Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo

NCT ID: NCT02240693

Last Updated: 2018-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-15
• Study Completion Date: 2017-10-09

Brief 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

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BI 409306 dose 1

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 409306 dose 2

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

BI 409306

Intervention Type: DRUG

BI 409306 dose 3

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 409306 dose 4

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 409306

Intervention Type: DRUG

BI 409306

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Orange County Neuropsychiatric Research Center LLC

Orange, California, United States

California Neuroscience Research

Sherman Oaks, California, United States

Premiere Research Institute

West Palm Beach, Florida, United States

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States

Richmond Behavioral Associates

Staten Island, New York, United States

ANI Neurology, PLLC, dba Alzheimer's Memory Center

Charlotte, North Carolina, United States

Tulsa Clinical Research, LLC

Tulsa, Oklahoma, United States

Landeskrankenhaus Hall, Abt.f. Psychatrie & Psychotherapie A

Hall in Tirol, , Austria

Private Practice for Psychiatry and Neurology

Vienna, , Austria

Brussels-UNIV Brugmann -Horta

Brussels, , Belgium

University of Calgary

Calgary, Alberta, Canada

Royal Jubilee Hospital

Victoria, British Columbia, Canada

True North Clinical Research Halifax, Inc.

Halifax, Nova Scotia, Canada

True North Clinical Research Kentville, Inc.

Kentville, Nova Scotia, Canada

Toronto Memory Program

Toronto, Ontario, Canada

Institut universitaire de geriatrie Sherbrooke

Québec, , Canada

HOP Pierre Wertheimer

Bron, , France

HOP Gui de Chauliac

Montpellier, , France

HOP Nord Laënnec

Nantes, , France

HOP La Pitié Salpêtrière

Paris, , France

HOP Jean Bernard, Géria, Poitiers

Poitiers, , France

Praxis Dr. med. Volker Schumann

Berlin, , Germany

emovis GmbH

Berlin, , Germany

AFL Arzneimittelforschung Leipzig GmbH

Leipzig, , Germany

Zentralinstitut für seelische Gesundheit

Mannheim, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Neurologie und Psychiatrie / Psychotherapie

Westerstede, , Germany

A.O. Spedali Civili di Brescia

Brescia, , Italy

Osp. S. Giovanni di Dio

Florence, , Italy

Policlinico Gemelli

Roma, , Italy

Brain Research Center

Amsterdam, , Netherlands

Podlassian Center of Psychogeriatry, Bialystok

Bialystok, , Poland

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

Bydgoszcz, , Poland

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

Kielce, , Poland

Mental Health Center Biomed

Kielce, , Poland

Non-Public Outpatient Clinic Neuro-Kard Ilkowski & Partners

Poznan, , Poland

Medical Center Senior

Sopot, , Poland

EUROMEDIS Sp. z o.o., Szczecin

Szczecin, , Poland

Reg. Specialist Hospital Wroclaw, Research & Develop. Center

Wroclaw, , Poland

Hospital Fernando Fonseca, EPE

Amadora, , Portugal

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, , Portugal

CHLO, EPE - Hospital Egas Moniz

Lisbon, , Portugal

CHLN, EPE - Hospital de Santa Maria

Lisbon, , Portugal

Hospital Universitario Fundación Alcorcón

Alcorcon (Madrid), , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Virgen de la Arrixaca

El Palmar (murcia), , Spain

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, , Spain

Hospital Mútua Terrassa

Terrasa (Barcelona), , Spain

Royal United Hospital

Bath, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Re-Cognition Health

Plymouth, , United Kingdom

Countries

United States; Austria; Belgium; Canada; France; Germany; Italy; Netherlands; Poland; Portugal; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30755255 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-005031-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1289.5

Identifier Type: -

Identifier Source: org_study_id