A Proof-of-concept Study of TR-012001, a Nasal Levodopa, in Patients with Parkinson’s Disease with OFF Episodes, Without Dopa Decarboxylase Inhibitor
Masahiro Nomoto1, Hayato Yabe2, Rina Ando3, Yasuhiro Sumiyoshi4, Takami Akagi4, Ryota Ise4, Yuki Akiyoshi5, Chizu Date4, Satoshi Nakano4, Ryosuke Suzuki4
1Saiseikai Imabari Hospital, 2Saiseikai Matsuyama Hospital, 3Ehime University Graduate School of Medicine, 4SNLD, Ltd., 5Tour de Medication Co., Ltd.
Objective:
TR-012001 is a novel investigational prefilled nasal levodopa product being developed as an on-demand therapy (ODT) to treat OFF episodes in 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.
Design/Methods:
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 day morning, without dopa decarboxylase inhibitor. Plasma levodopa concentration and efficacy were simultaneously assessed until 3 hours after a single nasal 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 a peak plasma levodopa concentration via nasal absorption within 15 minutes of dosing. Five patients in the TR-012001 group showed both motor improvement and increase in the number of taps, with 2 patients showing a 16-point reduction from baseline in MDS-UPDRSIII scores.
Conclusions:
The study has provided satisfactory safety and tolerability results for TR-012001 (total levodopa 40 mg). The rapid increase in the plasma levodopa concentration and the motor improvement seen in patients with PD supports further clinical development to provide a new ODT option for PD.
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