Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo

NCT02240693 | Completed Phase 2 Results

• 2 other identifiers: 1289.52013-005031-24
• Study Type: interventional
• Target: 128
• Locations: 12 countries
• Sites: 52

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

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 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

  Baseline and 12 weeks

• 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

  Baseline and 12 weeks

Secondary Outcomes (3)

• 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

  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 (5)

BI 409306 dose 1

EXPERIMENTAL

Drug: BI 409306; Drug: Placebo

BI 409306 dose 2

EXPERIMENTAL

Drug: Placebo; Drug: BI 409306

BI 409306 dose 3

EXPERIMENTAL

Drug: BI 409306; Drug: Placebo

BI 409306 dose 4

EXPERIMENTAL

Drug: BI 409306; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 409306 DRUG

BI 409306 dose 1

Placebo DRUG

BI 409306 dose 2

Eligibility Criteria

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

You may qualify if:

• 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)
• 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.)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (52)

Orange County Neuropsychiatric Research Center LLC

Orange, California, 92868, United States

Location

California Neuroscience Research

Sherman Oaks, California, 91403, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, 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

Landeskrankenhaus Hall, Abt.f. Psychatrie & Psychotherapie A

Hall in Tirol, 6060, Austria

Location

Private Practice for Psychiatry and Neurology

Vienna, 1130, Austria

Location

Brussels-UNIV Brugmann -Horta

Brussels, 1020, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

Location

True North Clinical Research Halifax, Inc.

Halifax, Nova Scotia, B3S 1M7, Canada

Location

True North Clinical Research Kentville, Inc.

Kentville, Nova Scotia, B4B 4K9, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Institut universitaire de geriatrie Sherbrooke

Québec, J1J 3H5, Canada

Location

HOP Pierre Wertheimer

Bron, 69677, 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

AFL Arzneimittelforschung Leipzig GmbH

Leipzig, 04107, Germany

Location

Zentralinstitut für seelische Gesundheit

Mannheim, 68159, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Neurologie und Psychiatrie / Psychotherapie

Westerstede, 26655, Germany

Location

A.O. Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Osp. S. Giovanni di Dio

Florence, 50143, Italy

Location

Policlinico Gemelli

Roma, 00168, Italy

Location

Brain Research Center

Amsterdam, 1081 GN, Netherlands

Location

Podlassian Center of Psychogeriatry, Bialystok

Bialystok, 15-732, Poland

Location

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

Bydgoszcz, 85-796, Poland

Location

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

Kielce, 25-103, Poland

Location

Mental Health Center Biomed

Kielce, 25-411, 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

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, 3000-075, Portugal

Location

CHLO, EPE - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

CHLN, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital Universitario Fundación Alcorcón

Alcorcon (Madrid), 28922, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar (murcia), 30120, Spain

Location

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, 08190, Spain

Location

Hospital Mútua Terrassa

Terrasa (Barcelona), 08221, Spain

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

Derriford Hospital

Plymouth, PL21 9AB, 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

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• 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: September 15, 2014
• First Posted: September 16, 2014
• Study Start: January 15, 2015
• Primary Completion: September 18, 2017
• Study Completion: October 9, 2017
• Last Updated: November 28, 2018
• Results First Posted: November 28, 2018

Record last verified: 2018-10

Locations

PT (4); US (7); GB (3); FR (5); NL (1); CA (6); IT (3); BE (1); PL (8); ES (6); DE (6); AU (2)