BI 425809 in Patients With Cognitive Impairment Due to Al... | NCT02788513 | Trialant
NCT02788513
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Nov 6, 2020Actual
Enrollment
611Actual
Phase
Phase 2
Conditions
Alzheimer Disease
Interventions
BI 425809 dose 1
BI 425809 dose 2
BI 425809 dose 3
BI 425809 dose 4
Placebo
Countries
United States
Austria
Canada
Finland
France
Germany
Greece
Hungary
Italy
Japan
Norway
Poland
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02788513
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1346.23
Secondary IDs
ID
Type
Description
Link
2015-005438-24
EudraCT Number
Brief Title
BI 425809 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 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.
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Oct 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Aug 11, 2016Actual
Primary Completion Date
Sep 12, 2019Actual
Completion Date
Oct 11, 2019Actual
First Submitted Date
May 27, 2016
First Submission Date that Met QC Criteria
May 27, 2016
First Posted Date
Jun 2, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 10, 2020
Results First Submitted that Met QC Criteria
Oct 16, 2020
Results First Posted Date
Nov 6, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 16, 2020
Last Update Posted Date
Nov 6, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study is designed to compare the effects of BI 425809 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease.
Detailed Description
Not provided
Conditions Module
Conditions
Alzheimer Disease
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
611Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
BI 425809 dose 1
Experimental
Drug: BI 425809 dose 1
Drug: Placebo
BI 425809 dose 2
Experimental
Drug: BI 425809 dose 2
Drug: Placebo
BI 425809 dose 3
Experimental
Drug: BI 425809 dose 3
Drug: Placebo
BI 425809 dose 4
Experimental
Drug: BI 425809 dose 4
Drug: Placebo
Placebo
Placebo Comparator
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
BI 425809 dose 1
Drug
BI 425809 dose 1
BI 425809 dose 2
Outcomes Module
Primary Outcomes
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 Outcomes
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
Other Outcomes
Not provided
Eligibility Module
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
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.
Wunderlich G, Blahova Z, Garcia M, Jessen F. Efficacy and safety of the novel GlyT1 inhibitor BI 425809 in Alzheimer's dementia: a randomized controlled trial. Alzheimers Res Ther. 2023 Jan 28;15(1):24. doi: 10.1186/s13195-023-01163-3.
Subjects were screened prior to participation and attended a specialist site which ensured that they strictly met all inclusion/exclusion criteria. Subjects were not to be allocated to a treatment group if any of the criteria were violated.
One subject was randomized by error via Interactive Response Technology (IRT) but never took a drug.
Recruitment Details
This is 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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
FG001
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 12, 2018
Oct 8, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
Not provided
Drug
BI 425809 dose 2
BI 425809 dose 3
Drug
BI 425809 dose 3
BI 425809 dose 4
Drug
BI 425809 dose 4
Placebo
Drug
BI 425809 dose 1
BI 425809 dose 2
BI 425809 dose 3
BI 425809 dose 4
Placebo
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)
Long Beach
California
90807
United States
Anderson Clinical Research
Redlands
California
92374
United States
CITrials
Santa Ana
California
92705
United States
MD Clinical
Hallandale
Florida
33009
United States
Galiz Research
Miami
Florida
33016
United States
Premier Clinical Research Institute
Miami
Florida
33122
United States
Miami Jewish Health System
Miami
Florida
33137
United States
Stedman Clinical Trials
Tampa
Florida
33613
United States
Bioclinica Research
The Villages
Florida
32162
United States
Neuro Trials Research Incorporated
Atlanta
Georgia
30342
United States
Millennium Psychiatric Associates LLC
St Louis
Missouri
63132
United States
ANI Neurology, PLLC, dba Alzheimer's Memory Center
Charlotte
North Carolina
28270
United States
Tulsa Clinical Research, LLC
Tulsa
Oklahoma
74104
United States
Northeastern Pennsylvania Memory and Alzheimer Center
Clin.Research Centre Clinsante SC Ewa Galczak-Nowak,Torun
Torun
87-100
Poland
Hospital del Mar
Barcelona
08003
Spain
Hospital Vall d'Hebron
Barcelona
08035
Spain
Hospital Sant Joan de Deu de Manresa
Manresa
08423
Spain
Hospital Universitari General de Catalunya
Sant Cugat del Vallès
08190
Spain
Hospital Universitario Marqués de Valdecilla
Santander
39008
Spain
Hospital Viamed Montecanal
Zaragoza
50012
Spain
Royal Cornhill Hospital
Aberdeen
AB25 2ZH
United Kingdom
Fulbourn Hospital
Cambridge
CB21 5EF
United Kingdom
Ninewells Hospital & Medical School
Dundee
DD2 1SY
United Kingdom
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
Queen Elizabeth University Hospital
Glasgow
G51 4TF
United Kingdom
Warneford Hospital
Oxford
OX3 7JX
United Kingdom
Sheffield Memory Service
Sheffield
S10 3TH
United Kingdom
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
FG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
FG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
FG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
FG000123 subjects
FG001122 subjects
FG002122 subjects
FG003123 subjects
FG004120 subjects
COMPLETED
FG000114 subjects
FG001114 subjects
FG002114 subjects
FG003117 subjects
FG004115 subjects
NOT COMPLETED
FG0009 subjects
FG0018 subjects
FG0028 subjects
FG0036 subjects
FG0045 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0003 subjects
FG0010 subjects
FG0022 subjects
FG0033 subjects
FG0041 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0005 subjects
FG0018 subjects
FG0024 subjects
FG0032 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG004
Subject decided to stop taking treatment
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Decision by the study team
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Treated set (TS): the TS included all patients treated with at least one dose of trial medication. Patients in the treated set were analysed based on the actual treatment received at the randomisation. The TS was used for safety analyses.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
BG001
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
BG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
BG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
BG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000123
BG001122
BG002122
BG003123
BG004120
BG005610
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG000123
ParticipantsBG001122
ParticipantsBG002122
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000123
ParticipantsBG001122
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000123
ParticipantsBG001122
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000123
ParticipantsBG001122
ParticipantsBG002
ADASCOG baseline cognitive assessment data
The Alzheimer's Disease Assessment Scale-Cognitive subscale 11 item (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.
Treated set (TS): the TS included all patients treated with at least one dose of trial medication. Patients in the treated set were analysed based on the actual treatment received at the randomisation. The TS was used for safety analyses. One placebo subject was without baseline measures due to study was put on hold.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG000123
ParticipantsBG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Full analysis set (FAS): all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one corresponding post-baseline on-treatment efficacy assessment for any efficacy endpoint. FAS was used for efficacy analyses.
Posted
Mean
Standard Deviation
score on a scale
On day 1 (visit 2, baseline) and day 85 (end of trial)
ID
Title
Description
OG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG001
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
Units
Counts
Participants
OG000121
OG001120
OG002121
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.026± 4.864
OG0010.175± 4.471
OG0020.699± 4.313
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
OG004
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod Beta model fit.
Model assumption: 75% of max effect is achieved at 2 mg, 87.5% at 5 mg, 25% at 25 mg, max effect achieved at 10 mg of BI 425809, scalar parameter = 26
0.9931
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
Secondary
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
Full analysis set (FAS): all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one corresponding post-baseline on-treatment efficacy assessment for any efficacy endpoint. FAS was used for efficacy analyses.
Posted
Mean
Standard Deviation
score on a scale
On day 1 (visit 2, baseline) and day 85 (end of trial)
ID
Title
Description
OG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG001
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
Secondary
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
Full analysis set (FAS): all randomised patients who were treated with at least one dose of trial medication and had a baseline and at least one corresponding post-baseline on-treatment efficacy assessment for any efficacy endpoint. FAS was used for efficacy analyses.
Posted
Mean
Standard Deviation
score on a scale
On day 1 (visit 2, baseline) and day 85 (end of trial)
ID
Title
Description
OG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
Time Frame
From first dose of study drug until end of treatment + 28 days of follow-up, up to 16 weeks.
Description
Treated set (TS): the TS included all patients treated with at least one dose of trial medication. Patients in the treated set were analysed based on the actual treatment received at the randomisation.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
2 mg BI 425809
Participants in dose group 1 were orally administered 2 tablets of 1 milligrams (mg) of BI 425809 (Total: 2 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
0
123
5
123
17
123
EG001
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
0
122
4
122
22
122
EG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
0
122
4
122
14
122
EG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
0
123
4
123
19
123
EG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
0
120
5
120
12
120
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrial flutter
Cardiac disorders
MedDRA 22.1
Systematic Assessment
EG0001 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG0030 affected123 at risk
EG0040 affected120 at risk
Cataract
Eye disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0021 affected122 at risk
EG003
Glaucoma
Eye disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0001 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Gingivitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0001 affected123 at risk
EG0010 affected122 at risk
EG0021 affected122 at risk
EG003
Sepsis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0021 affected122 at risk
EG003
Urinary tract infection bacterial
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0002 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Torticollis
Musculoskeletal and connective tissue disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0021 affected122 at risk
EG003
Pancreatic neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Dementia
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Syncope
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0001 affected123 at risk
EG0010 affected122 at risk
EG0021 affected122 at risk
EG003
Depression
Psychiatric disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0011 affected122 at risk
EG0020 affected122 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 22.1
Systematic Assessment
EG0000 affected123 at risk
EG0010 affected122 at risk
EG0020 affected122 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
MedDRA 22.1
Systematic Assessment
EG0006 affected123 at risk
EG0011 affected122 at risk
EG0022 affected122 at risk
EG0038 affected123 at risk
EG0042 affected120 at risk
Nasopharyngitis
Infections and infestations
MedDRA 22.1
Systematic Assessment
EG0003 affected123 at risk
EG0017 affected122 at risk
EG0023 affected122 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0004 affected123 at risk
EG0019 affected122 at risk
EG0023 affected122 at risk
EG003
Headache
Nervous system disorders
MedDRA 22.1
Systematic Assessment
EG0006 affected123 at risk
EG00110 affected122 at risk
EG0027 affected122 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod Emax model fit.
Model assumption: 20% of the maximum effect is achieved at 2 mg
0.9225
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
OG000
OG001
OG002
OG003
OG004
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod Sigmoidal Emax model fit.
Model assumption: 25% of max effect achieved at 5 mg and 75% of max effect achieved at 10 mg of BI 425809.
0.9287
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
OG000
OG001
OG002
OG003
OG004
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod linear model fit.
No assumption needed.
0.7646
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
OG000
OG001
OG002
OG003
OG004
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod linear in log model fit.
No assumption needed.
0.9335
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
OG000
OG001
OG002
OG003
OG004
Multiple comparison procedures and modelling (MCPmod) techniques for mixed model repeated measures (MMRM) was used.
MCPMod logistic model fit.
Model assumption: 10% of max effect achieved at 5 mg and 50% of max effect achieved at 10 mg of BI 425809.
0.8199
An alpha of 0.05 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
Other
OG000
OG004
Mixed model repeated measures (MMRM)
MMRM
MMRM information is described in the description section.
0.9340
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
0.05
Standard Error of the Mean
0.58
2-Sided
95
-1.09
1.18
Other
OG001
OG004
Mixed model repeated measures (MMRM)
MMRM
MMRM information is described in the description section.
0.6041
p-values are nominal without multiplicity adjustment.
Median Difference (Final Values)
0.30
Standard Error of the Mean
0.58
2-Sided
95
-0.84
1.44
Other
OG002
OG004
Mixed model repeated measures (MMRM)
MMRM
MMRM information is described in the description section.
0.1926
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
0.76
Standard Error of the Mean
0.58
2-Sided
95
-0.38
1.90
Other
OG003
OG004
Mixed model repeated measures (MMRM)
MMRM
MMRM information is described in the description section.
0.9739
p-values are nominal without multiplicity adjustment.
Median Difference (Final Values)
-0.02
Standard Error of the Mean
0.58
2-Sided
95
-1.16
1.12
Other
OG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
Units
Counts
Participants
OG000113
OG001111
OG002110
OG003116
OG004111
Title
Denominators
Categories
Title
Measurements
OG0000.283± 6.805
OG0010.577± 5.852
OG002-1.145± 4.764
OG003-1.828± 7.034
OG0040.261± 4.842
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
Analysis of Covariance model included baseline value for the secondary endpoint measure, MMSE stratification (>=20, <20) at baseline and treatment.
0.979
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
0.02
Standard Error of the Mean
0.76
2-Sided
95
-1.48
1.52
Other
OG001
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
Analysis of Covariance model included baseline value for the secondary endpoint measure, MMSE stratification (>=20, <20) at baseline and treatment.
0.521
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
0.49
Standard Error of the Mean
0.77
2-Sided
95
-1.01
2.00
Other
OG002
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
Analysis of Covariance model included baseline value for the secondary endpoint measure, MMSE stratification (>=20, <20) at baseline and treatment.
0.047
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
-1.53
Standard Error of the Mean
0.77
2-Sided
95
-3.04
-0.02
Other
OG003
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
Analysis of Covariance model included baseline value for the secondary endpoint measure, MMSE stratification (>=20, <20) at baseline and treatment.
0.005
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
-2.16
Standard Error of the Mean
0.76
2-Sided
95
-3.65
-0.67
Other
OG001
5 mg BI 425809
Participants in dose group 2 were orally administered 1 tablet of 5 mg of BI 425809 together with 1 tablet of 1 mg / 5 mg and 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG002
10 mg BI 425809
Participants in dose group 3 were orally administered 2 tablets of 5 mg of BI 425809 (Total: 10 mg) together with 1 tablet of 25 mg placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG003
25 mg BI 425809
Participants in dose group 4 were orally administered 1 tablet of 25 mg of BI 425809 together with 2 tablets of 1 mg / 5 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
OG004
Placebo Group
Participants in the placebo group were orally administered 2 tablets of 1 mg / 5 mg and 1 tablet of 25 mg of placebo match once daily (qd) during 12 weeks. The tablets were to be taken with water in the morning at approximately the same time every day with or without food.
Units
Counts
Participants
OG000114
OG001112
OG002110
OG003116
OG004112
Title
Denominators
Categories
Title
Measurements
OG0004.000± 0.941
OG0014.080± 0.773
OG0024.209± 0.679
OG0034.224± 0.781
OG0044.080± 0.829
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
ANCOVA included MMSE stratification (>=20, <20) at baseline (BL) and treatment, CIBIS is included as BL adjustment term.
0.343
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
-0.10
Standard Error of the Mean
0.11
2-Sided
95
-0.32
0.11
Other
OG001
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
ANCOVA included MMSE stratification (>=20, <20) at baseline (BL) and treatment, CIBIS is included as BL adjustment term.
0.645
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
-0.05
Standard Error of the Mean
0.11
2-Sided
95
-0.26
0.16
Other
OG002
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
ANCOVA included MMSE stratification (>=20, <20) at baseline (BL) and treatment, CIBIS is included as BL adjustment term.
0.448
p-values are nominal without multiplicity adjustment.
Mean Difference (Final Values)
0.08
Standard Error of the Mean
0.11
2-Sided
95
-0.13
0.30
Other
OG003
OG004
Analysis of Covariance (ANCOVA)
ANCOVA
ANCOVA included MMSE stratification (>=20, <20) at baseline (BL) and treatment, CIBIS is included as BL adjustment term.
0.340
p-values are nominal without multiplicity adjustment.