SELZENTRY SUMMARY
SELZENTRY (maraviroc) is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Blocking this interaction prevents CCR5-tropic HIV-1 entry into cells.
SELZENTRY, in combination with other antiretroviral agents, is indicated for treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of SELZENTRY of 24 weeks duration. Both studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI, or enfuvirtide) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The following points should be considered when initiating therapy with SELZENTRY:
- Tropism testing and treatment history should guide the use of SELZENTRY.
- Use of SELZENTRY is not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a phase 2 study of this patient group.
- The safety and efficacy of SELZENTRY have not been established in treatment-naïve adult patients or pediatric patients.
There are no study results demonstrating the effect of SELZENTRY on clinical progression of HIV-1.
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NEWS HIGHLIGHTS
Published Studies Related to Selzentry (Maraviroc)
A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. [2009.06.01]
BACKGROUND: Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual- or mixed-tropic strains of human immunodeficiency virus type 1 (HIV-1). A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1... CONCLUSIONS: In this exploratory study involving extensively treatment-experienced patients with advanced, non-R5 HIV-1 infection, neither superiority nor noninferiority was statistically demonstrated for either maraviroc dosage compared with placebo at 24 weeks of treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00098748 .
Maraviroc for previously treated patients with R5 HIV-1 infection. [2008.10.02]
BACKGROUND: CC chemokine receptor 5 antagonists are a new class of antiretroviral agents... CONCLUSIONS: Maraviroc, as compared with placebo, resulted in significantly greater suppression of HIV-1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV-1 who were receiving OBT. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.) 2008 Massachusetts Medical Society
Maraviroc: integration of a new antiretroviral drug class into clinical practice. [2008.06]
Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the US) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire FDA and EMEA approval. It is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring only the R5 virus...
Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects. [2008.04]
AIMS: To assess the effect of a single dose of maraviroc on the QTc interval in healthy subjects and to evaluate the QTc interval-concentration relationship... CONCLUSIONS: Single doses of maraviroc, up to and including 900 mg, had no clinically relevant effect on QTcF or QTcI. At all maraviroc doses and for both end-points, the mean difference from placebo for QTc was < 4 ms. There was no apparent relationship between QT interval and maraviroc plasma concentration up to 2363 ng ml(-1). This conclusion held in both male and female subjects, and there was no evidence of a change in the QT/RR relationship with concentration.
Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. [2008.04]
AIMS: To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist... CONCLUSIONS: Potent CYP3A4 inhibitors, including ketoconazole and protease inhibitors (except TPV/r), increase maraviroc exposure. Downward adjustment of the maraviroc dose during co-administration with protease inhibitors can compensate for the interaction. TPV/r does not affect the steady-state pharmacokinetics of maraviroc, and hence no dose adjustment would be warranted.
Clinical Trials Related to Selzentry (Maraviroc)
Investigation Of Safety And Pharmacokinetics Following A Single Oral Dose Of 300 Mg Maraviroc In Healthy Male Japanese Volunteers [Not yet recruiting]
To confirm safety and pharmacokinetics of maraviroc following a single oral dose of 300 mg
maraviroc in healthy male Japanese volunteers.
Evaluation of Maraviroc Intensification in HIV Infected Patients With Insufficient Immune Restoration [Not yet recruiting]
This pilot study aims to evaluate Maraviroc intensification strategy during 24 weeks in HIV
infected patients under efficient (CV< 50 cp/mL), controlled antiretroviral therapy (≥ 6
months) and uncompleted immune restoration (CD4<350 cells/mL and CD4 earning <100 cells/mL
during last 24 months).
The study will include 60 patients whose follow up is carried out for 48 weeks. recruitment
period will be maintained for 12 months.
Study in Healthy Males to Measure Maraviroc in Blood, Saliva, Seminal Fluid, and Rectal Tissue [Recruiting]
This study is being conducted to look at how the body handles the drug maraviroc. It will
measure the amount of maraviroc in blood, semen, saliva and in the rectum of men. The aim
is to understand how much of the drug (taken by mouth) reaches the oral, reproductive and
intestinal tracts. It is believed that the presence of this drug in these areas may be
beneficial in preventing the AIDS virus (HIV) from being passed from one person to another.
The study will take samples of blood, saliva, semen and rectal mucosal tissue to measure
drug levels. This study will also collect information on side effects.
CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy [Not yet recruiting]
This research study is being done to find out how the immune system in the small intestines
improves after taking antiretroviral (anti-HIV) medications. Biopsies (small snips of
tissue) will be taken from the part of the intestines just below the stomach, and will be
studied in the laboratory. The main purpose of this study is to measure the increase in the
numbers of immune cells in the intestines to see if this number is related to the amount of
medication that reaches the intestinal tissue, and the amount of virus that is still hiding
there.
Subjects are either normal control subjects without HIV or, are HIV positive and are about
to start HIV medications. As part of this study, HIV positive patients will be randomized
to receive one of three possible combinations of medications.
1. maraviroc (Selzentry) in combination with 2 NRTIs (dual nucleoside reverse
transcriptase inhibitor) or
2. maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse
transcriptase inhibitor) or
3. efavirenz (Sustiva) in combination with 2 NRTIs (dual nucleoside reverse transcriptase
inhibitor)
Both Maraviroc and Raltegravir each represent new classes of medications in the way that
they interfere with HIV making copies of itself. Maraviroc attaches to the surface of the
T-cell that the virus uses to get into the cell and is therefore known as an entry
inhibitor. Raltegravir blocks the virus from inserting itself into the DNA of the infected
cell's nucleus and is therefore known as an Integrase Inhibitor. We hope to learn more
about how antiretroviral drugs affect T cells and how immune function restores itself when
HIV infection is treated.
An Open Label Pharmacokinetic, Safety And Efficacy Study Of Maraviroc In Combination With Background Therapy For The Treatment Of HIV-1 Infected, CCR5 -Tropic Children [Recruiting]
The primary purpose of this study is to determine the pharmacokinetic properties (what the
body does to maraviroc) and to determine a suitable dosing schedule of maraviroc in HIV-1
infected children and adolescents. This study will also determine whether maraviroc is safe
to use in children and adolescents.
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