ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03402503
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
IntelGenx Corp.

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 (10-mg montelukast or matching placebo) will be administered once 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: 10-mg 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  (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 : July 19, 2020
Estimated Study Completion Date : October 19, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Montelukast

Arm Intervention/treatment
Experimental: Group A
Montelukast buccal film given daily 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 given daily for 26 weeks
Other: Placebo buccal film
Film with placebo (no active drug) inserted and applied on inner cheek




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 one strength of montelukast new buccal film administered once a day 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 administered once a day 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 v4.1).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

    • Daily antipsychotic or anxiolytic use (eg, lorazepam can be used as rescue anxiolytic as long as not used within 24 hours of a clinic visit);
    • 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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03402503


Contacts
Contact: F. Pietrantonio, PhD 514-331-7440 ext 217 Frank@intelgenx.com
Contact: N. 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
True North Clinical Research Recruiting
Halifax, Nova Scotia, Canada, B3S 1M7
True North Clinical Research Recruiting
Kentville, Nova Scotia, Canada, B4N 4K9
Canada, Ontario
Gerontion Research Inc. Recruiting
Toronto, Ontario, Canada, M4G 3E8
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
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
Canada, Saskatchewan
Pasqua Hospital Recruiting
Regina, Saskatchewan, Canada, S4T 1A5
Sponsors and Collaborators
IntelGenx Corp.
Investigators
Study Director: F. Pietrantonio, PhD IntelGenx Corp.

Responsible Party: IntelGenx Corp.
ClinicalTrials.gov Identifier: NCT03402503     History of Changes
Other Study ID Numbers: IGX-CLI-2017-001
First Posted: January 18, 2018    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: November 2018
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