Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV

This study has been completed.
Sponsor:
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00995241
First received: October 7, 2009
Last updated: September 9, 2010
Last verified: September 2010
  Purpose

The purpose of this study is to compare plasma and intracellular pharmacokinetic parameters of raltegravir 800 mg administered once daily in HIV infected patients.


Condition Intervention Phase
HIV Infections
Drug: Raltegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • Plasmatic and intracellular concentration of raltegravir [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clearance, CL/F [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Volume of distribution, V/F [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Elimination half-life, t1/2 [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve during the dosing interval AUC0-24 [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Maximum concentration [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Time to maximum concentration, Tmax [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Minimum concentration [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 5
Study Start Date: November 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir 800 mg / 24 hours
Raltegravir 800 mg / 24 hours
Drug: Raltegravir
Raltegravir 800 mg / 24 hours.
Other Name: N/P

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 years.
  2. HIV documented infection.
  3. Stable antiretroviral treatment for at least 4 weeks.
  4. HIV viral load in plasma <50 copies / mL for at least 12 weeks
  5. Voluntary written informed consent.

Exclusion Criteria:

  1. AIDS-defining illness in the previous 4 weeks
  2. Suspicion of inadequate adherence to antiretroviral therapy
  3. In the case of women, pregnant or breastfeeding, or non-use of contraceptives
  4. History or suspicion of failure to cooperate adequately
  5. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995241

Locations
Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Investigators
Principal Investigator: Jose Molto, MD,PhD Germans Trias i Pujol Hospital
Principal Investigator: Marta Valle, MD,PhD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  More Information

No publications provided

Responsible Party: Fundación LLuita contra la SIDA, Fundación Lluita contra la SIDA
ClinicalTrials.gov Identifier: NCT00995241     History of Changes
Other Study ID Numbers: RAL-IC
Study First Received: October 7, 2009
Last Updated: September 9, 2010
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Raltegravir
intracellular concentration
plasmatic concentration
HIV
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 19, 2014