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

A Randomized Phase IIa, Multi-center, Double-blind, Placebo-controlled Study to Assess the Safety, Feasibility, Tolerability, and Efficacy of a New Buccal Film of Montelukast in Patients With Mild to Moderate Alzheimer's Disease

The aim of this study is to evaluate the safety, feasibility, tolerability and efficacy of a new buccal film of montelukast in patients with mild to moderate Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Montelukast buccal film; Other: Placebo buccal film

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Frank A Pietrantonio, PhD; Phone Number: 238 514-331-7440; Email: Frank@intelgenx.com
• Study Contact Backup: Name: Nadine Paiement, MSc; Phone Number: 205 514-331-7440; Email: Nadine@intelgenx.com

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • Centricity Research (formerly True North Clinical Research)
    • New Minas, Nova Scotia, Canada, B4N 3R7
      • Centricity Research (formerly True North Clinical Research)
  • Ontario
    • Ottawa, Ontario, Canada, K1N 5C8
      • Bruyère Research Institute
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Recherches Neuro-Hippocampe
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M6A 2E1
      • Baycrest
    • Toronto, Ontario, Canada, M4G 3E8
      • Gerontion Research Inc.
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Recherche Neuro-Hippocampe
    • Québec, Quebec, Canada, G1J 1Z4
      • Centre hospitalier universitaire de Québec -Université Laval
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • DIEX Recherche Sherbrooke Inc.
    • Sherbrooke, Quebec, Canada, J1J 3H5
      • Centre de recherche sur le vieillissement, CIUSSS de l'Estrie-CHUS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Montelukast buccal film, administered 10-mg once or 30-mg twice daily (once in the morning and once in the evening) for 26 weeks.	Drug: Montelukast buccal film; Film with active investigational product (montelukast) inserted and applied on inner cheek
Placebo Comparator: Group B; Placebo buccal film, administered once or twice daily (once in the morning and once in the evening) for 26 weeks.	Other: Placebo buccal film; Film with placebo (no active drug) inserted and applied on inner cheek

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Neuropsychological test battery (NTB) Composite	Evaluate if treatment with montelukast new buccal film is superior to placebo, assessed at Week 26 using the global NTB composite score. The NTB score will be used to assess cognitive and behavioral functions including problem-solving and conceptualization. The composite score will be based on an equally weighted average of standardized change from baseline scores on the following tests: International Shopping List Test (ISLT), ISLT-Delay, One Back Test, One Card Learning Test, Verbal Fluency Test, Category Fluency Test, Identification Test and Detection Test.	To be conducted at Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12) and Visit 8 (Week 26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Neuropsychological test battery (NTB) Composite	Evaluate whether 6 and 12 weeks treatment with montelukast is superior to placebo, assessed using the global NTB composite scores. The NTB score will be used to assess cognitive and behavioral functions including problem-solving and conceptualization. he composite score will be based on an equally weighted average of standardized change from baseline scores on the following tests: International Shopping List Test (ISLT), ISLT-Delay, One Back Test, One Card Learning Test, Verbal Fluency Test, Category Fluency Test, Identification Test and Detection Test	To be conducted at Visit 4 (Week 6) and Visit 6 (Week 12)
Mini Mental State Examination (MMSE)	Evaluate whether 26 weeks of treatment with montelukast improved scores using the MMSE. The MMSE will be used to assess the subject's mental status in terms of cognitive function and level of dementia. The MMSE test will consist of an 11-question measure that will test five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The maximum score is 30.	To be conducted at Visit 1 (Screening), Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12), Visit 8 (Week 26)
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	Evaluate whether 26 weeks of treatment with montelukast improved scores using the ADCS-CGIC. ADCS-CGIC assessment and rating will be based on investigator's observation of changes in the subject's cognitive, functional, and behavioral performance since the beginning of a clinical trial (baseline) until end of treatment (Week 8).	To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)
Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-items scale (ADCS-ADL23)	Evaluate whether 26 weeks of treatment with montelukast improved scores using the ADCS-ADL23. The ADCS-ADL23 outcome measurement along with the assistance of the caregiver, will measure and evaluate the change from baseline and at Week 8, in the competence and performance of the subject in conducting their basic tasks and instrumental activities of daily living.	To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)
Neuropsychiatric Inventory (NPI)	Evaluate whether 26 weeks of treatment with montelukast improves the behavioral disturbance in patients, measured by the neuropsychiatric inventory (NPI), compared to placebo. NPI is an assessment of the frequency and severity of behavioral disturbances in dementia. The inventory comprises 10 behavioural areas: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviour; and 2 neurovegetative areas. Each area has a screening question between 7 and 9 follow-up questions relating to symptoms, asked if the answer to the screening question was 'yes'. Ratings will be based on frequency, severity and distress on identified behaviours. The change from Baseline and at 26 week treatment will be measured.	To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)
Sheehan Suicide Tracking Scale (S-STS)	Evaluate whether 26 weeks of treatment with montelukast affected suicidal risk, measured by the S-STS.	To be conducted at all visits i.e., Visit 1 (Screening), Visit 2 (Baseline), Visit 3 (Week 3), Visit 4 (Week 6),Visit 5 (Week 9), Visit 6 (Week 12), Visit 7 (Week 18), and Visit 8 (Week 26)
Incontinency Frequency Rating	Evaluate whether 26 weeks of treatment with montelukast improved bladder incontinence in patients who reported this problem, measured by recording events and observations in the incontinency frequency rating.	If there is a known history of incontinence, ratings to be conducted at all visits i.e., Visit 1 (Screening), Visit 2 (Baseline), Visit 3 (Week 3), Visit 4 (Week 6),Visit 5 (Week 9), Visit 6 (Week 12), Visit 7 (Week 18), and Visit 8 (Week 26)
Incidence of Treatment-Emergent Adverse Events	Clinical safety and tolerability of montelukast film will be assessed up to Week 26 by adverse event monitoring (as assessed by CTCAE v5.0).	26 Weeks

Collaborators and Investigators

• Sponsor: IntelGenx Corp.
• Investigators: Study Director: Frank A Pietrantonio, PhD, IntelGenx Corp.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Actual): March 13, 2024
• Study Completion (Actual): April 3, 2024

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: IGX-CLI-2017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No