CompletedPhase 2Results posted

Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo

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 Disease

Lead sponsor

Boehringer Ingelheim

Asset

BI 409306

Listed sites

Recruiting sites

Enrollment

128

actual

Study population

Alzheimer’s disease

Key I/E criteria

•prodromal AD•CDR global 0•Study partner/caregiver required

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 ID1289.5

Eudract number2013-005031-24

NCT IDNCT02240693

Timeline

Milestones

Study first posted2014-09-16estimated

Study start2015-01-15actual

Primary completion2017-09-18actual

Study completion2017-10-09actual

Last update posted2018-11-28actual

Results first posted2018-11-28actual

Assets

Drug assets

BI 409306

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male and female patients with an age of at least 55 years

•Body weight not lower than 50 kgs

•Patients with a confirmed diagnosis of prodromal Alzheimer's Dementia (AD) on neuropsychological testing defined as:

Mini-Mental State Examination (MMSE) score: greater or equal 24 and a global Clinical Dementia Rating (CDR)-score of 0 or 0.5 and

Free and Cued Selective Recall Reminding Test (FCSRT) score:

free recall test: lower or equal 20 (out of 48) and total recall test: lower or equal 42 (out of 48)

Patients who do not reach the required score in FCSRT will additionally perform the Wechsler Memory Visual Paired Associates test. If the Wechsler Memory Visual Paired Associates test shows a cognitive deficit worse than 1 standard deviation to the mean (compared to the reference values of age and educational norms for inclusion), then the patients can be considered to be eligible for the study.

•Confirmation of abnormal markers of AD pathology either via a), or alternatively b) mentioned below:

1. Presence in cerebrospinal fluid of (samples taken within past 4 months may be eligible,:

low Aß1-42 concentrations (< 640 pg/mL) and increased total tau concentrations (> 375 pg/ml), or / and low Aß1-42 concentrations (< 640 pg/mL) and increased phospho-tau concentrations (> 52 pg/mL in cerebrospinal fluid), or

2. Abnormal amyloid deposition in a cerebral Positron Emission Tomography (PET) scan. Scans performed in the past according to the recommendation in the protocol are acceptable

•Patients who have not received prescribed drugs for treatment of AD (including acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine) and Memantine within three 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 given written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to any study procedures. All patients must be able to give informed consent personally and have capacity for such consent. An informed consent given by a legal representative will not be accepted.

•Patients must have a reliable study partner (per investigator judgement, for instance a family member, partner, guardian etc.)

Exclusion criteria

•Mild cognitive impairment with any etiology other than prodromal AD (for example: neurosyphilis, craniocerebral trauma, small vessel disease) based on clinical data and/or current laboratory findings and/or a pre-existing MRI or CT of the brain (CCT). If previous cranial imaging is not available or older than 12 months prior to screening then a CCT or MRI needs to be performed at screening

•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 of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years

•Medical history or diagnosis of any of symptomatic and unstable/uncontrolled conditions per investigator judgement

•Severe renal impairment defined with a glomerular filtration rate (GFR) < 30ml/min/1.73m2 in the screening central lab report

•Any other psychiatric disorders such as schizophrenia, or mental retardation

•Any suicidal actions in the past 2 years (per investigator judgement i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)

•Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)

•Previous participation in investigational drug studies of mild cognitive impairment within three months prior to screening. Having received active treatment in any other study targeting disease modification like Aß immunization and tau therapies. Previous participation in studies with non-prescription medications, vitamins or other nutritional formulations is allowed.

•Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic and Statistical Manual of Mental Disorders [DSM-V] or in the opinion of the investigator) within the last two years, or a positive urine drug screen for cocaine, heroin, or marijuana.

•Known history of HIV infection

•Any planned surgeries requiring general anaesthesia, or hospitalisation for more than 1 day during the study period

•Pre-menopausal women (last menstruation <= 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control

•For male patients: Men who are able to father a child, unwilling to be abstinent or to use an adequate form of effective contraception for the duration of study participation and for at least 28 days after treatment has ended.

•Use of any investigational drug or procedure for other indications within 3 months or 6 half-lives (whichever is longer) prior to randomization.

•Intake of the following medications within 3 months prior to randomization and intended to be initiated during the duration of the trial:

1. tricyclic antidepressants,

2. antidepressants that are monoamine oxidase inhibitors,

3. neuroleptics with moderate or greater anticholinergic potency (e.g. chlorpromazine, fluphenazine, loxapine, perphenazine, thioridazine),

4. anticholinergic medications

The following drugs may be given as needed if the total daily dose was stable 8 weeks prior to randomisation and is expected to be for the duration of the trial:

1. neuroleptics listed in the protocol

2. benzodiazepines and sedatives listed in the protocol

-Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed.

-Known hypersensitivity to the drug product excipients

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 Twin 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=20 Participants	0.35	0.061
BI 409306 25 mg QDn=19 Participants	0.20	0.063
BI 409306 50 mg QDn=16 Participants	0.26	0.065
BI 409306 25 mg Twice Daily (BID)n=18 Participants	0.32	0.064
Pooled BI 409306n=73 Participants	0.29	0.031
Placebo Matching BI 409306n=39 Participants	0.27	0.043

Mean Difference (Final Values)0.0795% CI-0.074 - 0.223p0.3236Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.0795% CI-0.220 - 0.082p0.3694Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.0295% CI-0.171 - 0.139p0.8374Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.0595% CI-0.106 - 0.199p0.5484Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.0195% CI-0.092 - 0.121p0.7905Mixed Model Repeated Measurement (MMRM)

Primary/registry result

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)

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=67 Participants	0.20	0.046
BI 409306 25 mg QDn=63 Participants	0.19	0.048
BI 409306 50 mg QDn=67 Participants	0.19	0.046
BI 409306 25 mg Twice Daily (BID)n=63 Participants	0.10	0.047
Pooled BI 409306n=260 Participants	0.17	0.025
Placebo Matching BI 409306n=122 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 (Final Values)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=21 Participants	0.0	0.19
BI 409306 25 mg QDn=19 Participants	0.4	0.20
BI 409306 50 mg QDn=16 Participants	-0.1	0.22
BI 409306 25 mg Twice Daily (BID)n=18 Participants	0.1	0.21
Placebo Matching BI 409306n=40 Participants	0.1	0.14

Mean Difference (Final Values)0.095% CI-0.49 - 0.46p0.9491Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.395% CI-0.15 - 0.84p0.1699Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)-0.295% CI-0.69 - 0.33p0.4948Mixed Model Repeated Measurement (MMRM)

Mean Difference (Final Values)0.195% CI-0.42 - 0.58p0.7548Mixed Model Repeated Measurement (MMRM)

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=19 Participants	0.98	0.885
BI 409306 25 mg QDn=17 Participants	0.62	0.935
BI 409306 50 mg QDn=19 Participants	0.12	0.875
BI 409306 25 mg Twice Daily (BID)n=19 Participants	-1.27	0.875
Placebo Matching BI 409306n=38 Participants	1.24	0.619

Mean Difference (Final Values)-0.2695% CI-2.40 - 1.89p0.8137ANCOVA

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)-0.6295% CI-2.84 - 1.60p0.5801ANCOVA

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-3.25 - 1.00p0.2978ANCOVA

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)-2.5195% CI-4.64 - -0.39p0.0209ANCOVA

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 ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) 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 ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living for Patients With Mild Cognitive Impairment) 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=19 Participants	0.24	0.896
BI 409306 25 mg QDn=18 Participants	1.79	0.921
BI 409306 50 mg QDn=20 Participants	-0.10	0.875
BI 409306 25 mg Twice Daily (BID)n=17 Participants	0.80	0.947
Placebo Matching BI 409306n=37 Participants	0.38	0.642

Mean Difference (Final Values)-0.1495% CI-2.33 - 2.04p0.8973ANCOVA

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)1.4095% CI-0.82 - 3.63p0.2141ANCOVA

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-2.64 - 1.67p0.6553ANCOVA

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)0.4295% CI-1.85 - 2.69p0.7166ANCOVA

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.