CompletedPhase 2Results posted

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

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

Lead sponsor

Boehringer Ingelheim

Assets

BI 409306 / Donepezil

Listed sites

Recruiting sites

Enrollment

329

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Study partner/caregiver required•AD symptomatic therapy: stable ≥3 months

Primary endpoint

•Neuropsychological Test Battery in Total Z-score After 12-week Treatment

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID1289.7

Eudract number2013-005040-28

NCT IDNCT02337907

Timeline

Milestones

Study first posted2015-01-14estimated

Study start2015-01-21actual

Primary completion2017-09-15actual

Study completion2017-10-10actual

Last update posted2018-11-14actual

Results first posted2018-11-14actual

Assets

Drug assets

BI 409306 Donepezil

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (10)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Memory

Function / daily living

Global cognition

6 endpoints

Primary/protocol endpoint

Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.

Time frame:Baseline and 12 weeks

change from baseline, improvement

Primary/protocol endpoint

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)

Time frame:Baseline and 12 weeks

change from baseline, improvement

Primary/registry result

Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.

Time frame:Baseline and 12 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Z-score	Standard error
BI 409306 10 Milligram (mg) Once Daily (QD)n=54 Participants	0.13	0.059
BI 409306 25 mg QDn=50 Participants	0.17	0.061
BI 409306 50 mg QDn=55 Participants	0.16	0.056
BI 409306 25 mg Twice Daily (BID)n=55 Participants	0.01	0.060
Pooled BI 409306n=214 Participants	0.12	0.30
Placebo Matching BI 409306n=101 Participants	0.15	0.045

Mean Difference (Final Values)-0.0295% CI-0.163 - 0.124p0.7907Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.0295% CI-0.125 - 0.171p0.7622Mixed Model Repeated Measurement (MMRM)

Mean Difference (Net)0.0195% CI-0.130 - 0.152p0.8789Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.1495% CI-0.285 - 0.006p0.0609Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.0395% CI-0.135 - 0.074p0.5687Mixed Model Repeated Measurement (MMRM)

Primary/registry result

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)

Time frame:Baseline and 12 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Z-score	Standard error
BI 409306 10 Milligram (mg) Once Daily (QD)n=76 Participants	0.20	0.046
BI 409306 25 mg QDn=71 Participants	0.19	0.048
BI 409306 50 mg QDn=76 Participants	0.19	0.046
BI 409306 25 mg Twice Daily (BID)n=76 Participants	0.10	0.047
Pooled BI 409306n=299 Participants	0.17	0.025
Placebo Matching BI 409306n=144 Participants	0.19	0.035

Mean Difference (Final Values)0.0195% CI-0.101 - 0.120p0.8694Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.0095% CI-0.116 - 0.109p0.9512Mixed Model Repeated Measurement (MMRM)

Mean Difference (Net)0.0095% CI-0.105 - 0.115p0.9321Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.0995% CI-0.199 - 0.025p0.1288Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.0295% CI-0.098 - 0.061p0.6492Mixed Model Repeated Measurement (MMRM)

Secondary/protocol endpoint

Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Unit on scale	Standard error
BI 409306 10 Milligram (mg) Once Daily (QD)n=54 Participants	0.1	0.23
BI 409306 25 mg QDn=50 Participants	0.3	0.23
BI 409306 50 mg QDn=55 Participants	0.1	0.21
BI 409306 25 mg Twice Daily (BID)n=55 Participants	0.2	0.22
Placebo Matching BI 409306n=101 Participants	0.1	0.16

Mean Difference (Final Values)0.195% CI-0.46 - 0.64p0.7551Mixed-effects Model for Repeated Measure

Mean Difference (Final Values)0.395% CI-0.29 - 0.80p0.3643Mixed-effects Model for Repeated Measure

Mean Difference (Final Values)0.195% CI-0.45 - 0.60p0.7822Mixed-effects Model for Repeated Measure

Mean Difference (Final Values)0.195% CI-0.43 - 0.65p0.6889Mixed-effects Model for Repeated Measure

Memory

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Unit on scale	Standard error
BI 409306 10 Milligram (mg) Once Daily (QD)n=54 Participants	1.14	0.738
BI 409306 25 mg QDn=50 Participants	0.94	0.776
BI 409306 50 mg QDn=55 Participants	1.11	0.746
BI 409306 25 mg Twice Daily (BID)n=55 Participants	2.29	0.746
Placebo Matching BI 409306n=101 Participants	-0.18	0.568

Mean Difference (Final Values)1.3295% CI-0.52 - 3.15p0.1595ANCOVA

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.

Mean Difference (Final Values)1.1295% CI-0.77 - 3.01p0.2455ANCOVA

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.

Mean Difference (Final Values)1.2895% CI-0.57 - 3.13p0.1732ANCOVA

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.

Mean Difference (Final Values)2.4795% CI0.63 - 4.31p0.0088ANCOVA

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.

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment

Time frame:Baseline and 12 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Unit on scale	Standard error
BI 409306 10 Milligram (mg) Once Daily (QD)n=54 Participants	0.10	0.853
BI 409306 25 mg QDn=50 Participants	-0.99	0.892
BI 409306 50 mg QDn=55 Participants	0.35	0.847
BI 409306 25 mg Twice Daily (BID)n=55 Participants	-1.07	0.855
Placebo Matching BI 409306n=101 Participants	-0.58	0.639

Mean Difference (Final Values)0.6795% CI-1.43 - 2.77p0.5287ANCOVA

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.

Mean Difference (Final Values)-0.4195% CI-2.57 - 1.76p0.7105ANCOVA

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.

Mean Difference (Final Values)0.9395% CI-1.16 - 3.03p0.3822ANCOVA

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.

Mean Difference (Final Values)-0.4995% CI-2.59 - 1.61p0.6472ANCOVA

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.

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Frolich L, Wunderlich G, Thamer C, Roehrle M, Garcia M Jr, Dubois B. Evaluation of the efficacy, safety and tolerability of orally administered BI 409306, a novel phosphodiesterase type 9 inhibitor, in two randomised controlled phase II studies in patients with prodromal and mild Alzheimer's disease. Alzheimers Res Ther. 2019 Feb 12;11(1):18. doi: 10.1186/s13195-019-0467-2.
PMID30755255via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.