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

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 Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: Donepezil; Drug: BI 409306; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 329
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1130
    • Private Practice for Psychiatry and Neurology
• Belgium
  • Brussel, Belgium, 1020
    • Brussels-UNIV Brugmann -Horta
  • Dendermonde, Belgium, 9200
    • AZ Sint-Blasius
  • Gent, Belgium, 9000
    • UNIV UZ Gent
  • Mons, Belgium, 7000
    • Mons - UNIV Ambroise Paré
• Canada
  • Quebec, Canada, J1J 3H5
    • Institut universitaire de geriatrie Sherbrooke
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 4M4
      • Dr. Alexander McIntyre Inc.
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 1A5
      • Pasqua Hospital
• France
  • Bordeaux, France, 33076
    • HOP Pellegrin
  • Dijon, France, 21079
    • HOP Bocage
  • Marseille, France, 13385
    • HOP Timone
  • Montpellier, France, 34295
    • HOP Gui de Chauliac
  • Nantes, France, 44093
    • HOP Nord Laennec
  • Paris, France, 75651
    • HOP La Pitié Salpêtrière
  • Poitiers, France, 86021
    • HOP Jean Bernard, Géria, Poitiers
• Germany
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10245
    • Praxis Dr. med. Volker Schumann
  • Bochum, Germany, 44791
    • St. Josef- und St. Elisabeth-Hospital gGmbH
  • Erbach, Germany, 64711
    • Neuro Centrum Science GmbH
  • Leipzig, Germany, 04107
    • AFL Arzneimittelforschung Leipzig GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Mannheim, Germany, 68159
    • Zentralinstitut für seelische Gesundheit
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • Westerstede, Germany, 26655
    • Neurologie und Psychiatrie / Psychotherapie
• Italy
  • Bologna, Italy, 40139
    • P.O. Bellaria IRCCS Istituto delle scienze Neurologiche di Bologna
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Careggi
  • Parma, Italy, 43126
    • Azienda Ospedaliera Di Parma
• Netherlands
  • 's-HERTOGENBOSCH, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis-Hertogenbosch
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center
• Poland
  • Bialystok, Poland, 15-756
    • Podlassian Center of Psychogeriatry, Bialystok
  • Kielce, Poland, 25-411
    • Mental Health Center Biomed
  • Lublin, Poland, 20-064
    • Non-Public Outpatient Clinic Neuromed M. i M. Nastaj
  • Lublin, Poland, 20-090
    • Inst. of Rural Health, Spec. Outp. Clin. & Rural Occup. Dis.
  • Poznan, Poland, 61-853
    • Non-Public Outpatient Clinic Neuro-Kard Ilkowski & Partners
  • Sopot, Poland, 81-855
    • Medical Center Senior
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z o.o., Szczecin
  • Wroclaw, Poland, 51-124
    • Reg. Specialist Hospital Wroclaw, Research & Develop. Center
• Portugal
  • Amadora, Portugal, 2700-276
    • Hospital Fernando Fonseca, EPE
  • Braga, Portugal, 4710-243
    • Hospital de Braga-Escala Braga
  • Coimbra, Portugal, 3000-075
    • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Guimarães, Portugal, 4835-044
    • Hospital Senhora Oliveira Guimarães,EPE
  • Lisboa, Portugal, 1349-019
    • CHLO, EPE - Hospital Egas Moniz
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Angelo
  • Matosinhos, Portugal, 4454-509
    • ULSM, EPE - Hospital Pedro Hispano
  • Santa Maria da Feira, Portugal, 4520-211
    • Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital
  • Dundee, Scotland, United Kingdom, DD19SY
    • Ninewells Hospital & Medical School
  • Ivybridge, United Kingdom, PL219AB
    • West Devon (Tavistock) CMHT & Memory Clinic (EDI)
  • Plymouth, United Kingdom, PL6 8BT
    • Re-Cognition Health
• United States
  • California
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research
  • Florida
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
  • New York
    • Rochester, New York, United States, 14623
      • Psychiatry and Alzheimer's Care of Rochester, PLLC
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • ANI Neurology, PLLC, dba Alzheimer's Memory Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research, LLC
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo comparator	Drug: Placebo; Drug: Placebo; for blinding purposes
Experimental: BI 409306 dose 1	Drug: Placebo; Drug: BI 409306; Drug: Placebo; for blinding purposes
Experimental: BI 409306 dose 2	Drug: Placebo; Drug: BI 409306; Drug: Placebo; for blinding purposes
Experimental: BI 409306 dose 3	Drug: Placebo; Drug: BI 409306; Drug: Placebo; for blinding purposes
Experimental: BI 409306 dose 4	Drug: Placebo; Drug: BI 409306; Drug: Placebo; for blinding purposes
Active Comparator: Active Comparator Donepezil	Drug: Placebo; Drug: Donepezil; Drug: Placebo; for blinding purposes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 12 weeks
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.	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.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2015
• Primary Completion (Actual): September 15, 2017
• Study Completion (Actual): October 10, 2017

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: January 9, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 18, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil; BI 409306
• Other Study ID Numbers: 1289.7; 2013-005040-28 (EudraCT Number)