Objective: To evaluate the safety, tolerability, levodopa pharmacokinetics, and exploratory efficacy of TR-012001 in Parkinson’s disease (PD).

Background: TR-012001 is a novel investigational prefilled nasal levodopa product being developed as an on-demand therapy (ODT) to treat OFF episodes in PD.

Method: In this proof-of-concept, phase II, randomized, single-blind, placebo-controlled, single‑dose, exploratory study, 12 patients with PD on treatment with levodopa‑containing agents, with OFF episodes, were randomized for treatment with TR‑012001 (total levodopa 40 mg; n=9) or placebo (n=3). Patients had an overnight washout of anti-PD drugs, including levodopa, and were treated with TR-012001 or placebo the following morning, without dopa decarboxylase inhibitor. Plasma levodopa concentration and efficacy were simultaneously assessed until 3 hours after a single, both nostrils dosing, and motor symptoms were evaluated using both MDS-UPDRSIII and the finger-tapping test for 30 seconds.

Results: The enrolled patients were in Hoehn–Yahr stages II-III (ON), with mean (standard deviation) baseline MDS-UPDRSIII (OFF) scores of 39.8 (14.2) for the TR-012001 group and 42.3 (2.3) for the placebo group. All 12 patients completed the study. All adverse drug reactions were mild and transient and categorized as nasal administration reactions. In the TR-012001 group, 8 of 9 patients achieved peak plasma levodopa concentration via nasal absorption within 15 minutes of dosing. Five patients in the TR-012001 group showed both motor improvement and an increase in the number of taps, with 2 patients showing a 16-point reduction from baseline in MDS-UPDRSIII scores.

Conclusion: The study reports satisfactory safety and tolerability results for TR-012001 (total levodopa 40 mg). The rapid increase in plasma levodopa concentration and the motor improvement seen in patients with PD support its further clinical development to provide a new ODT option for PD.

This work was previously presented at the 2025 Annual Meeting of the American Academy of Neurology (April 5–9, 2025) and the 66th Annual Meeting of the Japanese Society of Neurology (May 21–24, 2025).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-proof-of-concept-study-of-tr-012001-a-nasal-levodopa-in-patients-with-parkinsons-disease-with-off-episodes-without-dopa-decarboxylase-inhibitor/