9:04AM Supernus Pharma announces release of 'exciting' new clinical data on Trokendi XR; concentration-time profile of once-daily SPN-538 was associated with significantly less negative impact on COWA despite PK bioequivalence to b.i.d. TPM-IR on all standard PK parameters (SUPN) 6.88 : Rationale: Dose-management strategies improve the tolerability of TPM, a potent, broad-spectrum AED that can cause distinctive cognitive symptoms (e.g., word-finding difficulty). Neuropsychometric tests have shown significant negative changes, especially in verbal fluency, in a relatively small subset of patients receiving TPM-IR. SPN-538 (Trokendi XR, Supernus Pharmaceuticals, Inc.) is a novel extended-release, once-daily capsule formulation of TPM that may improve tolerability and adherence. In a crossover study in healthy volunteers establishing bioequivalence of once-daily SPN-538 to b.i.d. TPM-IR (200 mg/day), effects of treatments on cognitive function were compared.
Results: In the per-protocol analysis of all subjects with data, COWA change scores favored once-daily SPN-538 over b.i.d. TPM-IR at all test points; differences were significant at 50 (P=0.05) and 100 mg/day and for the entire treatment period. Subjects with moderate/severe negative COWA changes: TPM-IR, 42%; SPN-538, 12%. Similar patterns for DSST changes did not reach statistical significance.
Conclusion: Based on the per-protocol analysis of COWA change scores, the concentration-time profile of once-daily SPN-538 was associated with significantly less negative impact on COWA despite PK bioequivalence to b.i.d. TPM-IR on all standard PK parameters, similar Cavg0-24, and nearly identical mean TPM concentrations when cognitive function tests were performed 18 and 10 hrs after Tmax. Once-daily SPN-538 produces more consistent TPM plasma concentrations due to a markedly slower absorption rate.
