Safety, and Efficacy of a New Buccal Film of Montelukast in Patients With Mild to Moderate Alzheimer's Disease

This is a randomized Phase IIa, multi-center, double-blind, placebo-controlled study of a new buccal film of montelukast in patients with mild to moderate Alzheimer's Disease. Study drug (montelukast or matching placebo) will be administered once or twice daily for 26 weeks, and treatment effect will be assessed primarily using the global NTB composite score at Week 26.

Patients who consent to participate will undergo screening assessments to determine eligibility. This study will enroll patients who are ≥50 years of age with mild to moderate Alzheimer's Disease and on a stable treatment of donepezil, rivastigmine or galantamine for ≥3 months. Patients will be randomized (using a balanced block randomization schedule) to one of two treatment groups:

• Group A: Montelukast buccal film
• Group B: Matching placebo buccal film

In addition to the global NTB composite, patients will also be evaluated using the MMSE, ADCS-CGIC, ADCS-ADL23, NPI and S-STS. Patients will be followed for any safety concerns throughout the study and for 4 weeks following the last study visit.

Inclusion criteria

• Mild to moderate Alzheimer's Disease.
• MMSE score of 14 - 22
• CT or MRI within 18 months prior to screening indicating clinical phenotype of Alzheimer's Disease
• Treated daily with donepezil, rivastigmine or galantamine for ≥ 3 months
• All other medications for chronic conditions should have been at a stable dose for at least 2 weeks prior to first dose.
• No clinically meaningful abnormalities on electrocardiogram (ECG), physical examination and clinical laboratory tests

Exclusion criteria

• Taken memantine within 2 months prior to screening.
• Current diagnosis of any psychiatric disorder, depression that is not well-controlled, clinically significant or unstable systemic disease, or severe medical procedures
• Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation.
• Patients at imminent risk of self-harm, based on clinical interview and response on S-STS
• History of malignancy occurring within 5 years immediately prior to screening, except for a subject who has been adequately treated for (1) basal cell or squamous cell skin cancer, (2) in situ cervical cancer, (3) localized prostate carcinoma, or (4) who has undergone potentially curative therapy with no evidence of recurrence for more than 3 years post-therapy, and who is deemed at low risk for recurrence by her/his treating physician
• History of any of the following cardiovascular conditions that an unstable:

• Hypotension
• Hypertension
• Active cardiovascular disease
• Evidence of cerebrovascular disease
• Have used or plan to use the following medications from 30 days prior to Visit 1 through the end of the study:

• Narcotic analgesics more frequently than on three days per week as needed for pain;
• Daily antipsychotic (except for risperidone, quetiapine and aripiprazole, and only if at a stable and controlled dose)
• Daily anxiolytic use; however, occasional use as needed for acute agitation or to be used as a rescue anxiolytic (i.e., lorazepam and oxazepam) is acceptable as long as not used within 24 hours of a clinic visit window;
• Daily antidepressants (except for citalopram, escitalopram, venlafaxine, trazodone, sertraline, and mirtazapine, and only if at a stable and controlled dose);
• Low potency antipsychotic agents (eg chlorpromazine) - not permitted at any time during the study;
• Anti-parkinson's disease medications (selegiline, levodopa, amantadine) for the treatment of Parkinson's Syndrome Complex;
• Lithium;
• Clozapine;
• Previously treated with or currently using montelukast