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Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02240693
Recruitment Status : Completed
First Posted : September 16, 2014
Results First Posted : November 28, 2018
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Alzheimer Disease
Interventions Drug: BI 409306
Drug: Placebo
Enrollment 128
Recruitment Details A multi-centre, double-blind, parallel-group, randomized controlled study to investigate the efficacy, safety and tolerability of orally administered BI 409306 during a 12-week treatment period compared to placebo in patients with Alzheimer's Disease
Pre-assignment Details For this trial, patients were randomised at 36 sites in 11 countries. Following an initial Screening Visit and a single blinded 2-week placebo run-in period, patients who qualified according to the in- and exclusion criteria were randomised to one of the five treatment groups
Arm/Group Title 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
Hide Arm/Group Description Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks. Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Period Title: Overall Study
Started 22 21 21 21 43
Completed 22 21 17 20 42
Not Completed 0 0 4 1 1
Reason Not Completed
Adverse Event             0             0             0             0             1
Withdrawal by Subject             0             0             2             1             0
Other than specified             0             0             2             0             0
Arm/Group Title 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 Total
Hide Arm/Group Description Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks. Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 22 21 21 21 43 128
Hide Baseline Analysis Population Description
Treated set: The treated set (TS) included all patients who were randomised and treated with at least one dose of trial medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 21 participants 21 participants 21 participants 43 participants 128 participants
72.3  (5.4) 74.1  (8.1) 73.3  (5.1) 71.9  (6.0) 72.2  (6.5) 72.7  (6.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 21 participants 21 participants 43 participants 128 participants
Female
10
  45.5%
12
  57.1%
8
  38.1%
13
  61.9%
28
  65.1%
71
  55.5%
Male
12
  54.5%
9
  42.9%
13
  61.9%
8
  38.1%
15
  34.9%
57
  44.5%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 21 participants 21 participants 21 participants 43 participants 128 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
22
 100.0%
21
 100.0%
21
 100.0%
21
 100.0%
43
 100.0%
128
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Race data is presented below; Ethnicity was not reported in this trial
Neuropsychological Test Battery (NTB) Total   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-score
Number Analyzed 22 participants 21 participants 21 participants 21 participants 43 participants 128 participants
0.07  (0.70) 0.02  (0.75) -0.02  (0.72) -0.02  (0.61) -0.03  (0.63) -0.00  (0.66)
[1]
Measure Description: Baseline cognitive assessment data- NTB total z-score. 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. Higher values indicate a better Outcome
1.Primary Outcome
Title Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.
Hide Description Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. 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. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included 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 efficacy assessment. Observed cases (OC)
Arm/Group Title 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) Pooled BI 409306 Placebo Matching BI 409306
Hide Arm/Group Description:
Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.
Patients were administered orally a tablet of BI 409306 (10 mg, 25 mg, 50 mg once daily and 25 mg twice daily)for 12 weeks.
Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Overall Number of Participants Analyzed 20 19 16 18 73 39
Least Squares Mean (Standard Error)
Unit of Measure: z-score
0.35  (0.061) 0.20  (0.063) 0.26  (0.065) 0.32  (0.064) 0.29  (0.031) 0.27  (0.043)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 409306 10 Milligram (mg) Once Daily (QD), Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.3236
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.074 to 0.223
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.075
Estimation Comments Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg QD, Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.3694
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.220 to 0.082
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.076
Estimation Comments Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BI 409306 50 mg QD, Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.8374
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.171 to 0.139
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.078
Estimation Comments Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg Twice Daily (BID), Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.5484
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.106 to 0.199
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.077
Estimation Comments Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled BI 409306, Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.7905
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.092 to 0.121
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.054
Estimation Comments Mean difference (Pooled BI 409306 minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
2.Primary Outcome
Title Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Twin Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)
Hide Description Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. 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. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS observed cases for pooled groups of these twin trials
Arm/Group Title 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) Pooled BI 409306 Placebo Matching BI 409306
Hide Arm/Group Description:
Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.
Patients were administered orally a tablet of BI 409306 (10 mg, 25 mg, 50 mg once daily and 25 mg twice daily)for 12 weeks.
Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Overall Number of Participants Analyzed 67 63 67 63 260 122
Least Squares Mean (Standard Error)
Unit of Measure: z-score
0.20  (0.046) 0.19  (0.048) 0.19  (0.046) 0.10  (0.047) 0.17  (0.025) 0.19  (0.035)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 409306 10 Milligram (mg) Once Daily (QD), Placebo Matching BI 409306
Comments

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.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.8694
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.101 to 0.120
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.056
Estimation Comments Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg QD, Placebo Matching BI 409306
Comments

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.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.9512
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.116 to 0.109
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.057
Estimation Comments Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BI 409306 50 mg QD, Placebo Matching BI 409306
Comments

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.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.9321
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.105 to 0.115
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.056
Estimation Comments Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg Twice Daily (BID), Placebo Matching BI 409306
Comments

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.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.1288
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.199 to 0.025
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.057
Estimation Comments Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pooled BI 409306, Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments H0: The dose group with the peak response in the respective model Mean NTB response = Mean NTB response of placebo.
Statistical Test of Hypothesis P-Value 0.6492
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.098 to 0.061
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.041
Estimation Comments Mean difference (Pooled BI 409306 minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
3.Secondary Outcome
Title Change From Baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) Total Score After 12-week Treatment
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS- Observed cases
Arm/Group Title 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
Hide Arm/Group Description:
Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.
Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Overall Number of Participants Analyzed 19 18 20 17 37
Least Squares Mean (Standard Error)
Unit of Measure: Unit on scale
0.24  (0.896) 1.79  (0.921) -0.10  (0.875) 0.80  (0.947) 0.38  (0.642)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 409306 10 Milligram (mg) Once Daily (QD), Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.8973
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-2.33 to 2.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.102
Estimation Comments Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg QD, Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.2141
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
-0.82 to 3.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.122
Estimation Comments Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BI 409306 50 mg QD, Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.6553
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-2.64 to 1.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.085
Estimation Comments Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg Twice Daily (BID), Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.7166
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-1.85 to 2.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.144
Estimation Comments Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
4.Secondary Outcome
Title Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS- Observed cases
Arm/Group Title 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
Hide Arm/Group Description:
Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.
Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Overall Number of Participants Analyzed 21 19 16 18 40
Least Squares Mean (Standard Error)
Unit of Measure: Unit on scale
0.0  (0.19) 0.4  (0.20) -0.1  (0.22) 0.1  (0.21) 0.1  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 409306 10 Milligram (mg) Once Daily (QD), Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9491
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.49 to 0.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.24
Estimation Comments Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg QD, Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1699
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.15 to 0.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.25
Estimation Comments Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BI 409306 50 mg QD, Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4948
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.69 to 0.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.26
Estimation Comments Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg Twice Daily (BID), Placebo Matching BI 409306
Comments Mixed Model Repeated Measurement (MMRM) includes fixed, categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous fixed covariates of baseline, and baseline-by-visit interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7548
Comments p-value was nominal and not adjusted.
Method Mixed Model Repeated Measurement (MMRM)
Comments Kenward-Roger was used to model degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.42 to 0.58
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.25
Estimation Comments Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
5.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS- Observed cases
Arm/Group Title 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
Hide Arm/Group Description:
Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks.
Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks.
Patients were administered orally Placebo matching 10 mg/25 mg/ 50 mg BI 409306 for 12 weeks
Overall Number of Participants Analyzed 19 17 19 19 38
Least Squares Mean (Standard Error)
Unit of Measure: Unit on scale
0.98  (0.885) 0.62  (0.935) 0.12  (0.875) -1.27  (0.875) 1.24  (0.619)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 409306 10 Milligram (mg) Once Daily (QD), Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.8137
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-2.40 to 1.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.081
Estimation Comments Mean difference (BI 409306 10 milligram (mg) once daily (QD) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg QD, Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.5801
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-2.84 to 1.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.120
Estimation Comments Mean difference (BI 409306 25 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BI 409306 50 mg QD, Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.2978
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.12
Confidence Interval (2-Sided) 95%
-3.25 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.072
Estimation Comments Mean difference (BI 409306 50 mg QD minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BI 409306 25 mg Twice Daily (BID), Placebo Matching BI 409306
Comments 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.
Type of Statistical Test Superiority
Comments Analyses of covariance (ANCOVA) were used to assess between-group differences in the modelled changes from baseline to Week 12.
Statistical Test of Hypothesis P-Value 0.0209
Comments p-value was nominal and not adjusted.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.51
Confidence Interval (2-Sided) 95%
-4.64 to -0.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.072
Estimation Comments Mean difference (BI 409306 25 mg twice daily (BID) minus Placebo matching BI 409306)
Other Statistical Analysis The mean difference is actually adjusted mean of difference and the dispersion value is standard error of differences
Time Frame From the first dose of study medication until 7 days after last administration of BI 409306, up to 16 weeks.
Adverse Event Reporting Description The treated set (TS) used (all patients who were randomised and treated with at least one dose of trial medication.) for safety assessment.
 
Arm/Group Title 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
Hide Arm/Group Description Patients were administered orally a tablet of 10 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 50 mg BI 409306 once daily for 12 weeks. Patients were administered orally a tablet of 25 mg BI 409306 twice daily for 12 weeks. Patients were administered orally tablet of Placebo matching BI 409306 once daily for 12 weeks.
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/21 (0.00%)   0/21 (0.00%)   0/21 (0.00%)   0/43 (0.00%) 
Hide Serious Adverse Events
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/21 (0.00%)   0/21 (0.00%)   1/21 (4.76%)   1/43 (2.33%) 
Gastrointestinal disorders           
Abdominal pain † 1  0/22 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/43 (2.33%) 
Renal and urinary disorders           
Haematuria † 1  0/22 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/21 (4.76%)  0/43 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/22 (22.73%)   8/21 (38.10%)   11/21 (52.38%)   3/21 (14.29%)   6/43 (13.95%) 
Cardiac disorders           
Bradycardia † 1  2/22 (9.09%)  3/21 (14.29%)  1/21 (4.76%)  1/21 (4.76%)  0/43 (0.00%) 
Eye disorders           
Vision blurred † 1  0/22 (0.00%)  0/21 (0.00%)  3/21 (14.29%)  0/21 (0.00%)  0/43 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back pain † 1  0/22 (0.00%)  1/21 (4.76%)  2/21 (9.52%)  0/21 (0.00%)  0/43 (0.00%) 
Muscle spasms † 1  0/22 (0.00%)  2/21 (9.52%)  0/21 (0.00%)  0/21 (0.00%)  0/43 (0.00%) 
Nervous system disorders           
Headache † 1  2/22 (9.09%)  4/21 (19.05%)  3/21 (14.29%)  0/21 (0.00%)  2/43 (4.65%) 
Skin and subcutaneous tissue disorders           
Rash † 1  0/22 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  2/21 (9.52%)  0/43 (0.00%) 
Vascular disorders           
Hypertension † 1  2/22 (9.09%)  0/21 (0.00%)  4/21 (19.05%)  0/21 (0.00%)  4/43 (9.30%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02240693    
Other Study ID Numbers: 1289.5
2013-005031-24 ( EudraCT Number )
First Submitted: September 15, 2014
First Posted: September 16, 2014
Results First Submitted: September 11, 2018
Results First Posted: November 28, 2018
Last Update Posted: November 28, 2018