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Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease (COGNITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02547818
Recruitment Status : Completed
First Posted : September 11, 2015
Last Update Posted : November 10, 2021
PharmaConsulting Group
APCER Life Sciences
Information provided by (Responsible Party):
AZTherapies, Inc.

Brief Summary:
This is a global Phase III, randomized, double-blinded, placebo-controlled study for subjects with evidence of early AD. The protocol is designed to determine whether ALZT-OP1 combination treatment (ALZT-OP1a + ALZT-OP1b) will slow down, arrests, or reverse cognitive and functional decline, in subjects with evidence of early stage Alzheimer's disease (AD).

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: ALZT-OP1a Drug: ALZT-OP1b Other: Placebo ALZT-OP1a Other: Placebo ALZT-OP1b Phase 3

Detailed Description:

This Phase III study is designed as a randomized, double-blinded, placebo-controlled study for subjects with evidence of early AD. The study will evaluate safety and tolerability, efficacy as measured by CDR-SB, and will determine if the combination therapy ALZT-OP1 will slow down, arrests, or reverse cognitive and functional decline in an early stage AD population.

Subjects will be randomly assigned to one of four treatment arms: Group I will consist of ALZT-OP1a (cromolyn) for inhalation, plus an oral placebo tablet; OR the Group II arm, which will consist of ALZT-OP1 combination therapy ALZT-OP1a (cromolyn) for inhalation, plus ALZT-OP1b (ibuprofen) tablet for oral administration; OR to the Group III arm, which will consist of inhaled placebo, plus ALZT-OP1b (ibuprofen) tablet for oral administration; OR to the Group IV placebo arm, which will consist of inhaled placebo plus an oral placebo tablet.

A minimum of 400 evaluable subjects will be randomized to receive one of four possible treatment assignments containing various combinations of active study drug or placebo.

To account for subject dropouts (estimated rate of 30%), it is anticipated that up to 600 (or 150 subjects per treatment arm) may be recruited and randomized, to achieve a minimum of 100 evaluable subjects per treatment arm.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 620 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Actual Study Start Date : September 15, 2015
Actual Primary Completion Date : November 13, 2020
Actual Study Completion Date : November 18, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Group I
ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.
Drug: ALZT-OP1a
1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory
Other Name: Cromolyn

Other: Placebo ALZT-OP1b
Non-active tablets

Active Comparator: Group II
ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration.
Drug: ALZT-OP1a
1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory
Other Name: Cromolyn

Drug: ALZT-OP1b
Other Name: Ibuprofen

Active Comparator: Group III
ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration.
Drug: ALZT-OP1b
Other Name: Ibuprofen

Other: Placebo ALZT-OP1a
Non-active capsules

Placebo Comparator: Group IV
ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration.
Other: Placebo ALZT-OP1a
Non-active capsules

Other: Placebo ALZT-OP1b
Non-active tablets

Primary Outcome Measures :
  1. Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline and Week 72 ]
    The combination active treatment group will be compared to each of the single component groups, including the placebo group, the mean change from Baseline to Week 72 will be quantified.

Secondary Outcome Measures :
  1. Number of Treatment Emergent Adverse Events (TEAE) [ Time Frame: 72 weeks ]
    Safety will be evaluated based on the number, type, and frequency of treatment emergent adverse events. They will be individually presented for all subjects in data listings, and summarized in tables by treatment group and by treatment assignment. The AE's will be summarized and reported collectively based on information obtained through physical examination, ECG, and laboratory findings captured after dosing is initiated.

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 55-79 years old;
  • ≥ 8 years of education;
  • Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol;
  • Evidence of early AD, as defined by all of the following:

    1. Memory complaint by subject or study partner that is verified by a study partner;
    2. Objective memory impairment for age, documented by scoring below the education adjusted cutoff of the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale Third Edition (the maximum score is 25):

      • ≤ 8 for 16 or more years of education, or
      • ≤ 4 for 8-15 years of education;
      • Essentially preserved general cognitive function;
      • Largely intact functional activities;
      • Not demented;
  • Cerebrospinal fluid (CSF) biomarker results consistent with early AD, including CSF Aβ-42 levels ≥ 180 pg/mL and ≤ 690 pg/mL;
  • Clinical Dementia Rating (Global) = 0.5; Memory Box score must be at least 0.5;
  • Must be fluent in the language of the cognitive testing material being administered;
  • Stability of permitted medications for 4 weeks prior to study start; subjects receiving acetylcholinesterase inhibitors and/or memantine should be on stable dose of those medications for at least 12 weeks prior to study start with every effort to maintain stable dose for the duration of the study;
  • Visual and auditory acuity adequate for neuropsychological testing;
  • Good general health with no diseases expected to interfere with the study;
  • Must provide written informed consent for APOe4 genotype testing;
  • Must provide written informed consent for CSF sampling.

Exclusion Criteria:

  • Any significant neurological disease other than suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities;
  • Major depressive episode, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) within the past 6 months, which could lead to difficulty complying with the protocol;
  • History of schizophrenia or bipolar disorder (DSM-IV criteria);
  • History of alcohol or substance abuse or dependence within the past 3 years (DSM-IV criteria);
  • Currently taking medications that could lead to difficulty complying with the protocol; subjects must be on a stable dose of current medications for 4 weeks prior to study entry, with the exception of acetylcholinesterase inhibitors and/or memantine, which must be on a stable dose for at least 12 weeks prior to study entry;
  • Investigational agents are prohibited one month prior to entry and for the duration of the trial;
  • Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
  • Currently taking cromolyn, or have taken cromolyn, within the past 12 months;
  • Chronic daily use of high-dose NSAID for osteoarthritis, rheumatoid arthritis, or other chronic inflammatory diseases ("chronic" defined as 3200 mg/day for >2 weeks);
  • Chronic daily use of aspirin exceeding standard of care guidelines for low dose aspirin therapy for prevention of stroke and/or other recommended uses;
  • Allergy to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®, etc.);
  • Allergies to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin;
  • Clinically significant respiratory disorders with impaired respiratory effort or difficulty taking inhaled drugs;
  • Uncontrolled chronic asthma;
  • Abnormal pulmonary function test, defined for this protocol as: FEV1/FVC < predicted value for subject AND FEV1 < 70% of predicted value, indicating moderate or severe respiratory obstruction;
  • Taking inhaled protein products on a chronic basis;
  • Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol;
  • Pregnancy or lactation for female subjects of child-bearing potential (i.e., < two years post-menopausal or not surgically sterile);
  • For sexually active male subjects, unwillingness or incapability of using appropriate contraception methods;
  • Severe renal or hepatic impairment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02547818

Hide Hide 121 study locations
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United States, Arizona
Cognitive Clinical Trials
Gilbert, Arizona, United States, 85296
Phoenix, Arizona, United States, 85004
Cognitive Clinical Trials
Scottsdale, Arizona, United States, 85251
Territory Neurology & Research Institute
Tucson, Arizona, United States, 85704
United States, California
Alliance Research Center
Laguna Hills, California, United States, 92653
Renew Behavioral Health
Long Beach, California, United States, 90807
Excell Research, Inc.
Oceanside, California, United States, 92056
University of California Irvine School of Medicine
Orange, California, United States, 92868
Asclepes Research Center
Panorama City, California, United States, 91402
Artemis Clinical Research
Riverside, California, United States, 92503
Riverside, California, United States, 92506
Northern California Research
Sacramento, California, United States, 95821
Syrentys Clinical Research
Santa Ana, California, United States, 92705
United States, Colorado
Mile High Research Center
Denver, Colorado, United States, 80218
United States, Florida
TOPAZ Clinical Research
Apopka, Florida, United States, 32703
Parkinson's Disease & Movement Disorders Center of Boca Raton
Boca Raton, Florida, United States, 33486
Bradenton Research Center
Bradenton, Florida, United States, 34205
Finlay Medical Research Group
Greenacres City, Florida, United States, 33467
Galiz Clinical Research
Hialeah, Florida, United States, 33016
Miami Lakes, Florida, United States, 33014
The Neurology Research Group
Miami, Florida, United States, 22176
Premier Clinical Research Institute
Miami, Florida, United States, 33122
Finlay Medical Research Group
Miami, Florida, United States, 33126
Next Phase Research Alliance - Cano Health
Miami, Florida, United States, 33144
IMIC, Inc.
Miami, Florida, United States, 33157
Next Phase Research Alliance - MetroMed
Miami, Florida, United States, 33186
Next Phase Research Alliance
Miami, Florida, United States, 33186
CNS Healthcare
Orlando, Florida, United States, 32801
Pines Care Research Center
Pembroke Pines, Florida, United States, 33026
Neurostudies, Inc.
Port Charlotte, Florida, United States, 33952
Progressive Medical Research
Port Orange, Florida, United States, 32127
Axiom Clinical Research
Tampa, Florida, United States, 33609
Stedman Clinical Trials
Tampa, Florida, United States, 33613
United States, Georgia
Columbus Research & Wellness Institute
Columbus, Georgia, United States, 31904
United States, Illinois
Behavioral Health Care Associates
Schaumburg, Illinois, United States, 60193
United States, Maine
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
Coastal Health Care
Freeport, Maine, United States, 04032
United States, Maryland
Samuel and Alexia Bratton Memory Clinic
Easton, Maryland, United States, 21601
United States, Massachusetts
ActivMed Practices & Research, Inc.
Methuen, Massachusetts, United States, 01844
The Alzheimer's Disease Center
Quincy, Massachusetts, United States, 02169
United States, Michigan
Bronson Neurobehavioral Health
Paw Paw, Michigan, United States, 49079
United States, Nebraska
Cognitive Clinical Trials
Bellevue, Nebraska, United States, 68005
Cognitive Clinical Trials
Omaha, Nebraska, United States, 68007
United States, New Hampshire
ActivMed Practices & Research Inc.
Portsmouth, New Hampshire, United States, 03801
United States, New Jersey
Memory Enhancement Center of America
Eatontown, New Jersey, United States, 07724
AdvancedMed Research
Lawrenceville, New Jersey, United States, 08648
The NeuroCognitive Institute
Mount Arlington, New Jersey, United States, 07856
United States, New Mexico
Albuquerque Neuroscience
Albuquerque, New Mexico, United States, 87109
United States, New York
Adirondack Medical Research Center
Glens Falls, New York, United States, 12801
Manhattan Behavioral Medicine
New York, New York, United States, 10023
Medical Research Network
New York, New York, United States, 10128
Nathan S. Kline Institute for Psychiatric Research
New York, New York, United States, 10128
Winifred Masterson Burke Medical Research Institute
White Plains, New York, United States, 10605
United States, North Carolina
ANI Neurology, PLLC Alzheimer's Memory Center
Charlotte, North Carolina, United States, 28270
Raleigh Neurological Associates
Raleigh, North Carolina, United States, 27607
PMG Winston-Salem
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Insight Clincial Trials
Shaker Heights, Ohio, United States, 44122
United States, Oklahoma
Cutting Edge Research Group
Oklahoma City, Oklahoma, United States, 73116
Tulsa Clinical Research, Inc.
Tulsa, Oklahoma, United States, 74114
United States, Pennsylvania
Pearl Clinical Research
Norristown, Pennsylvania, United States, 19401
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Palmetto Health
Columbia, South Carolina, United States, 29044
Metrolina Neurological Associates, PA
Rock Hill, South Carolina, United States, 29732
United States, Tennessee
CNS Healthcare
Memphis, Tennessee, United States, 38119
United States, Texas
Neurology Associates of Arlington, P.A.
Mansfield, Texas, United States, 76063
Grayline Clinical Drug Trials
Wichita Falls, Texas, United States, 76309
United States, Utah
Wasatch Clinical Research, LLC
Salt Lake City, Utah, United States, 84107
United States, Washington
Kingfisher Cooperative
Spokane, Washington, United States, 99202
Australia, New South Wales
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
KaRa Institute of Neurological Diseases
Macquarie Park, New South Wales, Australia, 2113
Australia, Queensland
Pacific Private Clinic
Southport, Queensland, Australia, 4215
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Geelong Private Medical Centre
Geelong, Victoria, Australia, 3220
Austin Health
Heidelberg, Victoria, Australia, 3081
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
UMBAL "Dr. Georgi Stranski" EAD
Pleven, Bulgaria, 5800
MHAT "Central Onco Hospital" Ltd.
Plovdiv, Bulgaria, 4000
Ruse, Bulgaria, 7002
"First MHAT - Sofia" EAD
Sofia, Bulgaria, 1154
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD
Sofia, Bulgaria, 1431
Canada, British Columbia
Medical Arts Health Research
Penticton, British Columbia, Canada, V2A 5L5
Medical Arts Health Research
West Vancouver, British Columbia, Canada, V7T 1C5
Canada, Britsh Columbia
Okanagan Clinical Trials
Kelowna, Britsh Columbia, Canada, V1Y 1Z9
Canada, Montreal
Montreal Neurological Research Institute
Québec, Montreal, Canada, H3A 284
Canada, Nova Scotia
True North Clinical Research
Halifax, Nova Scotia, Canada, B3S 1M7
True North Clinical Research
Kentville, Nova Scotia, Canada, B4N 4K9
Canada, Ontario
JBN Medical
Burlington, Ontario, Canada, L7M 4Y1
Chatham-Kent Clinical Trials
Chatham, Ontario, Canada, N7l1C1
The Centre for Memory and Aging
East York, Ontario, Canada, M4G 3E8
Canada, Quebec
Cliniuqe de la Memoire de l'Outouais
Gatineau, Quebec, Canada, J8T 8J1
Neurosanatio, s.r.o.
Litomyšl, Czech Republic, Czechia, 570 01
Neurologie MU - Ondrej Koci, s.r.o.
Novy Bor, Czech Republic, Czechia, 473 01
CT Center MaVfe, s.r.o
Olomouc, Czech Republic, Czechia, 779 00
Vestra Clinics, s.r.o.
Rychnov Nad Kněžnou, Czech Republic, Czechia, 516 01
NEUROHK, s.r.o.
Chocen, Czechia, 565 01
Clinline Services s.r.o.
Hostivice, Czechia, 253 01
Psychiatricka ambulance
Hradec Kralove, Czechia, 503 41
Psychiatricka ambulance Supervize s.r.o.
Kutná Hora, Czechia, 28401
Krajska nemocnice Liberec a.s.
Liberec, Czechia, 460 63
A-shine, s.r.o.
Plzen, Czechia, 312 00
Praha, Czechia, 100 00
Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol
Praha, Czechia, 150 06
INEP medical s.r.o.
Praha, Czechia, 186 00
Neurologia Klinika Semmelweis Egyetem
Budapest, Hungary, H-1083
Orszagos Klinikai Idegtudomanyi Intezat
Budapest, Hungary, H-1145
Vaszary Kolos Korhaz
Esztergom, Hungary, H-2500
Bekes Megyei Pandy Kalman Korhaz
Gyula, Hungary, H-5700
Petz Aladar Megyei Oktato Korhaz
Győr, Hungary, 09024
Cermed Pawel Hernik
Bialystok, Poland, 15-270
Podlaskie Centrum Psychogeriatrii
Bialystok, Poland, 15-756
Przychondnia Srodmiescie
Bydgoszcz, Poland, 85-080
Centrum Medyczne KERMED
Bydgoszcz, Poland, 85-231
Szpital Powiatowy w Czeladzi
Czeladz, Poland, 41-250
Centrum Zdrowia Psychicznego Biomed - Jan Latala
Kielce, Poland, 25-411
Centrum Medyczne Plejady
Kraków, Poland, 30-363
Centrum Opieki Zdrowotnej Orkan-Med
Ksawerow, Poland, 95-054
Centrum Medyczne im. Dr Karola Jonschera w Lodzi
Lodz, Poland, 93-113
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, Poland, 20-954
CRC Sp. Zo.o.
Poznan, Poland, 60-856
Euromedis Sp. Zo.o
Szczecin, Poland, 70-111
Sponsors and Collaborators
AZTherapies, Inc.
PharmaConsulting Group
APCER Life Sciences
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Study Director: David R. Elmaleh, PhD AZTherapies, Inc.
Additional Information:
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Responsible Party: AZTherapies, Inc. Identifier: NCT02547818    
Other Study ID Numbers: AZT-001
First Posted: September 11, 2015    Key Record Dates
Last Update Posted: November 10, 2021
Last Verified: November 2020
Keywords provided by AZTherapies, Inc.:
Early stage AD
Memory loss
Memory problems
Early Alzheimer's Disease
Early AD
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action