Clinical Trial Assessing Once Daily Raltegravir Administration (800 mg QD) in HIV-1-Infected Patients Receiving Unboosted Atazanavir (400 mg QD)- Based Antiretroviral Therapy

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Addition of raltegravir 800 mg QD to HAART

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias i Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Addition of raltegravir 800 mg QD to HAART	Drug: Addition of raltegravir 800 mg QD to HAART; Addition of raltegravir 800 mg QD to HAART; Other Names: HAART+RAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Raltegravir area under the curve (AUC) 24 hours and Cmin	Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	Baseline (BL), Day 10
Adherence	BL, Day 10

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Investigators: Principal Investigator: Clotet Bonaventura, MD,PhD, Lluita contra la Sida Foundation, HIV Unit

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ACTUAL): January 1, 2009
• Study Completion (ACTUAL): January 1, 2009

Study Registration Dates

• First Submitted: July 16, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (ESTIMATE): July 18, 2008

Study Record Updates

• Last Update Posted (ACTUAL): December 5, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: HIV; pharmacokinetics; Atazanavir; Raltegravir; once-daily
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: RALqd-ATV