Clinical trial NCT01741194: AC-1204 26-Week Long Term Efficacy Response Trial With Optional Open-label Ext
Official title: A 26-Week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Daily Administration of AC-1204 in Participants With Mild to Moderate Alzheimer's Disease (AD) With an Optional 26-Week Open Label Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer's Disease
Lead sponsor: Cerecin
Sponsor class: INDUSTRY
First posted: 2012-12-04
Enrollment: 418
Sex: ALL
Minimum age (years): 66
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study will evaluate the effects of daily dosing of AC-1204 on cognition, activities of daily living, resource utilization, quality of life, pharmacokinetic measures and safety among participants with mild to moderate Alzheimer's Disease.


Eligibility criteria: Inclusion Criteria:

* Dementia status of mild to moderate
* CT or MRI scan within 18 months prior to screening compatible with a diagnosis of probable Alzheimer's disease
* Score on the Wechsler Memory Scale - Logical Memory II recall below a pre-determined cut-off, adjusted for education level
* Confirmed apolipoprotein E genotype prior to randomization
* Prior and current use of medication that corresponds with protocol requirements
* Stable medical condition, with the exception of dementia, for at least 3 consecutive months prior to screening
* No active suicidal thoughts within 6 months of screening, no active history of suicide attempt in the previous 2 years, no more than 1 lifetime suicide attempt, no serious suicidal risk
* Able to comply with protocol testing and procedures for the duration of the study
* Has a permanent caregiver (caregiver is not expected to change during the course of the study) who is willing to attend all visits, oversee the participant's compliance with protocol procedures and study medication administration, and report on the participant's status
* Resides in the community (includes assisted living facilities, but excludes long-term care nursing facilities)
* Both participant and caregiver have the ability to read and write in English or Spanish and have hearing, vision and physical abilities adequate to perform the assessments (corrective aids allowed)
* Participant and caregiver have provided full written informed consent prior to the performance of any protocol-specified procedure. If participant is unable to provide informed consent due to cognitive status, provision of informed consent by cognitively intact legally acceptable representative (where this is in accordance with local laws, regulations and ethics committee policy)
* Participant is able to ingest oral medication

Exclusion Criteria:

* Current use, or use within 3 months of baseline, of medium-chain triglyceride-containing products
* Use of any other investigational agent within 60 days prior to screening
* Known allergy or hypersensitivity to milk or soy products
* In the opinion of the investigator, presence or history of advanced, severe, progressive or unstable disease of any type that could interfere with protocol assessments or put the participant at particular risk
* Any medical or neurological condition other than Alzheimer's disease that could explain the patient's dementia
* History or clinical laboratory evidence of moderate congestive heart failure
* Clinically significant ECG abnormalities at screening
* History of new cardiovascular events within 6 months prior to baseline
* History of or current psychiatric illness
* Major depression as determined by Cornell Scale for Depression in Dementia
* Insulin-dependent diabetics
* Systolic blood pressure \> 165 mmHg or diastolic blood pressure \> 95 mmHg
* Drop of 20 mm Hg systolic blood pressure or greater upon standing upright from a seated position within 3 minutes at screening
* Clinically significant anemia at screening
* Clinically significant renal disease or insufficiency at screening
* Laboratory values for liver function tests \> 2.5 times the upper limit of normal at screening or history of severe liver disease
* Fasting triglycerides \> 2.5 times the upper limit of normal at screening
* Clinically significant B12 deficiency within 12 month prior to screening
* Inflammatory bowel disease or peptic ulcer disease.
* Participants with current or a history of (within the last 5 years) complicated reflux disease or severe GERD that is not well-controlled by medication.
* Irritable bowel syndrome, diverticular disease (e.g., diverticulosis or diverticulitis), or chronic gastritis (exclusionary if there has been a diagnosis or an acute event within 5 years prior to Screening.)
* Has donated ≥ 2 units of blood within the 2 months prior to screening
* History of alcohol or drug abuse within 6 months prior to screening, or positive urine drug test at screening
* Participant or caregiver is an immediate family member or employee of the clinical site, sponsor or sponsor's agents
* An alternative cause for dementia other than Alzheimer's disease as determined by a required CT or MRI scan within 18 months prior to screening
* History of neoplasm or malignancies within 5 years prior to screening, except for basal cell or squamous cell carcinoma of the skin
* Clinically significant hypothyroidism as determined thyroid function testing at screening
* Participant has scheduled or expected hospitalization and/or surgery during the course of the study

Primary outcomes:
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
timeFrame: 26 weeks
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
timeFrame: 8 and 17 weeks
measure: Clock Draw Interpretation Scale (CDIS)
timeFrame: 8 and 17 weeks
measure: Alzheimer's Disease Co-operative Study - Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 26 weeks
measure: Alzheimer's Disease Co-operative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 26 weeks
measure: Quality of Life - Alzheimer's Disease (QoL-AD)
timeFrame: 26 weeks
measure: Resource Utilization in Dementia (RUD-Lite)
timeFrame: 26 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: 26 weeks
Other outcomes:
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
timeFrame: 26 weeks
measure: Clock Draw Interpretation Scale (CDIS)
timeFrame: 26 weeks
measure: Alzheimer's Disease Co-operative Study - Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 26 weeks
measure: Alzheimer's Disease Co-operative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 26 weeks
measure: Quality of Life - Alzheimer's Disease (QoL- AD)
timeFrame: 26 weeks
measure: Resource Utilization in Dementia (RUD-Lite)
timeFrame: 26 weeks
measure: Mini Mental State Exam (MMSE)
timeFrame: 26 weeks
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
timeFrame: 52 weeks
measure: Alzheimer's Disease Co-operative Study - Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 52 weeks
measure: Alzheimer's Disease Co-operative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 52 weeks
measure: Quality of Life - Alzheimer's Disease (QoL - AD)
timeFrame: 52 weeks
measure: Resource Utilization in Dementia (RUD-Lite)
timeFrame: 52 weeks
measure: Clock Draw Interpretation Scale (CDIS)
timeFrame: 52 weeks
measure: Ketone body levels (BHB)
timeFrame: baseline, 8, 17 and 26 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: 52 weeks
measure: Mini Mental State Exam (MMSE)
timeFrame: 52 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Department of Neurology, Memory Disorders Division
state: Alabama
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Hot Springs
country: United States
facility: Principals Research Group
state: Arkansas
city: Little Rock
country: United States
facility: Clinical Trials, Inc.
state: Arkansas
city: Bellflower
country: United States
facility: CITrials, Inc.
state: California
city: Beverly Hills
country: United States
facility: Southern Research LLC
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Downey
country: United States
facility: Diligent Clinical Trials
state: California
city: La Jolla
country: United States
facility: UCSD Comprehensive Alzheimer's Program
state: California
city: Laguna Hills
country: United States
facility: Alliance Research Centers
state: California
city: Laguna Hills
country: United States
facility: Senior Clinical Trials, Inc.
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Long Beach
country: United States
facility: Alliance for Research
state: California
city: Long Beach
country: United States
facility: Renew Behavioral Health
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: Research Across America
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Santa Rosa
country: United States
facility: Redwood Research Medical Group
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Denver
country: United States
facility: The Mile High Research Center
state: Colorado
city: Hamden
country: United States
facility: Chase Medical Research of Greater New Haven
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Brooksville
country: United States
facility: Meridian Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates
state: Florida
city: Sarasota
country: United States
facility: The Roskamp Institute
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc
state: Georgia
city: Indianapolis
country: United States
facility: IU Health Partners Adult Neurology Clinic
state: Indiana
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Baltimore
country: United States
facility: Pharmasite Research, Inc.
state: Maryland
city: Somerville
country: United States
facility: Alzheimers Disease Center, Quincy Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Springfield Neurology Associates
state: Massachusetts
city: Kalamazoo
country: United States
facility: Borgess Research Institute
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University Medical School /Department of Neurology & Psychiatry
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Manchester
country: United States
facility: Alzheimer's Research Corporation
state: New Jersey
city: Mount Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: Springfield
country: United States
facility: The Cognitive Research Center of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: Memory Enhancement Center of NJ
state: New Jersey
city: West Long Branch
country: United States
facility: Neurology Specialists of Monmouth County
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, LLC
state: New York
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: Manhasset
country: United States
facility: The Litwin-Zucker Research Center
state: New York
city: New Hyde Park
country: United States
facility: Parker Jewish Institute For Health Care & Rehabilitation
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center Comprehensive Center on Brain Aging
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center, LLC
state: New York
city: Orangeburg
country: United States
facility: Nathan S. Kline Institute Geriatric Psychiatry Program
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Charlotte
country: United States
facility: Ani Neurology, PLLC dba Alzheimer's Memory Ctr
state: North Carolina
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Centerville
country: United States
facility: Valley Medical Research
state: Ohio
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Shaker Heights
country: United States
facility: Insight Clinical Trials LLC
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Philadelphia
country: United States
facility: Drexel Neurological Associates
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Franklin
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Austin
country: United States
facility: Senior Adults Specialty Research, Inc
state: Texas
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Richmond
country: United States
facility: National Clinical Research - Richmond, Inc.
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound-Alzhemier's Disease Research Center
state: Washington
Study officials:
affiliation: Cerecin
name: Samuel T Henderson, PhD
role: STUDY_DIRECTOR
References:
citation: Henderson ST, Morimoto BH, Cummings JL, Farlow MR, Walker J. A Placebo-Controlled, Parallel-Group, Randomized Clinical Trial of AC-1204 in Mild-to-Moderate Alzheimer's Disease. J Alzheimers Dis. 2020;75(2):547-557. doi: 10.3233/JAD-191302.