found in some studies in vitro which, on the other hand, could be relevant to the possible once-daily administration of raltegravir.
- Conditions
- HIV Infections
- Being tested
- Raltegravir
- Keywords
- Raltegravir, intracellular concentration, plasmatic concentration, HIV, 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.
RaltegravirDrug
Also called N/P
Raltegravir 800 mg / 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir 800 mg / 24 hours | Experimental | Raltegravir 800 mg / 24 hours Receives: Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasmatic and intracellular concentration of raltegravir
Measured: 10 days
Secondary outcomes (7)
Clearance, CL/F
Measured: 10 days
Volume of distribution, V/F
Measured: 10 days
Elimination half-life, t1/2
Measured: 10 days
Area under the plasma concentration-time curve during the dosing interval AUC0-24
Measured: 10 days
Maximum concentration
Measured: 10 days
Time to maximum concentration, Tmax
Measured: 10 days
Minimum concentration
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2009 (estimated)
- Study startNov 2009
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Responsible party
- Sponsor
- Investigators
- Jose Molto, MD,PhD, Principal investigator, Germans Trias i Pujol HospitalMarta Valle, MD,PhD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00995241
- Sponsor's protocol ID
- RAL-IC
- Status last verified
- Dec 2019
- First submitted
- 7 Oct 2009
- Last updated
- 5 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV
- ClinicalTrials.gov ID
- NCT00995241
- Acronym / sponsor ID
- RAL-IC
- Conditions
- HIV Infections
- Keywords
- Raltegravir, intracellular concentration, plasmatic concentration, HIV, Treatment experienced
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Study start
- Nov 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 15 Oct 2009 (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.
The purpose of this study is to compare plasma and intracellular pharmacokinetic parameters of raltegravir 800 mg administered once daily in HIV infected patients.
Detailed description
HIV integrase is the enzyme responsible for transferring the DNA encoded by HIV to host chromosomes, a necessary step for the replication of retroviruses. Raltegravir (RAL) is the first integrase inhibitor approved for HIV treatment of patients infected by this virus. RAL has demonstrated a marked antiretroviral activity against HIV strains resistant to other antiretroviral drug families and high virological efficacy in patients pre-treated so as naïve to antiretroviral treatment. In addition, its safety profile is very favourable.
Unlike what happens with other antiretrovirals such as protease inhibitors, there is not a relationship between the virological response to antiretroviral treatment with RAL and the trough concentration of drug in plasma. Similarly, in vitro studies have shown that, after infection of cultured cells, the rate of viral replication measured by p24 antigen production was continuing inhibited even when RAL was washed from the culture medium from the 8 hours after infection, suggesting the possibility of a post-antibiotic effect of the drug. Either way, as in the case of transcriptase inhibitor nucleoside analogues, this lack of correlation between pharmacokinetics and pharmacodynamics of RAL may only be the result of intracellular accumulation of drug in blood lymphocytes peripheral, which in turn could be explained either by setting the RAL to the pre-integration complex or through the saturation of certain cellular transporters responsible for pumping the RAL from the inside out-cell (efflux transporters). Anyway, the result would be a greater RAL intracellular half-life than plasmatic, which would translate into a clinically persistent antiretroviral effect compared with its concentration in plasma.
Based on the above is possible to suggest that the average life of RAL was longer in the peripheral blood lymphocytes than in plasma, and that this intracellular increased half-life could explain the absence of relationship between trough RAL concentration and its virological efficacy, post-antibiotic effect of RAL found in some studies in vitro which, on the other hand, could be relevant to the possible once-daily administration of raltegravir.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Raltegravir 800 mg / 24 hours | Experimental | Drug: RaltegravirRaltegravir 800 mg / 24 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years.
- HIV documented infection.
- Stable antiretroviral treatment for at least 4 weeks.
- HIV viral load in plasma <50 copies / mL for at least 12 weeks
- Voluntary written informed consent.
Key exclusion criteria (5 listed)
- AIDS-defining illness in the previous 4 weeks
- Suspicion of inadequate adherence to antiretroviral therapy
- In the case of women, pregnant or breastfeeding, or non-use of contraceptives
- History or suspicion of failure to cooperate adequately
- Concomitant therapy in the two weeks prior to inclusion in the study with atazanavir, tenofovir, NNRTI, rifampicin, inhibitors of proton pump or other drugs with known interactions with raltegravir.
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 |
|---|---|---|
| RaltegravirAlso: N/PRaltegravir 800 mg / 24 hours. | Drug | Raltegravir 800 mg / 24 hours |
Primary outcome
Plasmatic and intracellular concentration of raltegravir
Time frame: 10 days
7 secondary outcomes
Clearance, CL/F
Time frame: 10 days
Volume of distribution, V/F
Time frame: 10 days
Elimination half-life, t1/2
Time frame: 10 days
Area under the plasma concentration-time curve during the dosing interval AUC0-24
Time frame: 10 days
Maximum concentration
Time frame: 10 days
Time to maximum concentration, Tmax
Time frame: 10 days
Minimum concentration
Time frame: 10 days
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 Dec 2019.
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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.
Jose Molto, MD,PhD principal investigator
Germans Trias i Pujol Hospital
Marta Valle, MD,PhD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Raltegravir in people with HIV Infections, run by Germans Trias i Pujol Hospital at 2 sites in Spain.
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 Dec 2019. 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 Spain. 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.
What does the primary outcome measure?
Plasmatic and intracellular concentration of raltegravir (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Dec 2019.