To assess the bioequivalence (BE) and relative bioavailability (BA) between a once-daily (QD) extended release formulation of deutetrabenazine and the approved twice-daily (BID) formulation at steady state under fed conditions.
In a phase 1 study (TV50717-BE-10179) using a randomized cross-over design, healthy adult males and females (n=262) received 24 mg QD formulation (test) as a once daily administration and 12 mg BID formulation (reference) as a twice daily administration, each for 7 days in fed state. Safety was assessed throughout the study and pharmacokinetic (PK) blood sampling occurred on days 4-7. Test-to-reference geometric mean ratios (GMRs) and 90%CIs for BE acceptance limits (80.00% to 125.00%) were computed for PK parameters (area under the plasma concentration curve over 24-hours at steady-state [AUC0-24hr,ss] and maximum plasma concentration at steady-state [C max,ss]) of deutetrabenazine, active metabolites, deuterated α-HTBZ and β-HTBZ, and total (α+β)-HTBZ. Relative BA was assessed for Cmax,ss of the active metabolites (individually and as a total sum).
The GMRs (90%CIs) for AUC0-24hr,ss were 115.15% (110.38–120.14%) for deutetrabenazine, 95.40% (94.13–96.69%) for α-HTBZ, 94.13% (92.35–95.94%) for β-HTBZ, and 95.05% (93.67–96.46%) for total (α+β)-HTBZ. GMRs of Cmax,ss were 95.09% (90.60-99.80%) for deutetrabenazine, 79.56% (78.21-80.94%) for α-HTBZ, 74.85% (73.13-76.60%) for β-HTBZ and 77.71% (76.26-79.16%) for total (α+β)-HTBZ. No new safety findings emerged in this study.
At steady state, deutetrabenazine administered as the QD formulation was bioequivalent to the approved BID formulation for both AUC and Cmax. The active metabolites at steady state were bioequivalent with regard to AUC between the QD and BID formulation; Cmax was slightly lower for the QD formulation compared to the BID formulation.