Alzheimer Disease
Conditions
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
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | Baseline and 12 weeks | 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. |
| 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) | Baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | Baseline and 12 weeks | 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. |
| Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | Baseline and 12 weeks | 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. |
| Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | Baseline and 12 weeks | 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. |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Portugal, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase II, multi-centre, double-blind, parallel-group, randomised, placebo controlled trial with patients with mild Alzheimer's disease. The randomisation allocation ratio was 1:1:1:1:2 of 10 milligram (mg), 25 mg, 50 mg once daily (QD), 25 mg twice a day (BID) of BI 409306 and placebo respectively.
Pre-assignment details
All patients were screened for eligibility. All patients eligible after screening underwent a 2-week single-blind placebo run-in period before randomisation. Patients were not to be randomized to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks. | 55 |
| BI 409306 25 mg QD Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks. | 53 |
| BI 409306 50 mg QD Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks. | 55 |
| BI 409306 25 mg Twice Daily (BID) Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks. | 55 |
| Placebo Matching BI 409306 Patients were administered orally tablet of Placebo matching BI 409306 once daily for 12 weeks. | 106 |
| Donepezil QD Patients were administered orally over capsulated tablet of Donepezil once daily for 12 weeks. | 5 |
| Total | 329 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 1 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other than listed | 1 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 | 2 | 5 | 0 |
Baseline characteristics
| Characteristic | BI 409306 10 Milligram (mg) Once Daily (QD) | BI 409306 25 mg QD | BI 409306 50 mg QD | BI 409306 25 mg Twice Daily (BID) | Placebo Matching BI 409306 | Donepezil QD | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.7 Years STANDARD_DEVIATION 8.4 | 74.2 Years STANDARD_DEVIATION 7.8 | 73.0 Years STANDARD_DEVIATION 6.5 | 74.8 Years STANDARD_DEVIATION 9.1 | 74.0 Years STANDARD_DEVIATION 7.7 | 79.6 Years STANDARD_DEVIATION 7 | 74.0 Years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 1 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 51 Participants | 51 Participants | 53 Participants | 104 Participants | 4 Participants | 316 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 53 Participants | 54 Participants | 55 Participants | 103 Participants | 5 Participants | 324 Participants |
| Sex: Female, Male Female | 26 Participants | 30 Participants | 26 Participants | 30 Participants | 48 Participants | 3 Participants | 163 Participants |
| Sex: Female, Male Male | 29 Participants | 23 Participants | 29 Participants | 25 Participants | 58 Participants | 2 Participants | 166 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 55 | 0 / 53 | 0 / 55 | 0 / 55 | 0 / 106 | 0 / 5 |
| other Total, other adverse events | 6 / 55 | 9 / 53 | 7 / 55 | 2 / 55 | 8 / 106 | 1 / 5 |
| serious Total, serious adverse events | 1 / 55 | 3 / 53 | 1 / 55 | 3 / 55 | 8 / 106 | 0 / 5 |
Outcome results
Primary
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.
Time frame: Baseline and 12 weeks
Population: The full analysis set (FAS): FAS includes all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one post-baseline on-treatment primary endpoint NTB or secondary endpoint assessment. Observed cases (OC)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.13 Z-score | Standard Error 0.059 |
| BI 409306 25 mg QD | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.17 Z-score | Standard Error 0.061 |
| BI 409306 50 mg QD | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.16 Z-score | Standard Error 0.056 |
| BI 409306 25 mg Twice Daily (BID) | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.01 Z-score | Standard Error 0.06 |
| Pooled BI 409306 | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.12 Z-score | Standard Error 0.3 |
| Placebo Matching BI 409306 | Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. | 0.15 Z-score | Standard Error 0.045 |
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.790795% CI: [-0.163, 0.124]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.762295% CI: [-0.125, 0.171]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.878995% CI: [-0.13, 0.152]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.060995% CI: [-0.285, 0.006]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.568795% CI: [-0.135, 0.074]Mixed Model Repeated Measurement (MMRM)
Primary
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.
Time frame: Baseline and 12 weeks
Population: FAS (OC) and for pooled group FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) | 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) | 0.20 Z-score | Standard Error 0.046 |
| BI 409306 25 mg QD | 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) | 0.19 Z-score | Standard Error 0.048 |
| BI 409306 50 mg QD | 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) | 0.19 Z-score | Standard Error 0.046 |
| BI 409306 25 mg Twice Daily (BID) | 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) | 0.10 Z-score | Standard Error 0.047 |
| Pooled BI 409306 | 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) | 0.17 Z-score | Standard Error 0.025 |
| Placebo Matching BI 409306 | 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) | 0.19 Z-score | Standard Error 0.035 |
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.p-value: 0.869495% CI: [-0.101, 0.12]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.p-value: 0.951295% CI: [-0.116, 0.109]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.p-value: 0.932195% CI: [-0.105, 0.115]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.p-value: 0.128895% CI: [-0.199, 0.025]Mixed Model Repeated Measurement (MMRM)
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction. The study identifier is also a categorical covariate for the twin studies analyses.p-value: 0.649295% CI: [-0.098, 0.061]Mixed Model Repeated Measurement (MMRM)
Secondary
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.
Time frame: Baseline and 12 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) | Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | 1.14 Unit on scale | Standard Error 0.738 |
| BI 409306 25 mg QD | Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | 0.94 Unit on scale | Standard Error 0.776 |
| BI 409306 50 mg QD | Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | 1.11 Unit on scale | Standard Error 0.746 |
| BI 409306 25 mg Twice Daily (BID) | Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | 2.29 Unit on scale | Standard Error 0.746 |
| Pooled BI 409306 | Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment | -0.18 Unit on scale | Standard Error 0.568 |
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.159595% CI: [-0.52, 3.15]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.245595% CI: [-0.77, 3.01]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.173295% CI: [-0.57, 3.13]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.008895% CI: [0.63, 4.31]ANCOVA
Secondary
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.
Time frame: Baseline and 12 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) | Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | 0.10 Unit on scale | Standard Error 0.853 |
| BI 409306 25 mg QD | Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | -0.99 Unit on scale | Standard Error 0.892 |
| BI 409306 50 mg QD | Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | 0.35 Unit on scale | Standard Error 0.847 |
| BI 409306 25 mg Twice Daily (BID) | Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | -1.07 Unit on scale | Standard Error 0.855 |
| Pooled BI 409306 | Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment | -0.58 Unit on scale | Standard Error 0.639 |
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.528795% CI: [-1.43, 2.77]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.710595% CI: [-2.57, 1.76]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.382295% CI: [-1.16, 3.03]ANCOVA
Comparison: The dependent variable was the change from the baseline score at Week 12. The model included fixed, categorical covariates of treatment as well as fixed continuous covariates of baseline score.p-value: 0.647295% CI: [-2.59, 1.61]ANCOVA
Secondary
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.
Time frame: Baseline and 12 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 10 Milligram (mg) Once Daily (QD) | Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | 0.1 Unit on scale | Standard Error 0.23 |
| BI 409306 25 mg QD | Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | 0.3 Unit on scale | Standard Error 0.23 |
| BI 409306 50 mg QD | Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | 0.1 Unit on scale | Standard Error 0.21 |
| BI 409306 25 mg Twice Daily (BID) | Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | 0.2 Unit on scale | Standard Error 0.22 |
| Pooled BI 409306 | Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment | 0.1 Unit on scale | Standard Error 0.16 |
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.755195% CI: [-0.46, 0.64]Mixed-effects Model for Repeated Measure
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.364395% CI: [-0.29, 0.8]Mixed-effects Model for Repeated Measure
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.782295% CI: [-0.45, 0.6]Mixed-effects Model for Repeated Measure
Comparison: Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, current Acetylcholine Esterase Inhibitor (AChEI) use (Yes, No), and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.p-value: 0.688995% CI: [-0.43, 0.65]Mixed-effects Model for Repeated Measure