Effect of food on pharmacokinetics of ACC017, a novel HIV‐1 integrase inhibitor, in healthy adult subjects

33 Background: ACC017, a novel HIV-1 integrase strand transfer inhibitor (INSTI) with potent anti-HIV activity, an in vitro resistance profile different from those of other INSTIs, and favourable preclinical safety and pharmacokinetic properties, which is being developed for the treatment of HIV-1 infection. The aim of this study was to investigate the effect of food on the single-dose pharmacokinetic properties of ACC017. Material and methods: A randomized, open-label, single-centre, two-period crossover study was conducted in 12 healthy Chinese adults. Twelve subjects, aged between 18 and 55 years old, were randomized in a 1:1 ratio to either fasting (group A) or fed (group B) conditions. During Period 1, after an overnight 10-h fast, the subjects in group A received a single 40 mg dose of ACC017 under fasting conditions, while the subjects in group B received ACC017 40 mg 30 min after a standard high-fat breakfast meal. Following a 7-day washout period, the subjects were crossed over to the opposite condition. Blood sampling, vital signs monitoring, electrocardiograms (ECGs), laboratory testing and pharmacokinetic analysis were performed at regular intervals to evaluate the effect of food on ACC017. This trial is registered with ClinicalTrials.gov, number NCT06278389. Results: All subjects (N = 12) completed the study, and none of them experienced any adverse events (AEs) or serious adverse events (SAEs) under either fasting or fed conditions. The average maximum plasma concentration (Cmax) of ACC017 was 261.6 ng/mL in the fasting state and 447.9 ng/mL in the fed state. Food intake increased the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC0-t) from 16678.0 h*ng/mL (fasting state) to 27597.9 h*ng/mL (fed state) and the average area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) from 17050.0 h*ng/mL to 28037.5 h*ng/mL. The geometric mean value of Cmax was increased by 83.90% in the fed state, as were AUC0-t by 70.22% and AUC0-∞ by 68.98%. The median time to Cmax (Tmax) was 4 h in both states. The mean terminal half-life was also similar (12.0 vs. 11.5 h). Conclusions: This study demonstrates that a standard high-fat breakfast modestly increases the exposure to a single oral dose of ACC017 40 mg, but it did not affect the absorption rate. The exposure increases of ACC017 (68.98% to 83.90%) are not anticipated to impact safety. Clinical experience from phase IIa trials further supports this recommendation.