more on mrk MK-7009
E. Lawitz and colleagues presented results from a study of the safety, tolerability, and antiviral activity of Merck's NS3/4A protease inhibitor MK-7009. The agent previously demonstrated potent activity in HCV replicon systems and infected chimpanzees.
In the present study, 33 treatment-naive and treatment-experienced chronic hepatitis C patients (85% men) with HCV genotype 1 (73% 1a) and high baseline viral load were randomly assigned to receive placebo or MK-7009 monotherapy at doses of 125 mg once-daily (qd), 600 mg qd, 25 mg twice-daily (bid), 75 mg bid, 250 mg bid, or 500 mg bid for 8 days. They were then followed for 14 days after the last dose.
After 8 days of therapy, the maximum observed decrease in HCV RNA was about 4 log10 IU/mL, and 70% overall achieved more than a 3 log10 decrease in HCV RNA at least once. The most common AEs overall were diarrhea and nausea. No serious adverse events (AEs) were reported, no pattern of laboratory or ECG abnormalities was observed, and no participants discontinued the study due to clinical or laboratory AEs.
"MK-7009 has potent antiviral activity during 8 days of monotherapy in patients with chronic genotype 1 HCV infection," the investigators concluded. "In these patients, MK-7009 was generally well-tolerated with no serious AEs, discontinuations due to AEs or safety laboratory abnormalities. Further development of this HCV NS3/4A protease inhibitor, including studies in combination with other anti-HCV agents, is warranted."
In a related pharmacokinetics study of MK-7009 in healthy HCV negative volunteers, investigators likewise observed no serious AEs. Taking the drug with a high-fat meal did not have a meaningful effect on plasma levels. Accumulation occurred over the 14-day dosing period in all subjects, and the apparent terminal half-life was about 4.5 hours regardless of dose, which suggests the feasibility of twice-daily dosing.
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