Alzheimer DiseasePhase 2NCT02337907
BI 409306 in Patients With Cognitive Impairment Due to Alzheimer's Disease.
A Phase 2 study testing BI 409306 and Donepezil in people with Alzheimer Disease, run by Boehringer Ingelheim at 60 sites in 11 countries.
Trial summary
The study is designed to compare the effects of BI 409306 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- BI 409306 and Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 329 participants
- Where
- 60 sitesin 11 countries
- Study dates
- 21 Jan 2015to 10 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
60 sites in 11 countries.
60 sites in 11 countries
United States10 sites
The Memory Clinic
Bennington, Vermont, 05201
ANI Neurology, PLLC, dba Alzheimer's Memory Center
Charlotte, North Carolina, 28270
Memory Enhancement Center of America, Inc.
Eatontown, New Jersey, 07724
Indiana University
Indianapolis, Indiana, 46202
Bioclinica Research
Orlando, Florida, 32806
Psychiatry And Alzheimer's Care of Rochester, PLLC
Rochester, New York, 14623
California Neuroscience Research
Sherman Oaks, California, 91403
Richmond Behavioral Associates
Staten Island, New York, 10312
Tulsa Clinical Research, LLC
Tulsa, Oklahoma, 74104
Premiere Research Institute
West Palm Beach, Florida, 33407
Germany9 sites
Praxis Dr. med. Volker Schumann
Berlin, 10245
emovis GmbH
Berlin, 10629
St. Josef- und St. Elisabeth-Hospital gGmbH
Bochum, 44791
Neuro Centrum Science GmbH
Erbach im Odenwald, 64711
AFL Arzneimittelforschung Leipzig GmbH
Leipzig, 04107
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Zentralinstitut für seelische Gesundheit
Mannheim, 68159
Universitätsklinikum Ulm
Ulm, 89081
Neurologie und Psychiatrie / Psychotherapie
Westerstede, 26655
Poland8 sites
Podlassian Center of Psychogeriatry, Bialystok
Bialystok, 15-756
Mental Health Center Biomed
Kielce, 25-411
Non-Public Outpatient Clinic Neuromed M. i M. Nastaj
Lublin, 20-064
Inst. of Rural Health, Spec. Outp. Clin. & Rural Occup. Dis.
Lublin, 20-090
Non-Public Outpatient Clinic Neuro-Kard Ilkowski & Partners
Poznan, 61-853
Medical Center Senior
Sopot, 81-855
EUROMEDIS Sp. z o.o., Szczecin
Szczecin, 70-111
Reg. Specialist Hospital Wroclaw, Research & Develop. Center
Wroclaw, 51-124
Portugal8 sites
Hospital Fernando Fonseca, EPE
Amadora, 2700-276
Hospital de Braga-Escala Braga
Braga, 4710-243
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
Coimbra, 3000-075
Hospital Senhora Oliveira Guimarães,EPE
Guimarães, 4835-044
CHLO, EPE - Hospital Egas Moniz
Lisbon, 1349-019
Hospital Beatriz Ângelo
Loures, 2674-514
ULSM, EPE - Hospital Pedro Hispano
Matosinhos Municipality, 4454-509
Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
Santa Maria da Feira, 4520-211
France7 sites
HOP Pellegrin
Bordeaux, 33076
HOP Bocage
Dijon, 21079
HOP Timone
Marseille, 13385
HOP Gui de Chauliac
Montpellier, 34295
HOP Nord Laënnec
Nantes, 44093
HOP La Pitié Salpêtrière
Paris, 75651
HOP Jean Bernard, Géria, Poitiers
Poitiers, 86021
Belgium4 sites
Brussels-UNIV Brugmann -Horta
Brussels, 1020
AZ Sint-Blasius
Dendermonde, 9200
UNIV UZ Gent
Ghent, 9000
Mons - UNIV Ambroise Paré
Mons, 7000
Canada4 sites
University of Calgary
Calgary, Alberta, T2N 4Z6
Dr. Alexander McIntyre Inc.
Penticton, British Columbia, V2A 4M4
Institut universitaire de geriatrie Sherbrooke
Québec, J1J 3H5
Pasqua Hospital
Regina, Saskatchewan, S4T 1A5
United Kingdom4 sites
Royal United Hospital
Bath, BA1 3NG
Ninewells Hospital & Medical School
Dundee, Scotland, DD19SY
West Devon (Tavistock) CMHT & Memory Clinic (EDI)
Ivybridge, PL219AB
Re-Cognition Health
Plymouth, PL6 8BT
Italy3 sites
P.O. Bellaria IRCCS Istituto delle scienze Neurologiche di Bologna
Bologna, 40139
Azienda Ospedaliera Careggi
Florence, 50134
Azienda Ospedaliera di Parma
Parma, 43126
Netherlands2 sites
Jeroen Bosch Ziekenhuis-Hertogenbosch
's-Hertogenbosch, 5223 GZ
Brain Research Center
Amsterdam, 1081 GN
About this study
Official title: 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
The study is designed to compare the effects of BI 409306 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease
- Conditions
- Alzheimer Disease
- Being tested
- Placebo, BI 409306, Donepezil
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
for blinding purposes
PlaceboDrug
BI 409306Drug
DonepezilDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo comparator | Placebo comparator | Not described Receives: Drug: Placebo |
| BI 409306 dose 1 | Experimental | Not described Receives: Drug: Placebo; Drug: BI 409306 |
| BI 409306 dose 2 | Experimental | Not described Receives: Drug: Placebo; Drug: BI 409306 |
| BI 409306 dose 3 | Experimental | Not described Receives: Drug: Placebo; Drug: BI 409306 |
| Active Comparator Donepezil | Active comparator | Not described Receives: Drug: Placebo; Drug: Donepezil |
| BI 409306 dose 4 | Experimental | Not described Receives: Drug: Placebo; Drug: BI 409306 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.
Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Least Squares Mean is actually an adjusted mean change from baseline.
Measured: Baseline and 12 weeks
Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Sister Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)
Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. The number of low test scores decreased with higher levels of intellectual abilities. Least Squares Mean is actually an adjusted mean change from baseline.
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Change From Baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Total Score After 12-week Treatment
Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) is a rating scale used to assess basic and instrumental activities of daily living. In the full version of the scale, 23 items are rated by the investigator using information supplied by the caregiver. Each item has a score range varying from 0-3 to 0-5. The sum score can range from 0 to 78. Higher scores indicate better function. Least Squares Mean is actually an adjusted mean change from baseline.
Measured: Baseline and 12 weeks
Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Total Score After 12-week Treatment
The CDR-SB is obtained through semi-structured interviews of patients and informants, and cognitive functioning was rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Each domain was rated on a 5-point scale of functioning as follows: 0-no impairment; 0.5-questionable impairment; 1-mild impairment; 2-moderate impairment and 3-severe impairment. Only personal care was scored on a 4-point scale without a 0.5 rating available. The higher the score, the greater the severity of dementia. Least Squares Mean is actually an adjusted mean change from baseline.
Measured: Baseline and 12 weeks
Change From Baseline in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog11) Total Score After 12-week Treatment
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog11) is an 11-item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 to 70. The greater the dysfunction, the greater the score. Least Squares Mean is actually an adjusted mean change from baseline.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2015 (estimated)
- Study start21 Jan 2015
- Primary completion15 Sep 2017
- Study completion10 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 329 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337907
- Sponsor's protocol ID
- 1289.7
- Other IDs
- 2013-005040-28
- Status last verified
- Oct 2018
- First submitted
- 23 Dec 2014
- Last updated
- 14 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 30755255
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02337907
- Acronym / sponsor ID
- 1289.7
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 329 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 21 Jan 2015 (actual)
- Primary completion
- 15 Sep 2017 (actual)
- Study completion
- 10 Oct 2017 (actual)
- First posted
- 14 Jan 2015 (estimated)
- Results
- Posted 14 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is designed to compare the effects of BI 409306 compared to placebo in patients with cognitive impairment due to Alzheimer's Disease
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo comparator | Placebo comparator | Drug: Placebo |
| BI 409306 dose 1 | Experimental | Drug: Placebo, Drug: BI 409306 |
| BI 409306 dose 2 | Experimental | Drug: Placebo, Drug: BI 409306 |
| BI 409306 dose 3 | Experimental | Drug: Placebo, Drug: BI 409306 |
| Active Comparator Donepezil | Active comparator | Drug: Placebo, Drug: Donepezil |
| BI 409306 dose 4 | Experimental | Drug: Placebo, Drug: BI 409306 |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebofor blinding purposes | Drug | Active Comparator Donepezil, BI 409306 dose 1, BI 409306 dose 2, BI 409306 dose 3, BI 409306 dose 4, Placebo comparator |
| Placebo | Drug | Placebo comparator |
| BI 409306 | Drug | BI 409306 dose 1, BI 409306 dose 2, BI 409306 dose 3, BI 409306 dose 4 |
| Donepezil | Drug | Active Comparator Donepezil |
Primary outcome
Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment.
Time frame: Baseline and 12 weeks
Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Least Squares Mean is actually an adjusted mean change from baseline.
Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment From Two Sister Trials, Present 1289.5 (NCT02240693) and 1289.7 (NCT02337907)
Time frame: Baseline and 12 weeks
Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB consists of 9 validated components. Raw scores on each of the 9 NTB tests were converted to z-scores using the baseline means and standard deviations (SDs) for each test. The resultant z-scores were averaged to obtain a total z-score, incorporating all 9 NTB tests. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. The number of low test scores decreased with higher levels of intellectual abilities. Least Squares Mean is actually an adjusted mean change from baseline.
3 secondary outcomes
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30755255Frolich 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.
- Related InfoLink provided by the sponsor.
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
60 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BI 409306 and Donepezil in people with Alzheimer Disease, run by Boehringer Ingelheim at 60 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in United States, Germany, Poland, Portugal, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Neuropsychological Test Battery in Total Z-score After 12-week Treatment. (time frame: Baseline and 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02337907, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018; AzTrials last refreshed its copy on 8 Nov 2026.