CClinicalTrials.gg
CompletedNCT03402503BUENAUpdated Apr 18, 2024

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

A Phase 2 interventional study of Montelukast buccal film and Placebo buccal film in Alzheimer Disease, sponsored by IntelGenx Corp.. Completed at 12 sites in Canada. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2024-04-18.

Sponsored by IntelGenx Corp. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Alzheimer Disease

Browse trials for

03

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
52 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugMontelukast buccal film

    Film with active investigational product (montelukast) inserted and applied on inner cheek

  • OtherPlacebo buccal film

    Film with placebo (no active drug) inserted and applied on inner cheek

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: To be conducted at Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12) and Visit 8 (Week 26)

Secondary outcomes

  1. 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

    Time frame: To be conducted at Visit 4 (Week 6) and Visit 6 (Week 12)

  2. 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.

    Time frame: To be conducted at Visit 1 (Screening), Visit 2 (Baseline), Visit 4 (Week 6), Visit 6 (Week 12), Visit 8 (Week 26)

  3. 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).

    Time frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)

  4. 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.

    Time frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)

  5. 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.

    Time frame: To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26)

  6. Sheehan Suicide Tracking Scale (S-STS)

    Evaluate whether 26 weeks of treatment with montelukast affected suicidal risk, measured by the 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)

  7. 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.

    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)

  8. 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).

    Time frame: 26 Weeks

06

Study locations

12 sites
  • Vancouver Island Health Authority
    Victoria, British Columbia V8R 1J8, Canada
  • Centricity Research (formerly True North Clinical Research)
    Halifax, Nova Scotia B3S 1N2, Canada
  • Centricity Research (formerly True North Clinical Research)
    New Minas, Nova Scotia B4N 3R7, Canada
  • Bruyère Research Institute
    Ottawa, Ontario K1N 5C8, Canada
  • Recherches Neuro-Hippocampe
    Ottawa, Ontario K1Z 1G3, Canada
  • Kawartha Centre - Redefining Healthy Aging
    Peterborough, Ontario K9H 2P4, Canada
  • Gerontion Research Inc.
    Toronto, Ontario M4G 3E8, Canada
  • Baycrest
    Toronto, Ontario M6A 2E1, Canada
  • Recherche Neuro-Hippocampe
    Gatineau, Quebec J8T 8J1, Canada
  • Centre hospitalier universitaire de Québec -Université Laval
    Québec, Quebec G1J 1Z4, Canada
  • Centre de recherche sur le vieillissement, CIUSSS de l'Estrie-CHUS
    Sherbrooke, Quebec J1J 3H5, Canada
  • Diex Recherche Sherbrooke Inc.
    Sherbrooke, Quebec J1L 0H8, Canada
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03402503
Lead sponsor
IntelGenx Corp.
Responsible party
Sponsor
First posted
Jan 18, 2018
Start date
Nov 26, 2018
Primary completion
Mar 13, 2024
Completion
Apr 3, 2024
Last update
Apr 18, 2024

Study contacts

Frank A Pietrantonio, PhD
study director · IntelGenx Corp.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion