Objective: To assess the safety, tolerability, and pharmacokinetics (PK) of NE3107 in carbidopa/levodopa (C/L)-treated patients with Parkinson’s disease (PD)

Background: Disease-modifying therapies that augment the efficacy of levodopa and alleviate levodopa-induced dyskinesia (LID) are urgently needed. Chronic inflammation drives PD and may contribute to LID. NE3107 is an oral, blood-brain barrier–permeable molecule that binds extracellular signal regulated kinase (ERK) in pathology-specific signaling pathways. It inhibits ERK activation and downstream inflammatory cascades, without affecting homeostasis. In PD animal models, NE3107 treatment was associated with improved motor function, reduced LID, and increased survival of dopaminergic neurons. We conducted a phase 2a, double-blind, placebo-controlled study to evaluate the safety, tolerability, efficacy, and PK of NE3107 in C/L-treated patients with PD.

Method: Forty patients aged 30 to 80 years old with a diagnosis of PD, a marked response to levodopa, and a history of motor fluctuations with early morning OFF episodes were enrolled. Patients were randomized 1:1 to receive 20 mg oral NE3107 twice daily or matching placebo for 28 days. All patients received their usual C/L regimen and adjunctive PD medications. PK assessments evaluated the potential change in levodopa PK profile on day 14 in the presence of steady-state NE3107, compared to baseline (day 1) before initiation of NE3107 dosing, and included C_max, T_max, and AUC. Treatment-emergent and serious adverse events evaluations continued to day 35.

Results: Twenty patients received NE3107 + C/L, and 19 patients received placebo + C/L. One patient voluntarily withdrew from the study. All patients tolerated NE3107 well, and no drug-related adverse events were reported. NE3107 did not affect the PK profile of levodopa; the mean levodopa AUC values on day 1 (4243.08 ng.h/mL) and day 14 (4127.41 ng.h/mL) were comparable.

Conclusion: Our data demonstrate that NE3107 was well-tolerated and did not significantly alter the PK profile of levodopa. These data will assist in the interpretation of any clinical effects seen in PD patients receiving NE3107 and support the safety of using NE3107 with levodopa in subsequent late-phase clinical investigations in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-and-pharmacokinetics-of-anti-inflammatory-ne3107-treatment-in-carbidopa-levodopa-treated-patients-with-parkinsons-disease-a-phase-2a-double-blind-placebo-controlled-study/