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

NCT02337907 | Completed Phase 2 Results

• 2 other identifiers: 1289.72013-005040-28
• Study Type: interventional
• Target: 329
• Locations: 11 countries
• Sites: 60

Brief 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

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  Baseline and 12 weeks

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

  Baseline and 12 weeks

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

  Baseline and 12 weeks

Study Arms (6)

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

Interventions

Placebo DRUG

for blinding purposes

Active Comparator Donepezil; BI 409306 dose 1; BI 409306 dose 2; BI 409306 dose 3; BI 409306 dose 4; 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

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (60)

California Neuroscience Research

Sherman Oaks, California, 91403, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

Psychiatry And Alzheimer's Care of Rochester, PLLC

Rochester, New York, 14623, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

ANI Neurology, PLLC, dba Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Tulsa Clinical Research, LLC

Tulsa, Oklahoma, 74104, United States

Location

The Memory Clinic

Bennington, Vermont, 05201, United States

Location

Private Practice for Psychiatry and Neurology

Vienna, 1130, Austria

Location

Brussels-UNIV Brugmann -Horta

Brussels, 1020, Belgium

Location

AZ Sint-Blasius

Dendermonde, 9200, Belgium

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

Mons - UNIV Ambroise Paré

Mons, 7000, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Dr. Alexander McIntyre Inc.

Penticton, British Columbia, V2A 4M4, Canada

Location

Pasqua Hospital

Regina, Saskatchewan, S4T 1A5, Canada

Location

Institut universitaire de geriatrie Sherbrooke

Québec, J1J 3H5, Canada

Location

HOP Pellegrin

Bordeaux, 33076, France

Location

HOP Bocage

Dijon, 21079, France

Location

HOP Timone

Marseille, 13385, France

Location

HOP Gui de Chauliac

Montpellier, 34295, France

Location

HOP Nord Laënnec

Nantes, 44093, France

Location

HOP La Pitié Salpêtrière

Paris, 75651, France

Location

HOP Jean Bernard, Géria, Poitiers

Poitiers, 86021, France

Location

Praxis Dr. med. Volker Schumann

Berlin, 10245, Germany

Location

emovis GmbH

Berlin, 10629, Germany

Location

St. Josef- und St. Elisabeth-Hospital gGmbH

Bochum, 44791, Germany

Location

Neuro Centrum Science GmbH

Erbach im Odenwald, 64711, Germany

Location

AFL Arzneimittelforschung Leipzig GmbH

Leipzig, 04107, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Zentralinstitut für seelische Gesundheit

Mannheim, 68159, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Neurologie und Psychiatrie / Psychotherapie

Westerstede, 26655, Germany

Location

P.O. Bellaria IRCCS Istituto delle scienze Neurologiche di Bologna

Bologna, 40139, Italy

Location

Azienda Ospedaliera Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliera di Parma

Parma, 43126, Italy

Location

Jeroen Bosch Ziekenhuis-Hertogenbosch

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Brain Research Center

Amsterdam, 1081 GN, Netherlands

Location

Podlassian Center of Psychogeriatry, Bialystok

Bialystok, 15-756, Poland

Location

Mental Health Center Biomed

Kielce, 25-411, Poland

Location

Non-Public Outpatient Clinic Neuromed M. i M. Nastaj

Lublin, 20-064, Poland

Location

Inst. of Rural Health, Spec. Outp. Clin. & Rural Occup. Dis.

Lublin, 20-090, Poland

Location

Non-Public Outpatient Clinic Neuro-Kard Ilkowski & Partners

Poznan, 61-853, Poland

Location

Medical Center Senior

Sopot, 81-855, Poland

Location

EUROMEDIS Sp. z o.o., Szczecin

Szczecin, 70-111, Poland

Location

Reg. Specialist Hospital Wroclaw, Research & Develop. Center

Wroclaw, 51-124, Poland

Location

Hospital Fernando Fonseca, EPE

Amadora, 2700-276, Portugal

Location

Hospital de Braga-Escala Braga

Braga, 4710-243, Portugal

Location

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, 3000-075, Portugal

Location

Hospital Senhora Oliveira Guimarães,EPE

Guimarães, 4835-044, Portugal

Location

CHLO, EPE - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

Hospital Beatriz Ângelo

Loures, 2674-514, Portugal

Location

ULSM, EPE - Hospital Pedro Hispano

Matosinhos Municipality, 4454-509, Portugal

Location

Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião

Santa Maria da Feira, 4520-211, Portugal

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

Ninewells Hospital & Medical School

Dundee, Scotland, DD19SY, United Kingdom

Location

West Devon (Tavistock) CMHT & Memory Clinic (EDI)

Ivybridge, PL219AB, United Kingdom

Location

Re-Cognition Health

Plymouth, PL6 8BT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30755255 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

BI 409306; Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

There were 5 patients who were randomised to donepezil arm which was dropped from the trial with protocol amendment. No further patients were randomised to this arm, but patients already randomised continued in the trial as originally planned.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: January 14, 2015
• Study Start: January 21, 2015
• Primary Completion: September 15, 2017
• Study Completion: October 10, 2017
• Last Updated: November 14, 2018
• Results First Posted: November 14, 2018

Record last verified: 2018-10

Locations

PT (8); PL (8); IT (3); AU (1); BE (4); US (10); NL (2); DE (9); GB (4); FR (7); CA (4)