Merck (NYSE:MRK), known as MSD outside the United States and Canada, is presenting pharmacokinetic data this week on investigational formulations of a once daily (QD) dose of ISENTRESS at the 14th European AIDS Conference (EACS), sponsored by the European AIDS Clinical Society. The meeting is currently taking place in Brussels, Belgium, Oct. 16-19, 2013. The poster presentation A Single Dose Food Effect Study of Raltegravir Formulations (Poster #PE10/17) will be presented Thursday, Oct. 17, and Friday, Oct. 18, from 12:00 p.m. to 2:00 p.m. CET. Based on the results of this study and other data, Merck plans to initiate a Phase III clinical study on a once daily dosing regimen of ISENTRESS in early 2014, pending review by regulatory agencies. ISENTRESS is administered twice daily, in accordance with the approved Prescribing Information.
"We previously studied once daily ISENTRESS in a combination regimen and in that study, the once daily formulation did not meet the non-inferiority endpoint compared to twice daily ISENTRESS," said Jeff Chodakewitz, M.D., vice president, global clinical development, infectious disease & vaccines, Merck Research Laboratories. "The data we are presenting at the European AIDS Clinical Society conference, as well as other currently available data, provide a strong scientific basis to continue our investigational work toward a once daily dosing regimen."
The primary endpoint of the previous Phase III trial (QDMRK) was non-inferiority of the once daily 800 mg dose in a combination regimen compared to the twice daily 400 mg dose in combination. The endpoint was not met, as the once daily dose studied was inferior to the twice daily dose. Results showed that at 48 weeks, 83 percent of treatment-naïve adult HIV-1 infected patients achieved viral suppression with the dosing regimen of 800 mg ISENTRESS (raltegravir) once daily, compared with 89 percent of patients treated with ISENTRESS 400 mg twice daily. Thus, non-inferiority was not met in the QDMRK trial. The safety and tolerability profiles of the two regimens were generally similar in the study and similar to the Prescribing Information for ISENTRESS. The study was concluded in 2010, and the results were presented at the 2011 Conference on Retroviruses and Opportunistic Infections (CROI) as well as published in The Lancet.
The Single Dose Food Effect Study of Raltegravir Formulations presented at EACS was an open-label, randomized, two cohort, three period, three treatment, six sequence, crossover study in 36 healthy subjects. The study evaluated the single dose pharmacokinetics and food effect of two different formulations of raltegravir, both given in a single 1200 mg dose at fasted, low-fat fed, and high-fat fed states. The results indicated that both formulations have the potential to be investigated further for once daily use in a clinical study, but showed that the pharmacokinetics of the reformulated version of raltegravir were less affected by food.
ISENTRESS is an integrase inhibitor indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adults. This indication is based on analyses of plasma HIV-1 RNA levels in three double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, three-class ARV [non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor (PI)] treatment-experienced adult patients through 96 weeks and one was conducted in treatment-naïve adults through 240 weeks. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response.