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STEADFAST: Evaluation of the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease

Sponsor
vTv Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT02080364
Collaborator
(none)
880
Enrollment
115
Locations
2
Arms
38
Actual Duration (Months)
7.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 18 months.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
880 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-blind, Placebo Controlled, Multi-center Registration Trial to Evaluate the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease Receiving Acetylcholinesterase Inhibitors and/or Memantine
Actual Study Start Date :
Apr 1, 2015
Actual Primary Completion Date :
Jun 1, 2018
Actual Study Completion Date :
Jun 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Azeliragon 5mg

Azeliragon (TTP488) 5mg orally once daily for 18 months

Drug: Azeliragon
Azeliragon 5mg administered orally, once daily for 18 months
Other Names:
  • TTP488

    		•
    Placebo Comparator: Placebo

    Placebo orally once daily for 18 months

    Drug: Placebo
    Placebo administered orally, once daily for 18 months

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The ADAS-cog is a structured scale (approximately 40 minutes to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis (Rosen, 1984). The ADAS-cog scoring range for the version used in this study is from 0 to 70, with higher scores indicating greater cognitive impairment.

    2. Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The CDR scale is used as a global measure of dementia and is completed by a clinician in the setting of detailed knowledge of the individual patient collected from interviews with the patient and caregiver (Berg, 1988). The CDR describes 5 degrees of impairment in performance on each of 6 categories including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. CDR ratings are 0 for healthy individuals, 0.5 for questionable dementia and 1, 2 and 3 for mild, moderate and severe dementia as defined in the CDR scale. The scores for each category can also be summed and this is known as the sum of box score (CSR-SB). Sum of box scores range from 0 to 18 with higher scores indicating greater cognitive impairment.

    Secondary Outcome Measures

    1. Change From Baseline in Magnetic Resonance Imaging (MRI) Brain Volumetric Measures [Baseline and 18 months]

      Percent of Total Hippocampus Atrophy to Intracranial Volume

    2. Change From Baseline in the Normalized Mean Composite SUVR of the 5 Regions [Baseline to 18 months]

      Extent and severity of brain hypometabolism was assessed centrally at Baseline and Month 18. SUVR PET was designed to make use of FreeSurfer-based segmentations of the brain obtained using the 3DT1 MRI. Following the methods published by Landau and Jagust (Landau SM, Annals of Neurology 2012) and described on the ADNI website (http://adni.loni.usc.edu/methods/pet-analysis-method/), regions were defined in native patient space on the 3DT1 MRI acquired at the Baseline visit and at Month 18 visit. An SUVR measure was computed regionally over five sub-regions (anterior/posterior cingulate, temporal, parietal, frontal and hippocampal areas), normalized to activity in the cerebral white matter. These sub-regions were selected to optimize sensitivity in longitudinal studies. This outcome measure presents the change from baseline in the normalized mean composite SUVR of the 5 regions. A negative change from baseline indicates a decrease (worsening) in brain glucose metabolism/utilization.

    3. Change From Baseline in Alzheimer's Disease Cooperative Study- Activities of Daily Living Inventory (ADCS-ADL) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The ADCS-ADL is an activity of daily living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). Informants are queried via a structured interview format as to whether participants attempted each item in the inventory during the preceding 4 weeks, as well as their level of performance. Scores range from 0-78 with lower scores indicating greater functional impairment.

    4. Change From Baseline in Mini-Mental State Examination (MMSE) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The MMSE is a brief 30-point test that is used to assess cognition (Folstein, 1975). It is commonly used to screen for dementia. In the time span of about 10 minutes, it samples various functions, including arithmetic, memory and orientation. Scores range from 0-30 with lower scores indicating greater cognitive impairment.

    5. Change From Baseline in Neuropsychiatric Inventory (NPI) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with the caregiver (Cummings et al, 1994). It evaluates both the frequency and severity of 12 behavioral areas including delusions, hallucinations, dysphoria (depression) anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, appetite and eating changes and night-time behaviors. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1= mild, 2 = moderate, 3 = severe). Distress is rated by the study partner or caregiver and ranges from 0 (no distress) to 5 (very severe or extreme). The overall score and the score for each subscale are the product of severity and frequency. Scores range from 0-144 with higher scores indicating a greater presence of neuropsychiatric symptoms.

    6. Change From Baseline in Dementia Quality of Life (DEMQOL) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The DEMQOL-Proxy questionnaire is a validated and reliable questionnaire that is interview administered and completed by the caregiver about the patient's health related quality of life (Smith et al, 2005). It consists of 31 items representing 5 domains (daily activities and looking after yourself, health and well-being, cognitive functioning, social relationships, and self-concept) and takes approximately 20 minutes to complete. Scores range 31-124 with higher scores indicate better health related quality of life.

    7. Change From Baseline in Continuous Oral Word Association Task (COWAT) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      The COWAT is a measure of verbal fluency in which the participant is asked to generate orally as many words as possible that begin with the letters "F", "A", and "S", excluding proper names and different forms of the same word. (Borkowski, 1967, Loonstra 2001) For each letter, the participant is allowed one minute to generate the words. Performance is measured by the total number of correct words produced summed across the three letters. Perseverations (i.e., repetitions of a correct word) and intrusions (i.e., words not beginning with the designated letter) are noted.

    8. Change From Baseline in Category Fluency Test (CFT) [Baseline and 18 months (A-Study); baseline and 12 months (B-Study)]

      Study participants are given one minute to provide exemplars of the category 'animals'.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of probable Alzheimer Disease (AD) with documented evidence of progression of disease

    • Mini Mental State Examination (MMSE) score of 21-26, inclusive

    • Clinical Dementia Rating global score of 0.5 or 1

    • Rosen-Modified Hachinski Ischemia Score less than or equal to 4

    • Brain magnetic resonance imaging (MRI) consistent with the diagnosis of probable AD

    • Concurrent use of cholinesterase inhibitor or memantine with stable dose for at least 3 months prior to randomization

    • Caregiver willing to participate and be able to attend clinic visits with patient

    • Ability to ingest oral medications

    Exclusion Criteria:

    • Significant neurological or psychiatric disease other than Alzheimer's disease

    • Participants with evidence or history of severe drug allergies (resulting in dyspnea or severe rash).

    • Any contraindications to MRI (e.g., clinically significant claustrophobia, non-removable ferromagnetic implants). Patients with contraindications to MRI may undergo computed tomography (CT) on approval by sponsor.

    • Any contraindications to the FDG-PET study (e.g. allergy to any component of the FDG dose) in the cohort undergoing a PET scan.

    • Previous exposure to investigational or non-investigational therapies for Alzheimer's disease within 6 months of screening

    • History of cancer within the last 5 years except adequately treated cervical carcinoma in-situ, cutaneous basal cell or squamous cell cancer, or non-progressive prostate cancer not requiring treatment

    • Women of childbearing potential

    • Uncontrolled blood pressure and/or blood pressure above 160/100

    • Prescription medical food intended for dietary management of the metabolic processes associated with Alzheimer's disease.

    • Diagnosis or history of cerebrovascular stroke, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage.

    • Patients with unstable, uncontrolled diabetes (HbA1c > 7.7%) and those requiring insulin.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States 85004
    2 Phoenix Arizona United States 85013
    3 Phoenix Arizona United States 85018
    4 Tucson Arizona United States 85724
    5 Tucson Arizona United States 85741
    6 Bellflower California United States 90706
    7 Costa Mesa California United States 92626
    8 Fullerton California United States 92835
    9 Glendale California United States 91206
    10 Imperial California United States 92251
    11 Irvine California United States 92614
    12 Laguna Hills California United States 92653
    13 Long Beach California United States 90806
    14 Long Beach California United States 90807
    15 Orange California United States 92868
    16 Riverside California United States 92506
    17 San Bernardino California United States 92408
    18 San Francisco California United States 94114
    19 Santa Ana California United States 92705
    20 Atlantis Florida United States 33462
    21 Brooksville Florida United States 34601
    22 Delray Beach Florida United States 33445
    23 Hallandale Beach Florida United States 33009
    24 Hialeah Florida United States 33016
    25 Jacksonville Florida United States 32216
    26 Lake Worth Florida United States 33449
    27 Leesburg Florida United States 34748
    28 Miami Beach Florida United States 33140
    29 Miami Lakes Florida United States 33014
    30 Miami Lakes Florida United States 33016
    31 Miami Florida United States 33122
    32 Miami Florida United States 33137
    33 Orlando Florida United States 32806
    34 Pensacola Florida United States 32503
    35 Sarasota Florida United States 34243
    36 Sunrise Florida United States 33351
    37 Atlanta Georgia United States 30331
    38 Columbus Georgia United States 31909
    39 Chicago Illinois United States 60640
    40 Fairway Kansas United States 66205
    41 Prairie Village Kansas United States 66201
    42 Lexington Kentucky United States 40504
    43 Baltimore Maryland United States 21208
    44 Newton Massachusetts United States 02459
    45 Plymouth Massachusetts United States 02360
    46 Quincy Massachusetts United States 01269
    47 Hattiesburg Mississippi United States 39401
    48 Creve Coeur Missouri United States 63141
    49 Princeton New Jersey United States 08540
    50 Albuquerque New Mexico United States 87109
    51 Albany New York United States 12208
    52 Lake Success New York United States 11042
    53 New York New York United States 10032
    54 Staten Island New York United States 10312
    55 Charlotte North Carolina United States 28270
    56 Raleigh North Carolina United States 27607
    57 Wilmington North Carolina United States 28401
    58 Winston-Salem North Carolina United States 27157
    59 Canton Ohio United States 44718
    60 Shaker Heights Ohio United States 44122
    61 Oklahoma City Oklahoma United States 73103
    62 Oklahoma City Oklahoma United States 73118
    63 Portland Oregon United States 97210
    64 Portland Oregon United States 97225
    65 Media Pennsylvania United States 19063
    66 Norristown Pennsylvania United States 19403
    67 Plains Pennsylvania United States 18705
    68 East Providence Rhode Island United States 02914
    69 East Providence Rhode Island United States 02916
    70 Charleston South Carolina United States 24901
    71 Mount Pleasant South Carolina United States 29464
    72 Cordova Tennessee United States 38018
    73 Nashville Tennessee United States 37203
    74 Dallas Texas United States 75231
    75 San Antonio Texas United States 78229
    76 San Antonio Texas United States 78232
    77 Wichita Falls Texas United States 76309
    78 Murray Utah United States 84123
    79 Kirkland Washington United States 98201
    80 Richland Washington United States 99352
    81 Southport Queensland Australia 4222
    82 Caulfield Victoria Australia 3162
    83 Geelong Victoria Australia 3220
    84 Heidelberg West Victoria Australia 3081
    85 Nedlands Western Australia Australia 6009
    86 West Perth Western Australia Australia 6005
    87 Calgary Alberta Canada T2N 4Z6
    88 Medicine Hat Alberta Canada T1B 4E7
    89 Kentville Nova Scotia Canada B4N4K9
    90 Chatham Ontario Canada N7L 1C1
    91 London Ontario Canada N6C 5J1
    92 Toronto Ontario Canada M3B 257
    93 Gatineau Quebec Canada J8T 8J1
    94 Greenfield Park Quebec Canada J4V2J2
    95 Cork Ireland
    96 Dublin 8 Ireland
    97 Galway Ireland
    98 Christchurch Canterbury New Zealand 8011
    99 Christchurch Canterbury New Zealand 8022
    100 Cape Town South Africa 7405
    101 Cape Town South Africa 7530
    102 Johannesburg South Africa 2196
    103 St. George South Africa 6529
    104 Glasgow United Kingdom G20 OAXA
    105 London United Kingdom W1G 9RU
    106 London United Kingdom WC1X 8QD
    107 Manchester United Kingdom M8 5RB
    108 Northampton United Kingdom NN5 6UD
    109 Oxford United Kingdom OX3 7JX
    110 Penarth United Kingdom CF64 2XX
    111 Preston United Kingdom PR2 9HT
    112 Sheffield United Kingdom S5 7JT
    113 Southhampton United Kingdom SO30 3JB
    114 Swindon United Kingdom SN3 6BW
    115 Warrington United Kingdom WA2 8WA

    Sponsors and Collaborators

    • vTv Therapeutics

    Investigators

    • Study Director: Aaron H Burstein, PharmD, vTv Therapeutics

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    vTv Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02080364
    Other Study ID Numbers:
    • TTP488-301
    First Posted:
    Mar 6, 2014
    Last Update Posted:
    May 7, 2021
    Last Verified:
    May 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by vTv Therapeutics
    Alzheimer's disease
    RAGE
    ADAS-cog
    CDR-sb
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    Participant Flow

    Recruitment Details The A-Study was conducted from April 2015 through April 2018 in the United States and Canada. The B-Study was conducted from September 2016 through June 2018 in the United States, Canada, United Kingdom, Ireland, South Africa, Australia and New Zealand.
    Pre-assignment Detail A total of 1733 subjects underwent screening procedures for determination of eligibility for participation across the A- and B- Studies. 880 subjects were eligible and were randomized and assigned to treatment groups.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Period Title: Baseline Period
    STARTED 197 208 247 228
    COMPLETED 195 206 246 228
    NOT COMPLETED 2 2 1 0
    Period Title: Baseline Period
    STARTED 195 206 246 228
    COMPLETED 148 157 9 4
    NOT COMPLETED 47 49 237 224

    Baseline Characteristics

    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo Total
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily Total of all reporting groups
    Overall Participants 195 206 246 228 875
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    74.6
    (9.13)
    74.9
    (7.96)
    74.9
    (8.55)
    74.4
    (8.64)
    74.7
    (8.56)
    Sex: Female, Male (Count of Participants)
    Female
    97
    49.7%
    91
    44.2%
    107
    43.5%
    107
    46.9%
    402
    45.9%
    Male
    98
    50.3%
    115
    55.8%
    139
    56.5%
    121
    53.1%
    473
    54.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    27
    13.8%
    23
    11.2%
    8
    3.3%
    15
    6.6%
    73
    8.3%
    Not Hispanic or Latino
    168
    86.2%
    183
    88.8%
    238
    96.7%
    213
    93.4%
    802
    91.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.5%
    0
    0%
    0
    0%
    1
    0.1%
    Asian
    5
    2.6%
    2
    1%
    6
    2.4%
    3
    1.3%
    16
    1.8%
    Native Hawaiian or Other Pacific Islander
    2
    1%
    0
    0%
    1
    0.4%
    0
    0%
    3
    0.3%
    Black or African American
    8
    4.1%
    9
    4.4%
    8
    3.3%
    5
    2.2%
    30
    3.4%
    White
    179
    91.8%
    194
    94.2%
    231
    93.9%
    220
    96.5%
    824
    94.2%
    More than one race
    1
    0.5%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    New Zealand
    0
    0%
    0
    0%
    6
    2.4%
    3
    1.3%
    9
    1%
    Canada
    25
    12.8%
    25
    12.1%
    16
    6.5%
    18
    7.9%
    84
    9.6%
    United States
    170
    87.2%
    181
    87.9%
    163
    66.3%
    144
    63.2%
    558
    63.8%
    Ireland
    0
    0%
    0
    0%
    9
    3.7%
    7
    3.1%
    16
    1.8%
    South Africa
    0
    0%
    0
    0%
    24
    9.8%
    22
    9.6%
    46
    5.3%
    United Kingdom
    0
    0%
    0
    0%
    20
    8.1%
    27
    11.8%
    47
    5.4%
    Australia
    0
    0%
    0
    0%
    8
    3.3%
    7
    3.1%
    15
    1.7%
    Apo E4 status (Count of Participants)
    Heterozygous
    83
    42.6%
    79
    38.3%
    115
    46.7%
    105
    46.1%
    382
    43.7%
    Homozygous
    15
    7.7%
    27
    13.1%
    31
    12.6%
    18
    7.9%
    91
    10.4%
    Non-carrier
    95
    48.7%
    98
    47.6%
    96
    39%
    99
    43.4%
    388
    44.3%
    Not reported
    2
    1%
    2
    1%
    4
    1.6%
    6
    2.6%
    14
    1.6%
    Education Level (Count of Participants)
    High School
    61
    31.3%
    65
    31.6%
    86
    35%
    79
    34.6%
    291
    33.3%
    Other (trainings, certifications)
    15
    7.7%
    14
    6.8%
    8
    3.3%
    6
    2.6%
    43
    4.9%
    Some college
    32
    16.4%
    33
    16%
    34
    13.8%
    31
    13.6%
    130
    14.9%
    Associates Degree
    17
    8.7%
    14
    6.8%
    14
    5.7%
    21
    9.2%
    66
    7.5%
    Bachelor's Degree
    44
    22.6%
    39
    18.9%
    64
    26%
    55
    24.1%
    202
    23.1%
    Master's Degree
    21
    10.8%
    26
    12.6%
    29
    11.8%
    25
    11%
    101
    11.5%
    Doctoral Degree
    5
    2.6%
    15
    7.3%
    11
    4.5%
    11
    4.8%
    42
    4.8%
    Background AD Medication (Count of Participants)
    Memantine
    12
    6.2%
    16
    7.8%
    19
    7.7%
    22
    9.6%
    69
    7.9%
    Acetylcholinesterase inhibitor
    117
    60%
    124
    60.2%
    156
    63.4%
    145
    63.6%
    542
    61.9%
    Both Memantine and Acetylcholinesterase inhibitor
    65
    33.3%
    66
    32%
    71
    28.9%
    60
    26.3%
    262
    29.9%
    Not recorded
    1
    0.5%
    0
    0%
    0
    0%
    1
    0.4%
    2
    0.2%
    Years since AD diagnosis (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    2.41
    (2.389)
    2.32
    (2.414)
    2.05
    (1.932)
    1.86
    (1.871)
    2.14
    (2.153)
    Baseline MMSE (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    23.42
    (2.733)
    23.22
    (2.522)
    23.29
    (2.513)
    23.41
    (2.701)
    23.33
    (2.611)
    Baseline ADAS-cog (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    15.42
    (5.186)
    15.51
    (5.427)
    16.94
    (5.623)
    16.08
    (5.295)
    16.05
    (5.424)
    Baseline CDR-Sum of Boxes (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    4.06
    (1.747)
    4.07
    (1.623)
    4.64
    (1.585)
    4.5
    (1.570)
    4.34
    (1.645)
    Baseline ADCS-ADL (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    67.62
    (7.67)
    67.37
    (8.56)
    66.25
    (8.142)
    67.25
    (7.568)
    67.08
    (8.001)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score
    Description The ADAS-cog is a structured scale (approximately 40 minutes to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis (Rosen, 1984). The ADAS-cog scoring range for the version used in this study is from 0 to 70, with higher scores indicating greater cognitive impairment.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. B-Study excludes data from visits occurring after A-Study results announcement on 09 Apr 2018. ADAS-cog was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 138 151 118 121
    Least Squares Mean (Standard Error) [score on a scale]
    3.8
    (0.51)
    3.1
    (0.49)
    3.4
    (0.46)
    2.5
    (0.46)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A-Study: Azeliragon, A-Study: Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3386
    Comments p-value for comparison to Placebo
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection B-Study: Azeliragon, B-Study: Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1992
    Comments p-value for compairons to Placebo
    Method Mixed Models Analysis
    Comments
    2. Primary Outcome
    Title Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-sb)
    Description The CDR scale is used as a global measure of dementia and is completed by a clinician in the setting of detailed knowledge of the individual patient collected from interviews with the patient and caregiver (Berg, 1988). The CDR describes 5 degrees of impairment in performance on each of 6 categories including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. CDR ratings are 0 for healthy individuals, 0.5 for questionable dementia and 1, 2 and 3 for mild, moderate and severe dementia as defined in the CDR scale. The scores for each category can also be summed and this is known as the sum of box score (CSR-SB). Sum of box scores range from 0 to 18 with higher scores indicating greater cognitive impairment.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. B-Study excludes data from visits occurring after A-Study results announcement on 09 Apr 2018. CDR-sb was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 140 150 117 120
    Mean (Standard Deviation) [score on a scale]
    1.4
    (2.23)
    1.4
    (1.85)
    1.3
    (1.87)
    0.7
    (1.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A-Study: Azeliragon, A-Study: Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9394
    Comments p-value for comparison to Placebo.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection B-Study: Azeliragon, B-Study: Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis MMRM model does not converge. LS Mean and p-value are NA.
    3. Secondary Outcome
    Title Change From Baseline in Magnetic Resonance Imaging (MRI) Brain Volumetric Measures
    Description Percent of Total Hippocampus Atrophy to Intracranial Volume
    Time Frame Baseline and 18 months

    Outcome Measure Data

    Analysis Population Description
    Number of subjects with paired Baseline and Month 18 MRIs
    Arm/Group Title Azeliragon 5mg Placebo
    Arm/Group Description Azeliragon (TTP488) 5mg orally once daily for 18 months Azeliragon: Azeliragon 5mg administered orally, once daily for 18 months Placebo orally once daily for 18 months Placebo: Placebo administered orally, once daily for 18 months
    Measure Participants 112 116
    Least Squares Mean (Standard Error) [percentage of Total Hippocampus Atrophy]
    -0.016
    (0.001)
    -0.014
    (0.001)
    4. Secondary Outcome
    Title Change From Baseline in the Normalized Mean Composite SUVR of the 5 Regions
    Description Extent and severity of brain hypometabolism was assessed centrally at Baseline and Month 18. SUVR PET was designed to make use of FreeSurfer-based segmentations of the brain obtained using the 3DT1 MRI. Following the methods published by Landau and Jagust (Landau SM, Annals of Neurology 2012) and described on the ADNI website (http://adni.loni.usc.edu/methods/pet-analysis-method/), regions were defined in native patient space on the 3DT1 MRI acquired at the Baseline visit and at Month 18 visit. An SUVR measure was computed regionally over five sub-regions (anterior/posterior cingulate, temporal, parietal, frontal and hippocampal areas), normalized to activity in the cerebral white matter. These sub-regions were selected to optimize sensitivity in longitudinal studies. This outcome measure presents the change from baseline in the normalized mean composite SUVR of the 5 regions. A negative change from baseline indicates a decrease (worsening) in brain glucose metabolism/utilization.
    Time Frame Baseline to 18 months

    Outcome Measure Data

    Analysis Population Description
    Analyzed as part of an optional FDG-PET substudy
    Arm/Group Title Azeliragon 5mg Placebo
    Arm/Group Description Azeliragon (TTP488) 5mg orally once daily for 18 months Azeliragon: Azeliragon 5mg administered orally, once daily for 18 months Placebo orally once daily for 18 months Placebo: Placebo administered orally, once daily for 18 months
    Measure Participants 38 36
    Least Squares Mean (Standard Error) [SUVR ratio]
    -0.0304
    (0.0039)
    -0.0342
    (0.0039)
    5. Secondary Outcome
    Title Change From Baseline in Alzheimer's Disease Cooperative Study- Activities of Daily Living Inventory (ADCS-ADL)
    Description The ADCS-ADL is an activity of daily living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). Informants are queried via a structured interview format as to whether participants attempted each item in the inventory during the preceding 4 weeks, as well as their level of performance. Scores range from 0-78 with lower scores indicating greater functional impairment.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. B-Study excludes data from visits occurring after A-Study results announcement on 09 Apr 2018. ADCS-ADL was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 141 152 121 122
    Mean (Standard Deviation) [score on a scale]
    -5.1
    (8.63)
    -3.2
    (8.92)
    -5.4
    (8.85)
    -2.8
    (7.83)
    6. Secondary Outcome
    Title Change From Baseline in Mini-Mental State Examination (MMSE)
    Description The MMSE is a brief 30-point test that is used to assess cognition (Folstein, 1975). It is commonly used to screen for dementia. In the time span of about 10 minutes, it samples various functions, including arithmetic, memory and orientation. Scores range from 0-30 with lower scores indicating greater cognitive impairment.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. B-Study excludes data from visits occurring after A-Study results announcement on 09 Apr 2018. MMSE was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 142 153 121 121
    Mean (Standard Deviation) [score on a scale]
    -2.1
    (3.55)
    -2.0
    (3.25)
    -2.1
    (3.25)
    -1.8
    (3.29)
    7. Secondary Outcome
    Title Change From Baseline in Neuropsychiatric Inventory (NPI)
    Description The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with the caregiver (Cummings et al, 1994). It evaluates both the frequency and severity of 12 behavioral areas including delusions, hallucinations, dysphoria (depression) anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, appetite and eating changes and night-time behaviors. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1= mild, 2 = moderate, 3 = severe). Distress is rated by the study partner or caregiver and ranges from 0 (no distress) to 5 (very severe or extreme). The overall score and the score for each subscale are the product of severity and frequency. Scores range from 0-144 with higher scores indicating a greater presence of neuropsychiatric symptoms.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. B-Study excludes data from visits occurring after A-Study results announcement on 09 Apr 2018. NPI was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 142 152 121 122
    Mean (Standard Deviation) [score on a scale]
    -0.2
    (9.77)
    1.3
    (11.53)
    2.3
    (11.24)
    0.0
    (10.67)
    8. Secondary Outcome
    Title Change From Baseline in Dementia Quality of Life (DEMQOL)
    Description The DEMQOL-Proxy questionnaire is a validated and reliable questionnaire that is interview administered and completed by the caregiver about the patient's health related quality of life (Smith et al, 2005). It consists of 31 items representing 5 domains (daily activities and looking after yourself, health and well-being, cognitive functioning, social relationships, and self-concept) and takes approximately 20 minutes to complete. Scores range 31-124 with higher scores indicate better health related quality of life.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. DEMQOL was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 142 152 179 187
    Mean (Standard Deviation) [score on a scale]
    0.0
    (10.2)
    -1.2
    (9.38)
    -0.1
    (10.55)
    -0.8
    (11.70)
    9. Secondary Outcome
    Title Change From Baseline in Continuous Oral Word Association Task (COWAT)
    Description The COWAT is a measure of verbal fluency in which the participant is asked to generate orally as many words as possible that begin with the letters "F", "A", and "S", excluding proper names and different forms of the same word. (Borkowski, 1967, Loonstra 2001) For each letter, the participant is allowed one minute to generate the words. Performance is measured by the total number of correct words produced summed across the three letters. Perseverations (i.e., repetitions of a correct word) and intrusions (i.e., words not beginning with the designated letter) are noted.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. NPI was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 142 153 180 188
    Mean (Standard Deviation) [Total acceptable Words]
    -2.0
    (9.61)
    -0.1
    (8.92)
    -1.8
    (8.12)
    -0.8
    (8.71)
    10. Secondary Outcome
    Title Change From Baseline in Category Fluency Test (CFT)
    Description Study participants are given one minute to provide exemplars of the category 'animals'.
    Time Frame Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (all randomized subjects who receive study medication and have at least one post-baseline efficacy assessment) with Month 18 (A-Study) or Month 12 (B-Study) data. NPI was not reported / not valid for some subject visits; therefore, the number analyzed is smaller than overall number.
    Arm/Group Title A-Study: Azeliragon A-Study: Placebo B-Study: Azeliragon B-Study: Placebo
    Arm/Group Description Azeliragon 5 mg once daily Placebo once daily Azeliragon 5 mg once daily Placebo capsule once daily
    Measure Participants 142 152 180 188
    Mean (Standard Deviation) [Total Acceptable Words]
    -1.7
    (4.45)
    -1.3
    (4.26)
    -1.5
    (3.80)
    9.7
    (146.20)

    Adverse Events

    Time Frame Adverse event reporting commenced when the subject received their first dose and ended at the final study visit (21 months).
    Adverse Event Reporting Description
    Arm/Group Title Azeliragon 5mg Placebo
    Arm/Group Description Azeliragon (TTP488) 5mg orally once daily for 18 months Parts A and B Combined Placebo orally once daily for 18 months Parts A and B Combined
    All Cause Mortality
    Azeliragon 5mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/441 (0.9%) 5/434 (1.2%)
    Serious Adverse Events
    Azeliragon 5mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 70/441 (15.9%) 67/434 (15.4%)
    Cardiac disorders
    Atrial fibrillation 3/441 (0.7%) 4 5/434 (1.2%) 5
    Cardiac failure congestive 2/441 (0.5%) 2 1/434 (0.2%) 2
    Bradycardia 1/441 (0.2%) 1 1/434 (0.2%) 1
    Myocardial infarction 1/441 (0.2%) 1 1/434 (0.2%) 1
    Acute myocardial infarction 1/441 (0.2%) 1 0/434 (0%) 0
    Atrioventricular block complete 1/441 (0.2%) 1 0/434 (0%) 0
    Bundle branch block left 1/441 (0.2%) 1 0/434 (0%) 0
    Sinus bradycardia 0/441 (0%) 0 2/434 (0.5%) 2
    Arrhythmia 0/441 (0%) 0 1/434 (0.2%) 1
    Cardiac arrest 0/441 (0%) 0 1/434 (0.2%) 1
    Myocardial ischaemia 0/441 (0%) 0 1/434 (0.2%) 1
    Endocrine disorders
    Hyperparathyroidism 1/441 (0.2%) 1 0/434 (0%) 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 2/441 (0.5%) 3 1/434 (0.2%) 1
    Gastric ulcer haemorrhage 1/441 (0.2%) 1 1/434 (0.2%) 1
    Colitis 1/441 (0.2%) 1 0/434 (0%) 0
    Gastric polyps 1/441 (0.2%) 1 0/434 (0%) 0
    Gastric ulcer perforation 1/441 (0.2%) 1 0/434 (0%) 0
    Small intestinal obstruction 1/441 (0.2%) 1 0/434 (0%) 0
    Ascites 0/441 (0%) 0 1/434 (0.2%) 1
    Colitis ulcerative 0/441 (0%) 0 1/434 (0.2%) 1
    Intestinal infarction 0/441 (0%) 0 1/434 (0.2%) 1
    Large intestinal obstruction 0/441 (0%) 0 1/434 (0.2%) 1
    Large intestine polyp 0/441 (0%) 0 1/434 (0.2%) 1
    Melaena 0/441 (0%) 0 1/434 (0.2%) 1
    Oesophagitis 0/441 (0%) 0 1/434 (0.2%) 1
    General disorders
    Chest pain 2/441 (0.5%) 2 0/434 (0%) 0
    Pyrexia 2/441 (0.5%) 2 0/434 (0%) 0
    Device dislocation 1/441 (0.2%) 1 0/434 (0%) 0
    Non-cardiac chest pain 0/441 (0%) 0 3/434 (0.7%) 3
    Asthenia 0/441 (0%) 0 1/434 (0.2%) 1
    Hepatobiliary disorders
    Cholelithiasis 0/441 (0%) 0 2/434 (0.5%) 2
    Immune system disorders
    Drug hypersensitivity 0/441 (0%) 0 1/434 (0.2%) 1
    Infections and infestations
    Pneumonia 5/441 (1.1%) 5 4/434 (0.9%) 5
    Diverticulitis 2/441 (0.5%) 2 1/434 (0.2%) 1
    Bronchitis 1/441 (0.2%) 1 1/434 (0.2%) 1
    Sepsis 1/441 (0.2%) 1 1/434 (0.2%) 1
    Urosepsis 1/441 (0.2%) 1 1/434 (0.2%) 1
    Appendicitis perforated 1/441 (0.2%) 1 0/434 (0%) 0
    Cellulitis 1/441 (0.2%) 1 0/434 (0%) 0
    Colonic abscess 1/441 (0.2%) 1 0/434 (0%) 0
    Gastroenteritis viral 1/441 (0.2%) 1 0/434 (0%) 0
    Oesophageal candiasis 1/441 (0.2%) 1 0/434 (0%) 0
    Pneumonia respiratory syncytial viral 1/441 (0.2%) 1 0/434 (0%) 0
    Urinary tract infection 0/441 (0%) 0 2/434 (0.5%) 3
    Clostridium difficile colitis 0/441 (0%) 0 1/434 (0.2%) 1
    Influenza 0/441 (0%) 0 1/434 (0.2%) 1
    Lobar pneumonia 0/441 (0%) 0 1/434 (0.2%) 1
    Orchitis 0/441 (0%) 0 1/434 (0.2%) 1
    Pyelonephritis 0/441 (0%) 0 1/434 (0.2%) 1
    Streptococcal infection 0/441 (0%) 0 1/434 (0.2%) 1
    Injury, poisoning and procedural complications
    Fall 3/441 (0.7%) 3 3/434 (0.7%) 3
    Femoral neck fracture 1/441 (0.2%) 1 2/434 (0.5%) 2
    Rib fracture 1/441 (0.2%) 1 2/434 (0.5%) 2
    Ankle fracture 1/441 (0.2%) 1 0/434 (0%) 0
    Craniocerebral injury 1/441 (0.2%) 1 0/434 (0%) 0
    Jaw fracture 1/441 (0.2%) 1 0/434 (0%) 0
    Pelvic fracture 1/441 (0.2%) 1 0/434 (0%) 0
    Post procedural haematuria 1/441 (0.2%) 1 0/434 (0%) 0
    Post procedural inflammation 1/441 (0.2%) 1 0/434 (0%) 0
    Wrist fracture 1/441 (0.2%) 1 0/434 (0%) 0
    Femur fracture 0/441 (0%) 0 2/434 (0.5%) 2
    Subdural haematoma 0/441 (0%) 0 2/434 (0.5%) 3
    Burns third degree 0/441 (0%) 0 1/434 (0.2%) 1
    Contusion 0/441 (0%) 0 1/434 (0.2%) 1
    Intentional overdose 0/441 (0%) 0 1/434 (0.2%) 1
    Road traffic accident 0/441 (0%) 0 1/434 (0.2%) 1
    Spinal fracture 0/441 (0%) 0 1/434 (0.2%) 1
    Sternal fracture 0/441 (0%) 0 1/434 (0.2%) 1
    Metabolism and nutrition disorders
    Dehydration 2/441 (0.5%) 2 1/434 (0.2%) 1
    Hypernatraemia 1/441 (0.2%) 1 0/434 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthritis 1/441 (0.2%) 1 0/434 (0%) 0
    Intervertebral disc protrusion 1/441 (0.2%) 1 0/434 (0%) 0
    Joint swelling 1/441 (0.2%) 1 0/434 (0%) 0
    Rheumatoid arthritis 1/441 (0.2%) 1 0/434 (0%) 0
    Back pain 0/441 (0%) 0 1/434 (0.2%) 1
    Flank pain 0/441 (0%) 0 1/434 (0.2%) 1
    Rotator cuff syndrome 0/441 (0%) 0 1/434 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma 1/441 (0.2%) 1 1/434 (0.2%) 2
    Colon cancer metastatic 1/441 (0.2%) 1 0/434 (0%) 0
    Invasive ductal breast carcinoma 1/441 (0.2%) 1 0/434 (0%) 0
    Lung cancer metastatic 1/441 (0.2%) 1 0/434 (0%) 0
    Renal cell carcinoma 1/441 (0.2%) 1 0/434 (0%) 0
    Non-Hodgkin's lymphoma 0/441 (0%) 0 1/434 (0.2%) 1
    Pancreatic carcinoma 0/441 (0%) 0 1/434 (0.2%) 1
    Pancreatic carcinoma metastatic 0/441 (0%) 0 1/434 (0.2%) 1
    Nervous system disorders
    Syncope 4/441 (0.9%) 4 4/434 (0.9%) 4
    Dementia Alzheimer's type 2/441 (0.5%) 2 0/434 (0%) 0
    Dizziness 1/441 (0.2%) 1 1/434 (0.2%) 1
    Presyncope 1/441 (0.2%) 1 1/434 (0.2%) 1
    Transient Ischaemic attack 1/441 (0.2%) 1 1/434 (0.2%) 1
    Cerebellar Infarction 1/441 (0.2%) 1 0/434 (0%) 0
    Cerebrovascular Accident 1/441 (0.2%) 1 0/434 (0%) 0
    Dementia 1/441 (0.2%) 1 0/434 (0%) 0
    Haemorrhagic stroke 1/441 (0.2%) 1 0/434 (0%) 0
    Ischaemic stroke 1/441 (0.2%) 1 0/434 (0%) 0
    Nerve root compression 1/441 (0.2%) 1 0/434 (0%) 0
    Amyotrophic lateral sclerosis 0/441 (0%) 0 1/434 (0.2%) 1
    Cerebral haemorrhage 0/441 (0%) 0 1/434 (0.2%) 1
    Encephalopathy 0/441 (0%) 0 1/434 (0.2%) 1
    Hypertensive encephalopathy 0/441 (0%) 0 1/434 (0.2%) 1
    Lethargy 0/441 (0%) 0 1/434 (0.2%) 1
    Subarachnoid haemorrage 0/441 (0%) 0 1/434 (0.2%) 1
    Toxic encephalopathy 0/441 (0%) 0 1/434 (0.2%) 1
    Unresponsive to stimuli 0/441 (0%) 0 1/434 (0.2%) 1
    Psychiatric disorders
    Aggression 1/441 (0.2%) 2 0/434 (0%) 0
    Agitation 1/441 (0.2%) 1 0/434 (0%) 0
    Anxiety 1/441 (0.2%) 1 0/434 (0%) 0
    Mental status changes 1/441 (0.2%) 1 0/434 (0%) 0
    Major depression 0/441 (0%) 0 1/434 (0.2%) 1
    Suicidal ideation 0/441 (0%) 0 1/434 (0.2%) 1
    Renal and urinary disorders
    Nephrolithiasis 1/441 (0.2%) 1 0/434 (0%) 0
    Renal failure acute 1/441 (0.2%) 1 0/434 (0%) 0
    Renal injury 1/441 (0.2%) 1 0/434 (0%) 0
    Calculus urinary 0/441 (0%) 0 1/434 (0.2%) 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/441 (0%) 0 1/434 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 2/441 (0.5%) 2 1/434 (0.2%) 1
    Pneumonia aspiration 2/441 (0.5%) 2 1/434 (0.2%) 1
    Asthma 1/441 (0.2%) 1 0/434 (0%) 0
    Pulmonary embolism 1/441 (0.2%) 1 0/434 (0%) 0
    Respiratory failure 1/441 (0.2%) 2 0/434 (0%) 0
    Acute respiratory failure 0/441 (0%) 0 1/434 (0.2%) 1
    Vascular disorders
    Deep vein thrombosis 1/441 (0.2%) 1 1/434 (0.2%) 1
    Aortic stenosis 1/441 (0.2%) 1 0/434 (0%) 0
    Hypertension 1/441 (0.2%) 1 0/434 (0%) 0
    Hypovolaemic shock 1/441 (0.2%) 1 0/434 (0%) 0
    Hypotension 0/441 (0%) 0 1/434 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    Azeliragon 5mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 320/441 (72.6%) 324/434 (74.7%)
    Cardiac disorders
    Atrial Fibrillation 5/441 (1.1%) 7 7/434 (1.6%) 8
    Gastrointestinal disorders
    Diarrhoea 17/441 (3.9%) 18 20/434 (4.6%) 22
    Nausea 14/441 (3.2%) 14 10/434 (2.3%) 10
    Constipation 10/441 (2.3%) 10 8/434 (1.8%) 8
    General disorders
    Fatigue 13/441 (2.9%) 16 14/434 (3.2%) 15
    Infections and infestations
    Urinary tract infection 45/441 (10.2%) 47 33/434 (7.6%) 33
    Nasopharyngitis 19/441 (4.3%) 19 23/434 (5.3%) 24
    Upper Respiratory Tract Infection 20/441 (4.5%) 23 16/434 (3.7%) 17
    Bronchitis 9/441 (2%) 9 14/434 (3.2%) 14
    Sinusitis 9/441 (2%) 9 9/434 (2.1%) 9
    Influenza 7/441 (1.6%) 7 11/434 (2.5%) 11
    Injury, poisoning and procedural complications
    Fall 48/441 (10.9%) 59 55/434 (12.7%) 59
    Laceration 10/441 (2.3%) 10 11/434 (2.5%) 13
    Contusion 8/441 (1.8%) 9 8/434 (1.8%) 12
    Investigations
    Weight Decreased 17/441 (3.9%) 17 13/434 (3%) 13
    Metabolism and nutrition disorders
    Decreased Appetite 5/441 (1.1%) 5 9/434 (2.1%) 9
    Musculoskeletal and connective tissue disorders
    Back pain 10/441 (2.3%) 11 14/434 (3.2%) 14
    Musculoskeletal Pain 10/441 (2.3%) 10 5/434 (1.2%) 5
    Arthralgia 9/441 (2%) 9 14/434 (3.2%) 16
    Nervous system disorders
    Dizziness 18/441 (4.1%) 19 15/434 (3.5%) 15
    Headache 15/441 (3.4%) 16 19/434 (4.4%) 19
    Syncope 7/441 (1.6%) 8 5/434 (1.2%) 5
    Psychiatric disorders
    Depression 21/441 (4.8%) 21 20/434 (4.6%) 20
    Agitation 14/441 (3.2%) 16 17/434 (3.9%) 18
    Anxiety 10/441 (2.3%) 11 15/434 (3.5%) 15
    Insomnia 11/441 (2.5%) 11 7/434 (1.6%) 7
    Respiratory, thoracic and mediastinal disorders
    Cough 13/441 (2.9%) 13 9/434 (2.1%) 9
    Vascular disorders
    Hypertension 10/441 (2.3%) 10 14/434 (3.2%) 14

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Where PI requires the use of the Study Results for publication, the PI shall seek the Sponsor's written approval which shall not be unreasonably withheld; provided, however, that (i) Sponsor may require removal of any Confidential Information of Sponsor or may delay publication for a reasonable period of time in order to secure protection any IP Rights; and, (ii) as the Study is designed as a multi-center Study, no publication shall be made until after the first multi-center publication.

    Results Point of Contact

    Name/Title Ann Gooch PhD,RAC,CCRP; Vice President Clinical Development & Regulatory Operations
    Organization vTv Therapeutics LLC
    Phone 336-841-0300 ext 80544
    Email agooch@vtvtherapeutics.com
    Responsible Party:
    vTv Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02080364
    Other Study ID Numbers:
    • TTP488-301
    First Posted:
    Mar 6, 2014
    Last Update Posted:
    May 7, 2021
    Last Verified:
    May 1, 2021