No Meaningful Drug-Drug Interactions Are Associated with the Coadministration of ACC007, Lamivudine, and Tenofovir Disoproxil Fumarate.

ABSTRACT

ACC007 is a new-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with favorable pharmacokinetic and safety profiles. NNRTIs are typically administered in combination with two nucleoside reverse transcriptase inhibitors as first-line recommended regimens in several guidelines. Therefore, this open-label, randomized, single-period, parallel-cohort study aimed to assess the drug-drug interactions (DDIs) and safety profiles of ACC007 in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) in healthy subjects. All 24 screened subjects were randomly assigned to group A or B. On days 1 to 17, 3TC at 300 mg and TDF at 300 mg were taken orally by group A, and ACC007 at 300 mg was coadministered on days 8 to 17. On days 1 to 17, 300 mg of ACC007 was taken orally by group B, and 300 mg 3TC and 300 mg TDF were coadministered on days 8 to 17. When we compared 3TC-TDF versus 3TC-TDF-ACC007 DDIs, the geometric mean ratios (GMRs, with 90% confidence intervals [CIs] in parentheses) of the maximum concentration at steady state (Cmax,ss) and area under the concentration-time curve from 0 h to infinity (i.e., at steady state; AUCss) values for TDF were 108.14% (95.68 to 122.22%) and 89.90% (82.67 to 97.76%) (P = 0.344); for 3TC, these values were 113.48% (91.45 to 140.82%) and 95.33% (83.61 to 108.7%) (P = 0.629). When ACC007 alone was compared to the combination 3TC-TDF-ACC007, the GMRs (90% CIs) of the Cmax,ss and AUCss values for ACC007 were 89.00% (76.35 to 103.74%) and 82.57% (73.27 to 93.05%) (P = 0.375). The coadministration of 3TC-TDF-ACC007 did not significantly affect the time to maximum concentration of any of the drugs in terms of P values. ACC007 combined with 3TC-TDF was generally well tolerated during daily dosing for 17 days with no serious adverse events. Overall, ACC007 and 3TC-TDF had no significant or meaningful interactions and a favorable safety profile, which supports the use of the combination regimen.