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

• ClinicalTrials.gov Identifier: NCT03402503
• Recruitment Status: Recruiting
• First Posted: January 18, 2018
• Last Update Posted: January 25, 2023
• Sponsor: IntelGenx Corp.
• Information provided by (Responsible Party): IntelGenx Corp.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: Montelukast buccal film; Other: Placebo buccal film	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 26, 2018
• Estimated Primary Completion Date: October 19, 2023
• Estimated Study Completion Date: December 19, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Global Neuropsychological test battery (NTB) Composite [ Time Frame: To be conducted at Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12) and Visit 8 (Week 26) ]
   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.

Secondary Outcome Measures :

1. Global Neuropsychological test battery (NTB) Composite [ Time Frame: To be conducted at Visit 4 (Week 6) and Visit 6 (Week 12) ]
   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
2. Mini Mental State Examination (MMSE) [ Time Frame: To be conducted at Visit 1 (Screening), Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12), Visit 8 (Week 26) ]
   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.
3. Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26) ]
   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).
4. Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-items scale (ADCS-ADL23) [ Time Frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26) ]
   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.
5. Neuropsychiatric Inventory (NPI) [ Time Frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26) ]
   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.
6. Sheehan Suicide Tracking Scale (S-STS) [ Time Frame: 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) ]
   Evaluate whether 26 weeks of treatment with montelukast affected suicidal risk, measured by the S-STS.
7. Incontinency Frequency Rating [ Time Frame: 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) ]
   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.
8. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 26 Weeks ]
   Clinical safety and tolerability of montelukast film will be assessed up to Week 26 by adverse event monitoring (as assessed by CTCAE v5.0).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Frank A Pietrantonio, PhD; 514-331-7440 ext 238; Frank@intelgenx.com

Contact: Nadine Paiement, MSc; 514-331-7440 ext 205; Nadine@intelgenx.com

Locations

Canada, British Columbia

Vancouver Island Health Authority; Recruiting

Victoria, British Columbia, Canada, V8R 1J8

Canada, Nova Scotia

Centricity Research (formerly True North Clinical Research); Recruiting

Halifax, Nova Scotia, Canada, B3S 1N2

Centricity Research (formerly True North Clinical Research); Recruiting

New Minas, Nova Scotia, Canada, B4N 3R7

Canada, Ontario

Bruyère Research Institute; Recruiting

Ottawa, Ontario, Canada, K1N 5C8

Recherches Neuro-Hippocampe; Recruiting

Ottawa, Ontario, Canada, K1Z 1G3

Kawartha Centre - Redefining Healthy Aging; Recruiting

Peterborough, Ontario, Canada, K9H 2P4

Gerontion Research Inc.; Completed

Toronto, Ontario, Canada, M4G 3E8

Toronto Western Hospital; Withdrawn

Toronto, Ontario, Canada, M5T 2S8

Baycrest; Recruiting

Toronto, Ontario, Canada, M6A 2E1

Canada, Quebec

Recherche Neuro-Hippocampe; Recruiting

Gatineau, Quebec, Canada, J8T 8J1

Centre hospitalier universitaire de Québec -Université Laval; Recruiting

Québec, Quebec, Canada, G1J 1Z4

Centre de recherche sur le vieillissement, CIUSSS de l'Estrie-CHUS; Recruiting

Sherbrooke, Quebec, Canada, J1J 3H5

Diex Recherche Sherbrooke Inc.; Recruiting

Sherbrooke, Quebec, Canada, J1L 0H8

Douglas Mental Health University Institute; Withdrawn

Verdun, Quebec, Canada, H4H 1R3

Canada, Saskatchewan

Pasqua Hospital; Withdrawn

Regina, Saskatchewan, Canada, S4T 1A5

Sponsors and Collaborators

IntelGenx Corp.

Investigators

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

More Information

• Responsible Party: IntelGenx Corp.
• ClinicalTrials.gov Identifier: NCT03402503
• Other Study ID Numbers: IGX-CLI-2017-001
• First Posted: January 18, 2018
• Last Update Posted: January 25, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Montelukast; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action