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Clinical Trial of Once-Daily Raltegravir Now Underway

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Merck announced this week that treatment-naive participants are now being enrolled in the Phase 3 ONCEMRK trial, which is evaluating the efficacy and safety of a ne formulation of the HIV integrase inhibitor raltegravir (Isentress) taken once rather than twice daily.

The current product label calls for raltegravir to be taken twice-daily, as prior studies found once-daily dosing to be less effective at initially suppressing viral load. However, once-daily dosing has been shown to be effective for maintenance therapy for people who have already achieved undetectable viral load. Many people prefer the convenience of once-daily treatment, and ONCEMRK is testing an investigational reformulated raltegravir designed to maintain adequate concentrations in the body over a longer period.

Below is an edited excerpt from a Merck press release describing the trial.

First Patient Enrolled in New Phase 3 Trial Program Investigating a Once-Daily Dosing Regimen of Isentress (raltegravir)

ONCEMRK Study Globally Enrolling Treatment-Naïve Adults with HIV-1

Whitehouse Station, N.J. -- June 5, 2014 -- Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the first patient has been enrolled in the company’s global Phase 3 clinical trial, ONCEMRK. ONCEMRK is assessing a once-daily investigational formulation of ISENTRESS (raltegravir), known as reformulated raltegravir, as part of combination HIV therapy for treatment-naive HIV-1-infected adults. ISENTRESS film-coated tablets are currently administered twice daily in accordance with the approved Prescribing Information.

"ISENTRESS has been a significant component of first-line HIV-1 treatment for more than six years, as a twice-daily component of antiretroviral therapy," said Jürgen Rockstroh, MD, University of Bonn, Bonn-Venusberg, Germany, a clinical investigator on this study. "We look forward to advancing our understanding of this new formulation of once-daily raltegravir with this new trial."

ISENTRESS is an integrase inhibitor indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in patients four weeks of age and older. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response. Severe, potentially life-threatening and fatal skin reactions have been reported with ISENTRESS. Additionally, during the initial phase of combination ARV treatment, immune reconstitution syndrome may occur.

The ONCEMRK trial is a multicenter, double-blind, randomized, active-controlled study evaluating the safety, efficacy, tolerability and pharmacokinetics of reformulated raltegravir 1200 mg (dosed as two 600 mg tablets) once daily, compared with ISENTRESS 400 mg twice daily, both in combination with once-daily tenofovir/emtricitabine over 96 weeks. The primary endpoint of the non-inferiority study is the proportion of patients achieving viral suppression (<40 copies/mL) at Week 48, which the company estimates will occur in the first half of 2016. Each patient in the study will receive treatment for approximately 96 weeks.

To learn more about the ONCEMRK trial, contact Merck at 1-888-577-8839 or visit www.merck.com/clinical-trials. Additional details can also be found online at www.clinicaltrials.gov/ct2/show/NCT02131233.

"We remain dedicated to investigating new applications for ISENTRESS and to further expanding our knowledge of this HIV-1 treatment," said Peter Sklar, MD, MPH, director, Clinical Research, Merck Research Laboratories. "Merck is proud to mark this notable milestone in the development of once-daily raltegravir and we look forward to continued patient enrollment worldwide over the coming months."

More than 160 centers in more than 25 countries are expected to participate in the ONCEMRK trial in the coming months. Merck is planning for the program to include approximately 750 patients worldwide.

Investigations of Raltegravir Once Daily

Reformulated raltegravir is a novel non-poloxamer based formulation. Based on the results of several Phase 1 studies, reformulated raltegravir has shown the potential to be investigated further for once daily use.

Data from the previous Phase 3 trial of raltegravir once daily, QDMRK, have contributed to the understanding of raltegravir pharmacokinetics and pharmacodynamics. QDMRK evaluated the long-term safety, tolerability and efficacy of a once-daily 800 mg ISENTRESS dose in a combination regimen compared with a twice-daily 400 mg ISENTRESS dose in combination. The once-daily arm of QDMRK studied the ISENTRESS poloxamer formulation given as two 400 mg tablets simultaneously. Results showed the primary endpoint of non-inferiority was not met, with 83 percent of treatment-naive adult HIV-1 infected patients achieving viral suppression (<50 copies/mL at Week 48) with the dosing regimen of 800 mg raltegravir once daily, compared with 89 percent of patients treated with ISENTRESS 400 mg twice daily. The safety and tolerability profiles of the two regimens were generally similar in the study and similar to the Prescribing Information for ISENTRESS.

About ISENTRESS

ISENTRESS is Merck's integrase inhibitor for the treatment of HIV-1 infection in adult and pediatric patients ages four weeks and older and weighing at least 3 kg as part of combination HIV therapy. ISENTRESS works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme and has demonstrated rapid antiviral activity. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. ISENTRESS is now approved as part of combination therapy in more than 76 countries for use in treatment-naive adult patients with HIV-1 and in more than 114 countries for use in treatment-experienced adult patients with HIV-1. ISENTRESS, in combination therapy, for use in children and adolescents with HIV-1 ages two years and older has also been approved for use in 35 countries, and ISENTRESS oral suspension for infants at least four weeks of age is approved for use in the U.S. Merck is continuing to move forward with filings of ISENTRESS for oral suspension in additional countries around the world.

To assist patients taking ISENTRESS, Merck offers the SUPPORT program, which provides personal support and patient advocacy regarding individual reimbursement issues. For more information about the SUPPORT program, please visit www.merckhelps.com or call 1-800-850-3430.

Please see Prescribing Information for ISENTRESS (raltegravir) at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf and Patient Information for ISENTRESS at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf.

6/11/14

Source

Merck. First Patient Enrolled in New Phase 3 Trial Program Investigating a Once-Daily Dosing Regimen of Isentress (raltegravir). Press release. June 5, 2014.