Cenicriviroc + Omeprazole = Precautionary

Effect on Concentration

Cenicriviroc
Decrease
Applies within class?
No
Omeprazole
Decrease
Applies within class?
No

Pharmacologic Effects

Cenicriviroc
Effect
N/A
Applies within class?
No
Omeprazole
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 23-Jul-2018

Summary

Sources

Cenicriviroc versus Omeprazole ^

Study Design

Phase 1, single- and multiple-dose, open-label study conducted in two parts. Part 1: Group 1, 12 subjects received OME 20 or 40 mg od for 6 days and CVC 150 mg 2 h after OME dose on Day 6; Group 2,12 subjects received FAM 40 mg 2 h before, or 2 or 12 h after CVC 150 mg. Part 2: Group 3, 24 subjects received CVC 150 mg od for 10 days to achieve steady-state concentrations; subjects were then randomised to CVC 150 mg od (Group 4; N = 12) or CVC 300 mg od (Group 5; N = 12) together with OME 20 mg od (3 h post-CVC dose) for 10 days. Plasma samples were collected over 24h post-CVC dose. CVC PK parameters were determined using non-compartmental methods. Least square geometric means, geometric mean ratios and confidence intervals (CIs) were calculated.

Study Results

For Part I: OME 20 and 40 mg, 2 h pre-CVC, decreased CVC exposures (AUC0–24: 66% and 77% reduction, respectively); FAM administration 2 h pre-CVC decreased CVC exposures (AUC0–24: 67% reduction), but it did not have a meaningful effect at 2 h or 12 h post- CVC (AUC0–24: 21% and 1% increase, respectively). For Part 2: the effect of OME 20 mg on CVC PK was reduced when administered 3 h post-CVC 150 mg at steady state (AUC0–tau: 40% reduction). Cmin values in all Group 4 subjects were above the target trough CVC concentration of 40 ng/mL. When OME 20 mg was administered 3 h post-CVC 300 mg at steady state, CVC AUC0–tau increased by 71% relative to CVC 150 mg alone. Co-administration was well tolerated. The majority of adverse events (AEs) were mild, with no serious AEs or AEs leading to discontinuation.

Study Conclusions

These findings suggest that acid-reducing agents should be administered at least 2–3 h after CVC dose to ensure that adequate CVC concentrations are maintained. When co-administered, OME should preferably be dosed at 20 mg 3 h following CVC 150 mg. FAM 40 mg should be given 2–12 h following CVC 150 mg.

References

Seyedkazemi S, Harris S, Willett M, Chang W, Clark JC, Smith P, Lefebvre E. Effect of acid-reducing agents omeprazole and famotidine on the pharmacokinetics of cenicriviroc in healthy adults . International Liver Congress. Amsterdam, Netherlands. 2017; April 2017.