BI 425809 in Patients With Cognitive Impairment Due to Alzheimer's Disease.

Study Overview
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Brief Summary
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The study is designed to compare the effects of BI 425809 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease.

Official Title
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A Multi-centre, Double-blind, Parallel-group, Randomised Controlled Study to Investigate Efficacy and Safety of Orally Administered BI 425809 During a 12-week Treatment Period Compared to Placebo in Patients With Cognitive Impairment Due to Alzheimer's Disease.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: BI 425809 dose 1
* Drug: BI 425809 dose 2
* Drug: BI 425809 dose 3
* Drug: BI 425809 dose 4
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with early signs of dementia of Alzheimer Type Male and female patients with an age of at least 55 years Concomitant use of acetylcholinesterase inhibitors (AChEIs) is allowed but not required. Patients who are currently taking AChEIs are eligible as long as they have been using a stable dose for at least 3 months prior to screening and no change is foreseen for the duration of the study. This dose must be consistent with the product label in the concerned country. Patients who are not currently taking AChEIs but have taken them in the past are also eligible if AChEIs were stopped at least 3 months prior to screening. Patients must have at least 6 years of formal education and fluency in the test language as verbally confirmed by the patient and documented by the study investigator. Patients must have a reliable study partner (per investigator judgement, for instance a family member, partner etc., guardian) Further inclusion criteria apply Exclusion criteria: Cognitive impairment or dementia with any etiology other than Alzheimer's Dementia (AD) Substantial concomitant cerebrovascular disease (defined by a history of a stroke / intracranial haemorrhagia) temporally related to the onset of worsening of cognitive impairment per investigator judgement Medical history or diagnosis of any of symptomatic and unstable/uncontrolled conditions per investigator judgement Patients receiving prescribed drugs for treatment of dementia of Alzheimer Type (other than Acetylcholine Esterase Inhibitors) at screening or within 3 months prior to screening Previous participation in investigational drug studies of dementia of Alzheimer's Type within three months prior to screening. Patients having received any active treatment in studies targeting disease modification of AD are excluded. Previous participation in studies with non-prescription medications, vitamins or other nutritional formulations is allowed. Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed. Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 425809 dose 1<br> | Drug: BI 425809 dose 1<br> <br> Drug: Placebo<br> <br> |
| Experimental: BI 425809 dose 2<br> | Drug: BI 425809 dose 2<br> <br> Drug: Placebo<br> <br> |
| Experimental: BI 425809 dose 3<br> | Drug: BI 425809 dose 3<br> <br> Drug: Placebo<br> <br> |
| Experimental: BI 425809 dose 4<br> | Drug: BI 425809 dose 4<br> <br> Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 Item (ADAS-Cog11) Total Score After 12 Weeks of Treatment | The ADAS-Cog11 is an 11-item cognitive subscale that objectively measures memory, language, orientation and praxis with a total score range of 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline. Multiple comparison procedures and modelling (MCPmod) in combination with mixed model repeated measures (MMRM) is used for primary analysis of the primary endpoint. MMRM included fixed, categorical covariates of treatment, visit, baseline Mini Mental State Examination MMSE (>=20, <20) and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline and baseline-by-visit interaction. Patient was considered as random effect. The unstructured covariance structure was used to model the within patient measurements. The same MMRM model used in the primary analysis is used for the secondary analysis of the primary endpoint. | On day 1 (visit 2, baseline) and day 85 (end of trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Score After 12 Weeks of Treatment | Change from baseline in the ADCS-ADL score after 12 weeks of treatment is presented. The ADCS-ADL is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver. Each item has a score range varying from 0-3 to 0-5. The sum score could range from 0 to 78, with higher scores indicating less severe impairment. A positive change indicates an improvement from baseline. Abbreviation: MMSE = Mini Mental State Examination | On day 1 (visit 2, baseline) and day 85 (end of trial) | 
| Clinician's Interview-Based Impression of Change (CIBIC+) Score After 12 Weeks of Treatment | Clinician's Interview-Based Impression of Change (CIBIC+) score is based on semi-structured interview covering domains of function and cognition. It additionally requires the assessment of psychiatric signs and symptoms. The patient and their caregiver are interviewed and questioned by the clinician. Change rate is based on an unanchored 7-point scale (with 0 being not assessed, 1-3 being very much improved to minimally improved, 4 being no change, and 5-7 being minimally worse to very much worse). For the ANCOVA model, the baseline value for CIBIC+ is represented by CIBIS which is clinician's interview-based impression of severity score (scores range from 0-7, with 0 being not assessed, 1 being normal, and 7 being most extremely ill) in order to adjust for potential baseline heterogeneity. Abbreviation: MMSE = Mini Mental State Examination | On day 1 (visit 2, baseline) and day 85 (end of trial) |