BI 409306 in Patients With Cognitive Impairment Due to Alzheimer's Disease.

Study Overview
=================
Brief Summary
-----------------
The study is designed to compare the effects of BI 409306 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease

Official Title
-----------------
A Multi-centre, Double-blind, Parallel-group, Randomised Controlled Study to Investigate Efficacy, Safety and Tolerability of Orally Administered BI 409306 During a 12-week Treatment Period Compared to Placebo in Patients With Cognitive Impairment Due to Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Placebo
* Drug: BI 409306
* Drug: Donepezil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Patients with early signs of dementia of Alzheimer Type Male and female patients with an age of at least 55 years Previous use of Alzheimer's Disease (AD) medications (AChEIs, memantine) is allowed up 3 month prior to screening. 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 currently taking memantine are excluded. 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 or, if applicable, a legal representative) Exclusion criteria: Cognitive impairment or dementia with any etiology other than Alzheimer's Disease (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 Any other psychiatric disorders such as schizophrenia, or mental retardation Previous participation in investigational drug studies of mild cognitive impairment/Dementia of Alzheimer Type (DAT) within three months prior to screening. Having received active treatment in any other study targeting disease modification of AD like Aß immunization and tau therapies. 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.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo comparator<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: Placebo<br> <br> |
| Experimental: BI 409306 dose 1<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: BI 409306<br> <br> |
| Experimental: BI 409306 dose 2<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: BI 409306<br> <br> |
| Experimental: BI 409306 dose 3<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: BI 409306<br> <br> |
| Active Comparator: Active Comparator Donepezil<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: Donepezil<br> <br> |
| Experimental: BI 409306 dose 4<br> | Drug: Placebo<br>* for blinding purposes<br>Drug: BI 409306<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Least Squares Mean is actually an adjusted mean change from baseline. | Baseline and 12 weeks | 
| Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Sister Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907) | Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. The number of low test scores decreased with higher levels of intellectual abilities. Least Squares Mean is actually an adjusted mean change from baseline. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | Alzheimer's Disease Cooperative Study/Activities of Daily Living (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 can range from 0 to 78. Higher scores indicate better function. Least Squares Mean is actually an adjusted mean change from baseline. | Baseline and 12 weeks | 
| Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline. | Baseline and 12 weeks | 
| Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | Alzheimer's Disease Assessment Scale-cognitive subscale (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. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline. | Baseline and 12 weeks |