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Alzheimer DiseasePhase 2NCT02240693

Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo

A Phase 2 study testing BI 409306 in people with Alzheimer Disease, run by Boehringer Ingelheim at 52 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The study is designed to compare the effects of 4 different doses of orally administered BI 409306 to placebo in patients with Alzheimers 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
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
128 participants
Where
52 sitesin 12 countries
Study dates
15 Jan 2015to 9 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

  • 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)
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  • 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:
  • 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
  • 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.)

Who cannot join

  • 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
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  • 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:
  • tricyclic antidepressants,
  • antidepressants that are monoamine oxidase inhibitors,
  • neuroleptics with moderate or greater anticholinergic potency (e.g. chlorpromazine, fluphenazine, loxapine, perphenazine, thioridazine),
  • 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:
  • neuroleptics listed in the protocol
  • 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

Trial locations and contacts

52 sites in 12 countries.

52 sites in 12 countries

Poland8 sites

  • Podlassian Center of Psychogeriatry, Bialystok

    Bialystok, 15-732

  • Non-Public Outpat. Clinic "Dom Sue Ryder", PALLMED Sp. z o.o

    Bydgoszcz, 85-796

  • Non-Public Outpatient Clinic "Synapsa" Pawel Polrola, Kielce

    Kielce, 25-103

  • Mental Health Center Biomed

    Kielce, 25-411

  • 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

Other trials in Poland

United States7 sites

  • ANI Neurology, PLLC, dba Alzheimer's Memory Center

    Charlotte, North Carolina, 28270

  • Memory Enhancement Center of America, Inc.

    Eatontown, New Jersey, 07724

  • Orange County Neuropsychiatric Research Center LLC

    Orange, California, 92868

  • 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

Other trials in United States

Canada6 sites

  • University of Calgary

    Calgary, Alberta, T2N 4Z6

  • True North Clinical Research Halifax, Inc.

    Halifax, Nova Scotia, B3S 1M7

  • True North Clinical Research Kentville, Inc.

    Kentville, Nova Scotia, B4B 4K9

  • Institut universitaire de geriatrie Sherbrooke

    Québec, J1J 3H5

  • Toronto Memory Program

    Toronto, Ontario, M3B 2S7

  • Royal Jubilee Hospital

    Victoria, British Columbia, V8R 1J8

Other trials in Canada

Germany6 sites

  • Praxis Dr. med. Volker Schumann

    Berlin, 10245

  • emovis GmbH

    Berlin, 10629

  • AFL Arzneimittelforschung Leipzig GmbH

    Leipzig, 04107

  • Zentralinstitut für seelische Gesundheit

    Mannheim, 68159

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Neurologie und Psychiatrie / Psychotherapie

    Westerstede, 26655

Other trials in Germany

Spain6 sites

  • Hospital Universitario Fundación Alcorcón

    Alcorcon (Madrid), 28922

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital Universitario Virgen de la Arrixaca

    El Palmar (murcia), 30120

  • Hospital Universitari General de Catalunya

    Sant Cugat del Vallès, 08190

  • Hospital Mútua Terrassa

    Terrasa (Barcelona), 08221

Other trials in Spain

France5 sites

  • HOP Pierre Wertheimer

    Bron, 69677

  • HOP Gui de Chauliac

    Montpellier, 34295

  • HOP Nord Laënnec

    Nantes, 44093

  • HOP La Pitié Salpêtrière

    Paris, 75651

  • HOP Jean Bernard, Géria, Poitiers

    Poitiers, 86021

Other trials in France

Portugal4 sites

  • Hospital Fernando Fonseca, EPE

    Amadora, 2700-276

  • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

    Coimbra, 3000-075

  • CHLO, EPE - Hospital Egas Moniz

    Lisbon, 1349-019

  • CHLN, EPE - Hospital de Santa Maria

    Lisbon, 1649-035

Other trials in Portugal

Italy3 sites

  • A.O. Spedali Civili di Brescia

    Brescia, 25123

  • Osp. S. Giovanni di Dio

    Florence, 50143

  • Policlinico Gemelli

    Roma, 00168

Other trials in Italy

United Kingdom3 sites

  • Royal United Hospital

    Bath, BA1 3NG

  • Derriford Hospital

    Plymouth, PL21 9AB

  • Re-Cognition Health

    Plymouth, PL6 8BT

Other trials in United Kingdom

Austria2 sites

  • Landeskrankenhaus Hall, Abt.f. Psychatrie & Psychotherapie A

    Hall in Tirol, 6060

  • Private Practice for Psychiatry and Neurology

    Vienna, 1130

Other trials in Austria

Belgium1 site

  • Brussels-UNIV Brugmann -Horta

    Brussels, 1020

Other trials in Belgium

Netherlands1 site

  • Brain Research Center

    Amsterdam, 1081 GN

Other trials in Netherlands

About this study

Official title: 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

The study is designed to compare the effects of 4 different doses of orally administered BI 409306 to placebo in patients with Alzheimers Disease

Being tested
BI 409306, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BI 409306Drug

  • PlaceboDrug

  • BI 409306Drug

  • PlaceboDrug

  • PlaceboDrug

  • BI 409306Drug

  • BI 409306Drug

  • PlaceboDrug

  • PlaceboDrug

Study groups in NCT02240693
Study groupRoleWhat they receive
BI 409306 dose 1ExperimentalNot described
Receives: Drug: BI 409306; Drug: Placebo
BI 409306 dose 2ExperimentalNot described
Receives: Drug: Placebo; Drug: BI 409306
BI 409306 dose 3ExperimentalNot described
Receives: Drug: BI 409306; Drug: Placebo
BI 409306 dose 4ExperimentalNot described
Receives: Drug: BI 409306; Drug: Placebo
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline

    Measured: Baseline and 12 weeks

  2. 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)

    Neuropsychological Test Battery (NTB) response, defined as change from baseline in total z-score after 12 weeks of treatment. The NTB Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean at baseline. Negative numbers indicate values lower than baseline and positive numbers indicate values higher than baseline. Change from baseline will be calculated as the post-baseline composite z-score minus the pre-treatment z-score, such that a positive change indicates an improvement from baseline

    Measured: Baseline and 12 weeks

Secondary outcomes (3)

  1. 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

    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

  2. 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

  3. 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.

  1. First posted16 Sep 2014 (estimated)
  2. Study start15 Jan 2015
  3. Primary completion18 Sep 2017
  4. Study completion9 Oct 2017

Resources

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
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02240693
Sponsor's protocol ID
1289.5
Other IDs
2013-005031-24
Status last verified
Oct 2018
First submitted
15 Sep 2014
Last updated
28 Nov 2018

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BI 409306 in people with Alzheimer Disease, run by Boehringer Ingelheim at 52 sites in 12 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 15 inclusion and 25 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 28 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 52 sites in Poland, United States, Canada, Germany, Spain and 7 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 28 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 NCT02240693, 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 28 Nov 2018.

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