034: A Drug-Drug Interaction Study Between ABBV-903 & Midazolam in Healthy Participants

Statement of Purpose, Innovation or Hypothesis: ABBV-903 is an orally available inhibitor of main protease (Mpro) of SARS-CoV-2. This study was designed to evaluate the impact of ABBV-903 on the pharmacokinetics of midazolam, a sensitive probe substrate of cytochrome P450 (CYP)3A, and its metabolite, 1-OH-midazolam.

Description of Methods & Materials: This was a two-part, open label Phase 1 study in 24 healthy adult subjects. Part 1 of the study characterized the effect of multiple dosing of ABBV-903 for 10 days on the PK of midazolam and its metabolite, 1-OH-midazolam. Part 2 of the study evaluated the PK of midazolam and 1-OH-midazolam following 5 days of ABBV-903 dosing. Non-compartmental analysis was used to obtain estimates for the following pharmacokinetic parameters for midazolam and 1-OH-midazolam: C_max, T_max, t_1/2, AUC_t & AUC_inf. The exposures (C_max and AUC) of midazolam and 1-OH-midazolam were compared when administered alone in Period 1 and in combination with ABBV-903 in Period 2.

Data & Results: Midazolam was rapidly absorbed with a T_max ranging from ~0.5-2 hours in both periods of part 1 and 2 of the study. The harmonic mean of half-life ranged from ~3.8-5.4 -hours when dosed alone and ~7.1-7.6 hours when dosed in combination with ABBV-903. The AUC_inf and C_max of Midazolam were 4.3-4.6-fold and 2.4-2.6-fold higher, respectively when dosed in combination with ABBV-903 compared to dosed alone in both parts 1 and 2 of the study. The AUC_inf and C_max of 1-OH-midazolam were similar (~0.68-0.96-fold & ~1.07-1.19-fold, respectively) when midazolam was dosed in combination with ABBV-903 compared to dosed alone in both Part 1 and 2 of the study.

Interpretation, Conclusion or Significance: Administration of ABBV-903 for 5 or 10 days results in similar CYP3A4 inhibition.

Disclosures: E.A.C., A.O., S.L.Y., P.M.L., J.M.D., A.H.S., N.M.M. are Abbvie employees and may hold stock or options in the company. I.A. is a former employee of Abbvie and may hold Abbvie stocks or options.

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Additional Information/Authors: AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.