The Effect of Intermittent Rifampicin on Raltegravir (RIFRAL)
This study seeks to address the question of whether intermittent dosing of rifampicin influences the pharmacokinetics of raltegravir when co-administered. This study aims to look at what happens when rifampicin is taken 3 times a week with the standard dose and an increased dose of raltegravir. This is to find out the best dose of raltegravir to take when taking rifampicin 3 times a week. The study will be conducted in 18 healthy volunteers.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm, 3 Phase Study to Determine the Effect of Intermittent Dosing of Rifampicin on the Pharmacokinetics of Raltegravir in Healthy Volunteers|
- Change in raltegravir area under the curve (AUC) 0-12h [ Time Frame: Day 28 and day 33 ] [ Designated as safety issue: No ]
- Number of participants with adverse events [ Time Frame: 40 days (up to + 7 days) ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
The aim of this study is to optimise the dosing of raltegravir when coadministered intermittently with rifampicin. The co-administration of rifampicin and antiretrovirals (ARVs) is both complicated and problematic due to the potent induction of metabolism by rifampicin. Rifampicin induces cytochrome P450 (CYP) enzymes, which results in reduced plasma concentrations of two groups of ARVs, the protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). This pharmacokinetic interaction precludes the use of PIs and severely compromises the effectiveness of the NNRTI, nevirapine, as it potentially results in the loss of antiviral activity due to sub-therapeutic concentrations which will also lead to antiretroviral resistance.
Rifampicin also induces phase II enzymes including UDP-glucuronosyl transferase. The HIV integrase inhibitor, raltegravir, is primarily metabolised by UGT1A1 and therefore, there is the potential for a pharmacokinetic drug interaction with rifampicin. In fact, previous studies have shown a decrease in raltegravir AUC, CMAX, and C12 when co-administered with daily rifampicin. During directly observed therapy (DOTs) for TB, rifampicin is often given intermittently (e.g. 3 times a week). Although several studies have examined the interaction between raltegravir and daily rifampicin, currently there are no data regarding the pharmacokinetics of raltegravir when rifampicin is co-administered intermittently.
|Royal Liverpool & Broadgreen Univeristy Hospitals NHS Trust|
|Liverpool, United Kingdom, L7 8XP|
|Principal Investigator:||Saye Khoo||University of Liverpool|