A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects.

OBJECTIVE

To evaluate antiviral activity, tolerability, safety and pharmacokinetics of treatment with TMC125 (a non-nucleoside reverse transcriptase inhibitor), 900 mg twice daily for 7 days.

DESIGN

Randomized, double-blind, placebo-controlled, phase IIA clinical trial.

SETTING

Two hospital clinics in Moscow and St Petersburg, Russian Federation.

PARTICIPANTS

Nineteen antiretroviral-naive, HIV-1-infected subjects.

INTERVENTIONS

Randomization (2:1) was to twice daily treatment with either 900 mg TMC125 or matched placebo as monotherapy for 7 days.

MAIN OUTCOME MEASURES

Change in plasma HIV-1 RNA from baseline values (primary); change in CD4 cell counts from baseline, and evaluation of safety, tolerability and pharmacokinetics of TMC125 treatment (secondary).

RESULTS

A mean decrease from baseline in plasma HIV-1 RNA of 1.99 log10 copies/ml and 0.06 log10 copies/ml was achieved after 7 days in the TMC125 and placebo groups, respectively (P < 0.001). Plasma viral daily decay rates of 0.33 log10 copies/ml and 0.02 log10 copies/ml were observed in the TMC125 and placebo groups, respectively (P < 0.001). A steady-state plasma concentration of TMC125 was attained within 5 days of treatment with a mean minimum concentration of 246 ng/ml and a mean maximum concentration of 419 ng/ml. The majority of subjects did not report any adverse events. No abnormalities consistent with changes in blood chemistry, haematology, urinalysis, electrocardiograph or vital signs were observed.

CONCLUSIONS

TMC125 administered as monotherapy for 7 days yielded a 1.99 log10 copies/ml reduction in HIV-1 RNA in antiretroviral-naive, HIV-1-infected subjects. TMC125 was well tolerated and represents a promising and highly potent, next generation non-nucleoside reverse transcriptase inhibitor candidate.