Clinical trial NCT00718536: Clinical Trial Assessing Once Daily Raltegravir Administration (800 mg QD) in HIV-1-Infected Patients Receiving Unboosted Atazanavir (400 mg QD)- Based Antiretroviral Therapy
Official title: Clinical Trial Assessing Once Daily Raltegravir Administration (800 mg QD) in HIV-1-Infected Patients Receiving Unboosted Atazanavir (400 mg QD)- Based Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Atazanavir
Raltegravir
once-daily
pharmacokinetics
HIV
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2008-07-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The co-administration of raltegravir with medicinal products that are knouwn to be potent UGT1A1 inhibitors, such as atazanavir, may increase plasma levels of raltegravir. So once daily raltegravir (800 mg QD), instead of twice a day (400 mg BID), could be an appropriate therapeutic option in HIV-infected patients also receiving atazanavir-containing antiretroviral regimens. In this study, pharmacokinetic data supporting this hypothesis are recovered.

Detailed description: Treatment adherence is crucial for the effectiveness of antiretroviral therapy, and, in an attempt to promote treatment adherence by the patients, once daily (QD) regimens are preferred rather than twice daily (BID) regimens.

The dose of 400 mg BID of raltegravir has been recently licensed for the treatment of human immunodeficiency virus (HIV-1) infection in treatment-experienced adult patients.

Raltegravir is eliminated mainly by metabolism via uridine diphosphate glucuronyl transferase (UGT1A1)-mediated glucuronidation pathway. Thus, co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors, such as atazanavir, may increase plasma levels of raltegravir.

Based on these data, it could be hypothesized that once daily raltegravir (800 mg QD) could be an appropriate therapeutic option in HIV-infected patients also receiving atazanavir-containing antiretroviral regimens. However, pharmacokinetic data supporting this hypothesis are lacking.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 to 65 years old with documented HIV-1 infection.
2. Patients on antiretroviral regimen that includes atazanavir 400mg QD for at least 4 weeks.
3. Complete virological suppression (\<50 copies/mL) for at least 12 months.
4. Voluntary written informed consent.
5. Ability of compliance with visit schedule.

Exclusion Criteria:

1. AIDS defining condition within 4 weeks prior to the initiation of the study.
2. Concomitant treatment with ritonavir as well as with inducers (NNRTI, rifampin, carbamazepine, phenytoin, phenobarbital, valproic acid, etc) or inhibitors (probenecid, etc) of the uridine diphosphate glucuronyl transferase within 2 weeks before the screening visit.
3. Concomitant therapy with tenofovir.
4. History or suspected poor adherence to HAART.
5. History of drug allergy to raltegravir

Primary outcomes:
measure: Raltegravir area under the curve (AUC) 24 hours and Cmin
timeFrame: Day 10
Secondary outcomes:
measure: Adverse events
timeFrame: Baseline (BL), Day 10
measure: Adherence
timeFrame: BL, Day 10
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
affiliation: Lluita contra la Sida Foundation, HIV Unit
name: Clotet Bonaventura, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: