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
Overview
- Phase
- Phase 2
- Intervention
- Montelukast buccal film
- Conditions
- Alzheimer Disease
- Sponsor
- IntelGenx Corp.
- Enrollment
- 52
- Locations
- 11
- Primary Endpoint
- Global Neuropsychological test battery (NTB) Composite
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
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.
Investigators
Eligibility 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
Arms & Interventions
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.
Intervention: Montelukast buccal film
Group B
Placebo buccal film, administered once or twice daily (once in the morning and once in the evening) for 26 weeks.
Intervention: Placebo buccal film
Outcomes
Primary Outcomes
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 Outcomes
- Mini Mental State Examination (MMSE)(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)(To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26))
- Global Neuropsychological test battery (NTB) Composite(To be conducted at Visit 4 (Week 6) and Visit 6 (Week 12))
- Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-items scale (ADCS-ADL23)(To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26))
- Neuropsychiatric Inventory (NPI)(To be conducted at Visit 2 (Baseline) and Visit 8 (Week 26))
- Sheehan Suicide Tracking Scale (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(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(26 Weeks)