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Efficacy and Safety of T-817MA in Patients With Mild to Moderate Alzheimer's Disease (US202)

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.
 
ClinicalTrials.gov Identifier: NCT02079909
Recruitment Status : Completed
First Posted : March 6, 2014
Results First Posted : August 9, 2018
Last Update Posted : February 26, 2019
Sponsor:
Collaborator:
Alzheimer's Disease Cooperative Study (ADCS)
Information provided by (Responsible Party):
FUJIFILM Toyama Chemical Co., Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: T-817MA-H
Drug: T-817MA-L
Drug: Placebo
Enrollment 482
Recruitment Details  
Pre-assignment Details  
Arm/Group Title T-817MA-H T-817MA-L Placebo
Hide Arm/Group Description

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

Period Title: Overall Study
Started 158 166 158
Completed 120 117 140
Not Completed 38 49 18
Reason Not Completed
Adverse Event             23             23             7
Withdrawal by Subject             9             17             4
Lost to Follow-up             2             3             1
Death             2             2             0
Lack of Efficacy             0             0             1
Protocol Violation             0             1             1
Physician Decision             0             1             1
Relocation etc.             2             2             3
Arm/Group Title T-817MA-H T-817MA-L Placebo Total
Hide Arm/Group Description

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

Total of all reporting groups
Overall Number of Baseline Participants 154 159 156 469
Hide Baseline Analysis Population Description
The overall numbers of baseline participants display patient numbers in the mITT population, the primary analysis population. The mITT population excludes patients who did not take any study drug or did not perform any efficacy evaluation post-baseline. Thus, the numbers are slightly difference from the ones in the participant flow.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 154 participants 159 participants 156 participants 469 participants
71.8  (7.8) 71.9  (8.2) 71.8  (7.5) 71.9  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 159 participants 156 participants 469 participants
Female
82
  53.2%
81
  50.9%
89
  57.1%
252
  53.7%
Male
72
  46.8%
78
  49.1%
67
  42.9%
217
  46.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 159 participants 156 participants 469 participants
American Indian or Alaska Native
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.2%
Asian
3
   1.9%
3
   1.9%
2
   1.3%
8
   1.7%
Native Hawaiian or Other Pacific Islander
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
8
   5.2%
7
   4.4%
11
   7.1%
26
   5.5%
White
140
  90.9%
146
  91.8%
142
  91.0%
428
  91.3%
More than one race
0
   0.0%
1
   0.6%
1
   0.6%
2
   0.4%
Unknown or Not Reported
2
   1.3%
1
   0.6%
0
   0.0%
3
   0.6%
ApoE4 genotype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 159 participants 156 participants 469 participants
Non-carriers
54
  35.1%
57
  35.8%
50
  32.1%
161
  34.3%
Heterozygotes
55
  35.7%
74
  46.5%
71
  45.5%
200
  42.6%
Homozygotes
32
  20.8%
21
  13.2%
27
  17.3%
80
  17.1%
Unknown
13
   8.4%
7
   4.4%
8
   5.1%
28
   6.0%
MMSE   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 154 participants 159 participants 156 participants 469 participants
18.4  (3.9) 18.2  (3.8) 18.2  (3.8) 18.3  (3.8)
[1]
Measure Description: The Mini Mental Scale Examination (MMSE) is a validated, brief, frequently used screening instrument for Alzheimer's disease drug studies. The MMSE scale evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. The MMSE is scored as the number of correctly completed items with a lower score indicative of poorer performance and greater cognitive impairment. The total score ranges from 0 (worse) to 30 (perfect performance).
1.Primary Outcome
Title ADAS-cog Change From Baseline to Week 52
Hide Description The ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained. The test is scored in terms of errors, with higher scores reflecting poorer performance and greater impairment. Scores can range from 0 (best) to 70 (worse).
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants display the numbers of patients who were included in the mITT population and had baseline and at least one post-baseline ADAS-cog evaluation.
Arm/Group Title T-817MA-H T-817MA-L Placebo
Hide Arm/Group Description:

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

Overall Number of Participants Analyzed 117 115 137
Mean (Standard Error)
Unit of Measure: units on a scale
7.08  (0.756) 7.45  (0.756) 7.91  (0.727)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T-817MA-H, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3919
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.84
Estimation Comments [Not Specified]
2.Primary Outcome
Title CGIC
Hide Description The ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) is a validated categorical measure of change in the patient's clinical condition between baseline and follow-up visits. It measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination of the patient and an interview of the study partner. A skilled and experienced clinician who is blinded to treatment assignment rates the patient on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). It is suggested that the instrument has distinct clinical utility in assessing change in AD clinical trials.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants display the numbers of patients who were included in the mITT population and had at least one post-baseline CGIC evaluation.
Arm/Group Title T-817MA-H T-817MA-L Placebo
Hide Arm/Group Description:

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

Overall Number of Participants Analyzed 118 116 138
Mean (Standard Error)
Unit of Measure: units on a scale
5.25  (0.1) 5.24  (0.1) 5.22  (0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T-817MA-H, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7588
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Estimation Comments [Not Specified]
3.Secondary Outcome
Title ADCS-ADL Change From Baseline to Week 52
Hide Description The ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) is a validated tool for assessing instrumental and basic activities of daily living based on a 23-item structured interview of the study partner. The scale has a range of 0 to 78, with lower scores indicating greater impairment.
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants display the numbers of patients who were included in the mITT population and had baseline and at least one post-baseline ADCS-ADL evaluation.
Arm/Group Title T-817MA-H T-817MA-L Placebo
Hide Arm/Group Description:

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

Overall Number of Participants Analyzed 118 118 140
Mean (Standard Error)
Unit of Measure: units on a scale
-10.01  (0.991) -11.07  (0.992) -11.29  (0.957)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T-817MA-H, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3212
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.29
Estimation Comments [Not Specified]
Time Frame 52weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title T-817MA-H T-817MA-L Placebo
Hide Arm/Group Description

224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.

T-817MA-H: 224 mg or 448 mg T-817 MA once daily

224 mg T-817MA once daily

T-817MA-L: 224 mg T-817 MA once daily

Placebo once daily

Placebo: Placebo

All-Cause Mortality
T-817MA-H T-817MA-L Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/158 (1.27%)   2/166 (1.20%)   0/158 (0.00%) 
Hide Serious Adverse Events
T-817MA-H T-817MA-L Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/158 (16.46%)   25/166 (15.06%)   20/158 (12.66%) 
Blood and lymphatic system disorders       
Anaemia Macrocytic *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Cardiac disorders       
Acute Myocardial Infarction *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Atrial Fibrillation *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Atrioventricular Block Complete *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Bradycardia *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Cardiac Arrest *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Myocardial Infarction *  1/158 (0.63%)  1/166 (0.60%)  1/158 (0.63%) 
Ear and labyrinth disorders       
Vertigo Positional *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Gastrointestinal disorders       
Diarrhoea *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Duodenal Ulcer Haemorrhage *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Megacolon *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Pancreatitis *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Pancreatitis Acute *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
General disorders       
Asthenia *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Chest Pain *  0/158 (0.00%)  2/166 (1.20%)  1/158 (0.63%) 
Non-Cardiac Chest Pain *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Hepatobiliary disorders       
Cholelithiasis *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Hepatitis *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Infections and infestations       
Cellulitis *  2/158 (1.27%)  0/166 (0.00%)  0/158 (0.00%) 
Clostridium Difficile Infection *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Cystitis *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Diverticulitis *  1/158 (0.63%)  1/166 (0.60%)  0/158 (0.00%) 
Gastroenteritis *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Pneumonia *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Pneumonia Influenzal *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Sepsis *  0/158 (0.00%)  2/166 (1.20%)  0/158 (0.00%) 
Urinary Tract Infection *  2/158 (1.27%)  1/166 (0.60%)  1/158 (0.63%) 
Injury, poisoning and procedural complications       
Fall *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Femoral Neck Fracture *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Femur Fracture *  1/158 (0.63%)  1/166 (0.60%)  0/158 (0.00%) 
Hip Fracture *  0/158 (0.00%)  1/166 (0.60%)  1/158 (0.63%) 
Humerus Fracture *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Joint Injury *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Laceration *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Multiple Fractures *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Post Procedural Haemorrhage *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Rib Fracture *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Subdural Haematoma *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Metabolism and nutrition disorders       
Dehydration *  2/158 (1.27%)  2/166 (1.20%)  0/158 (0.00%) 
Hypokalaemia *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Musculoskeletal and connective tissue disorders       
Chondrocalcinosis Pyrophosphate *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma of Colon *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Breast Cancer *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Breast Cancer Metastatic *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Nervous system disorders       
Altered State of Consciousness *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Cerebral Haematoma *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Cerebral Haemorrhage *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Cerebrovascular Accident *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Hydrocephalus *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Loss of Consciousness *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Syncope *  0/158 (0.00%)  2/166 (1.20%)  3/158 (1.90%) 
Transient Ischaemic Attack *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Psychiatric disorders       
Abnormal Behaviour *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Agitation *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Completed Suicide *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Confusional State *  1/158 (0.63%)  1/166 (0.60%)  0/158 (0.00%) 
Delirium *  3/158 (1.90%)  1/166 (0.60%)  1/158 (0.63%) 
Mental Status Changes *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Paranoia *  1/158 (0.63%)  0/166 (0.00%)  0/158 (0.00%) 
Renal and urinary disorders       
Renal Failure *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Urinary Retention *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Reproductive system and breast disorders       
Vaginal Haemorrhage *  0/158 (0.00%)  1/166 (0.60%)  0/158 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary Embolism *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
Pulmonary Oedema *  0/158 (0.00%)  0/166 (0.00%)  1/158 (0.63%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
T-817MA-H T-817MA-L Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   132/158 (83.54%)   133/166 (80.12%)   119/158 (75.32%) 
Gastrointestinal disorders       
Diarrhoea *  49/158 (31.01%)  34/166 (20.48%)  20/158 (12.66%) 
Nausea *  9/158 (5.70%)  13/166 (7.83%)  6/158 (3.80%) 
Vomiting *  9/158 (5.70%)  8/166 (4.82%)  7/158 (4.43%) 
Infections and infestations       
Nasopharyngitis *  4/158 (2.53%)  4/166 (2.41%)  9/158 (5.70%) 
Urinary tract infection *  21/158 (13.29%)  17/166 (10.24%)  22/158 (13.92%) 
Injury, poisoning and procedural complications       
Fall *  12/158 (7.59%)  14/166 (8.43%)  17/158 (10.76%) 
Investigations       
Weight decreased *  8/158 (5.06%)  4/166 (2.41%)  3/158 (1.90%) 
Nervous system disorders       
Dizziness *  11/158 (6.96%)  7/166 (4.22%)  3/158 (1.90%) 
Headache *  9/158 (5.70%)  16/166 (9.64%)  10/158 (6.33%) 
Psychiatric disorders       
Agitation *  4/158 (2.53%)  5/166 (3.01%)  14/158 (8.86%) 
Anxiety *  7/158 (4.43%)  9/166 (5.42%)  12/158 (7.59%) 
Depression *  8/158 (5.06%)  6/166 (3.61%)  7/158 (4.43%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Project Manager
Organization: FUJIFILM Toyama Chemical
Phone: +81-3-6427-6245
EMail: fftc-clinicaltrial-info1@fujifilm.com
Layout table for additonal information
Responsible Party: FUJIFILM Toyama Chemical Co., Ltd.
ClinicalTrials.gov Identifier: NCT02079909    
Other Study ID Numbers: T817MAUS202
First Submitted: March 4, 2014
First Posted: March 6, 2014
Results First Submitted: May 7, 2018
Results First Posted: August 9, 2018
Last Update Posted: February 26, 2019