Evaluation of Montelukast Sodium as a Disease-Modifying Agent in Early to Moderate Parkinson's Disease: A Double-Blind, Randomized, Placebo-Controlled Phase II Trial

The primary objective of this study is to evaluate the effect of **Montelukast** on disease progression in patients with early to moderate **Parkinson's disease**. This is clinically relevant as it aims to determine whether Montelukast can modify the course of the disease, potentially offering a new therapeutic approach for managing Parkinson's disease.

Secondary objectives include:

• Examining the effect of Montelukast on non-motor symptoms in early to moderate Parkinson's disease.
• Assessing whether participants receiving Montelukast experience more frequent adverse events, changes in vital signs, and/or clinical laboratory values compared to those in the placebo group.
• Evaluating changes in dopaminergic treatment, as measured by the Levodopa Equivalent Daily Dose (LEDD), between baseline and the last visit.

The clinical trial focuses on individuals diagnosed with **Parkinson's disease**, specifically targeting those in the early to moderate stages of the condition. The study population includes both male and female participants, aged between 35 and 80 years. Participants are required to have a clinical diagnosis of Parkinson's disease for less than four years and must be on ongoing levodopa treatment. The trial does not involve a vulnerable population. Participants must be able to self-administer the trial drug. Female participants are required to be either post-menopausal or agree to use highly effective contraception during the trial and for three months following the last dose. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that the study population is representative of the target demographic for the investigation of Montelukast's effect on disease progression.

The clinical trial is designed as a **double-blind**, randomized, placebo-controlled phase II study to evaluate the efficacy of Montelukast as a disease-modifying treatment in patients with mild to moderate **Parkinson's disease**. The trial aims to assess the impact of Montelukast on disease progression, with a primary focus on changes in motor symptoms. The study will involve the administration of Montelukast film and a placebo, with the active substance being **montelukast sodium**. The trial is expected to last until December 31, 2026, with participant recruitment starting on September 1, 2023.

Participants will be involved in the study for a maximum of 18 months. The trial includes several key visits: an initial screening visit to confirm eligibility, baseline assessments, and follow-up visits at 6, 12, 18, and 21 months. The primary endpoint will be the change in motor symptoms, measured using the MDS-UPDRS Part 3, from baseline to month 18. Secondary endpoints include assessments of non-motor symptoms, anxiety and depression scales, and adverse events, which will be evaluated continuously throughout the study.

Inclusion criteria require participants to have a clinical diagnosis of Parkinson's disease, be between 35 and 80 years of age, and have an H&Y stage ≤ 2 in the OFF-medication state. Participants must also be on ongoing **levodopa** treatment and able to self-administer the trial drug. Female participants must adhere to specific contraceptive guidelines. Conditions for early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety.

The clinical trial involves the administration of **Madopark 100 mg/25 mg tablets**, which contain the active substances **benserazide hydrochloride** and **levodopa**. These tablets are manufactured by Roche AB and are classified under the ATC code N04BA02, indicating their use as a **levodopa and decarboxylase inhibitor**. The pharmaceutical form is a tablet, and the route of administration is oral. The maximum daily dose is 1800 mg, with a total maximum dose of 1314000 mg over a treatment period of up to 24 months. The trial monitors participant compliance with the dosing schedule to ensure accurate assessment of the medication's effects.

Another treatment used in the trial is **Montelukast film**, which contains the active substance **montelukast sodium**. This product is provided by Karolinska and is also in tablet form. The administration route is buccal, allowing the medication to be absorbed through the mucous membranes in the mouth. The maximum daily dose for Montelukast is 60 mg, with a total maximum dose of 60 mg over a treatment period of up to 18 months. The trial includes measures to monitor participant adherence to the dosing regimen.

The study also includes a **Montelukast 30 mg placebo buccal film** as a comparator treatment. This placebo is designed to mimic the appearance and administration route of the active Montelukast film but does not contain any active pharmaceutical ingredients. The use of a placebo allows for a double-blind, randomized, placebo-controlled trial design, which is essential for assessing the efficacy of Montelukast in modifying disease progression in mild to moderate Parkinson's disease.

Efficacy in the clinical trial titled "Montelukast buccal film as disease modifying treatment in mild-moderate Parkinson’s disease (MONTPARK)" will be assessed using several parameters. The primary endpoint is the measurement of motor symptoms using the **MDS-UPDRS Part 3** scale, which will be collected in the OFF-medication state at baseline, and at 6-, 12-, 18-, and 21-month visits. The primary outcome will be the model-adjusted estimate for change in motor symptom score from baseline to month 18 across each group.

Secondary endpoints include the evaluation of non-motor symptoms using the **MDS-NMS** and the **HADS** scales, assessed at baseline, and at 6-, 12-, 18-, and 21-month visits. Additionally, adverse events will be evaluated continuously throughout the trial. The **LEDD** score will be calculated at baseline and at 18 months to assess changes in levodopa equivalent daily dose. These assessments will provide a comprehensive evaluation of the efficacy of Montelukast in modifying disease progression in patients with early to moderate Parkinson's disease.