Abstract Details

Title A Proof-of-concept Study of TR-012001, a Nasal Levodopa, in Patients with Parkinson’s Disease with OFF Episodes, Without Dopa Decarboxylase Inhibitor

Topic Movement Disorders

Presentation(s) P11 - Poster Session 11 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-009

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.

Authors/Disclosures
Yasuhiro Sumiyoshi PRESENTER	Mr. Sumiyoshi has received personal compensation for serving as an employee of Shin Nippon Biomedical Laboratories, Ltd., Japan. Mr. Sumiyoshi has received personal compensation for serving as an employee of SNLD, Ltd., Japan.
Masahiro Nomoto, MD	Prof. Nomoto has nothing to disclose.
Hayato Yabe, MD, PhD	Dr. Yabe has nothing to disclose.
Rina Ando, MD	Dr. Ando has nothing to disclose.
Takami Akagi, PhD	Dr. Akagi has received personal compensation for serving as an employee of SNLD, Ltd., Japan. Dr. Akagi has received personal compensation for serving as an employee of Shin Nippon Biomedical Laboratories, Ltd., Japan.
Ryota Ise, PhD	Dr. Ise has received personal compensation for serving as an employee of SNLD, Ltd., Japan. Dr. Ise has received personal compensation for serving as an employee of Shin Nippon Biomedical Laboratories, Ltd., Japan.
Yuki Akiyoshi, PhD	Dr. Akiyoshi has received personal compensation for serving as an employee of SNBL, Ltd.. Dr. Akiyoshi has received personal compensation for serving as an employee of Tour de Medication, Ltd.. Dr. Akiyoshi has stock in SNBL, Ltd..
Chizu Date	Ms. Date has received personal compensation for serving as an employee of SNLD, Ltd., Japan. Ms. Date has received personal compensation for serving as an employee of Shin NIppon Biomedical Laboratories, Ltd., Japan.
Satoshi Nakano	Mr. Nakano has received personal compensation for serving as an employee of SNLD, Ltd., Japan. Mr. Nakano has received personal compensation for serving as an employee of Shin Nippon Biomedical Laboratories, Ltd., Japan.
Ryosuke Suzuki	Mr. Suzuki has received personal compensation for serving as an employee of SNLD, Ltd., Japan. Mr. Suzuki has received personal compensation for serving as an employee of Shin Nippon Biomedical Laboratories, Ltd., Japan.

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