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Feasibility Study in Subjects With Mild to Moderate Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT02560753
Recruitment Status : Completed
First Posted : September 25, 2015
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
T3D Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Intervention Drug: T3D-959
Enrollment 36
Recruitment Details  
Pre-assignment Details  
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Period Title: Overall Study
Started 9 9 10 8
Completed 8 9 9 8
Not Completed 1 0 1 0
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg Total
Hide Arm/Group Description

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Total of all reporting groups
Overall Number of Baseline Participants 9 9 10 8 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 10 participants 8 participants 36 participants
<=65 years
2
  22.2%
2
  22.2%
3
  30.0%
1
  12.5%
8
  22.2%
65-74 years
2
  22.2%
4
  44.4%
2
  20.0%
2
  25.0%
10
  27.8%
75-84 years
3
  33.3%
3
  33.3%
1
  10.0%
5
  62.5%
12
  33.3%
>84 years
2
  22.2%
0
   0.0%
4
  40.0%
0
   0.0%
6
  16.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 10 participants 8 participants 36 participants
Female
5
  55.6%
5
  55.6%
6
  60.0%
4
  50.0%
20
  55.6%
Male
4
  44.4%
4
  44.4%
4
  40.0%
4
  50.0%
16
  44.4%
ApoE4 genotype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 9 participants 8 participants 34 participants
ApoE4 positive
4
  50.0%
2
  22.2%
4
  44.4%
3
  37.5%
13
  38.2%
ApoE4 negative
4
  50.0%
7
  77.8%
5
  55.6%
5
  62.5%
21
  61.8%
[1]
Measure Analysis Population Description: This measure is assessed on study completers
1.Primary Outcome
Title Change From Baseline (End of Treatment - Baseline) for FDG-PET Imaging With Whole Brain and White Matter as Reference Region
Hide Description Changes in relative brain glucose metabolism (delta R CMRgl) were measured by FDG-PET. At each time point, a ratio of the PET reading in a pre-defined region of interest (sROI), known to be affected by AD, and in a reference region (RR) that is spared in AD, is determined. This ratio is defined as "sROI index" (spared region). A second RR, brain white matter (WM), was also used in this calculation: sROI index" (WM) value. delta sROI is defined as change in the sROI index values, over the treatment period. In this study we are looking for changes in delta sROI with increasing doses of T3D-959. Dose dependent changes in delta sROI (AD spared) are compared to those observed with the WM as the RR: delta sROI (WM). Dose related changes in delta sROI suggests T3D-959 is entering the brain and effecting glucose metabolism in a dose dependent fashion.
Time Frame after 14 days of treatment
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Hide Analysis Population Description
Both + & - values for delta sROI represent "better outcomes" with regard to the demonstrating pharmacological activity of a PPAR delta, such as T3D-959, in the brain. It is unknown at this time, both from this presented data and from the literature, whether the pharmacological action of a PPAR delta agonist will translate to better outcomes in AD.
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description:

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Overall Number of Participants Analyzed 9 9 10 8
Mean (Standard Deviation)
Unit of Measure: ratio
delta sROI (AD spared) 0.0015  (0.02057) 0.0034  (0.01671) -0.0204  (0.01952) -0.0293  (0.01744)
delta sROI (white matter) 0.0016  (0.04008) 0.0053  (0.02471) -0.0200  (0.01979) -0.0355  (0.02303)
2.Primary Outcome
Title The Effect of Treatment With T3D-959 on Changes in Resting State Blood Oxygen Level Dependent (BOLD) Signal in Functional Magnetic Resonance Imaging (fMRI) of the Brain Areas Associated With Cognitive Tasks.
Hide Description Changes in BOLD fMRI parameters such as GoF (see Study Description) over the course of two weeks of treatment, were obtained in this study. BOLD fMRI has been used in cross sectional and longitudinal studies of Alzheimer's subjects, for instance in the Alzheimer's Disease Neuroimaging Initiative studies. However, no studies monitoring Default Mode Networks measured parameters such as GoF, in the context of an effective AD therapeutic, as a result it is difficult to interpret the observed small changes listed in BOLD fMRI parameters obtained in this trial. Instead the changes in the listed BOLD fMRI parameters (EOT - BL) are reported without interpretation. These values represent changes in fMRI connectivity patterns over time and are unitless.
Time Frame after 14 days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description:

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Overall Number of Participants Analyzed 8 9 9 8
Mean (Standard Deviation)
Unit of Measure: unitless
GoF (Goodness of Fit) 0.0129  (0.08528) -0.0120  (0.0646) 0.0118  (0.03375) 0.0076  (0.08755)
Hippo-PreC Link (Hippocampus - Precuneus Link) -0.1213  (0.17904) 0.1320  (0.22964) 0.1196  (0.23035) -0.0349  (0.18496)
GlobEff_DMN(Global Efficiency from DMN Regions) 0.0033  (0.00734) -0.0036  (0.00940) -0.0004  (0.00926) -0.0001  (0.00397)
GlobEff_AAL(Global Efficiency from AAL Regions) -0.0001  (0.00664) -0.0006  (0.00972) -0.0031  (0.01060) -0.0005  (0.00517)
ALFF_lPCC_PreC (Amplitude of Low Frequency Fluctua -0.0578  (0.12314) -0.0190  (0.11983) -0.0505  (0.07463) -0.0206  (0.10508)
ALFF_rPCC_PreC (ALFF from right PCC and precuneus) -0.0752  (0.09059) -0.0127  (0.12127) -0.0097  (0.08362) -0.0325  (0.11092)
fALFF_lPCC_PreC (Ratio ALFF from left PCC & prec 0.0121  (0.03246) 0.0068  (0.03510) -0.0132  (0.03955) -0.0167  (0.03284)
fALFF_rPCC_PreC (Ratio ALFF from right PCC & pre -0.0080  (0.04094) 0.0084  (0.04325) -0.0007  (0.03913) -0.0118  (0.04236)
ReHo_lPCC_PreC (Regional Homogeneity in left PCC a -0.0665  (0.18502) 0.0237  (0.14028) -0.0369  (0.09702) 0.0194  (0.20061)
ReHo_rPCC_PreC (Regional Homogeneity in right PCC -0.0390  (0.06406) -0.0663  (0.22082) -0.0895  (0.10541) -0.0041  (0.15836)
ALFF_lIPL (ALFF from left inferior parietal lobule -0.0635  (0.09445) 0.0104  (0.05763) -0.0102  (0.12016) -0.0401  (0.05657)
ALFF_rIPL(ALFF from right IPL) -0.0493  (0.11288) -0.0276  (0.12720) 0.0346  (0.09654) -0.1089  (0.13935)
fALFF_lIPL (Ratio ALFF from left IPL) -0.0296  (0.03988) 0.0164  (0.02269) -0.0107  (0.06563) -0.0350  (0.04570)
fALFF_rIPL (Ratio ALFF from right IPL) -0.0342  (0.03912) 0.0061  (0.03286) 0.0023  (0.02771) -0.0395  (0.05327)
ReHo_lIPL (Regional Homogeneity in left IPL) -0.0694  (0.15420) 0.0147  (0.14620) -0.0249  (0.19178) -0.0062  (0.06575)
ReHo_rIPL (Regional Homogeneity in right IPL) -0.0694  (0.15420) 0.0147  (0.14620) -0.0249  (0.19178) -0.0062  (0.06575)
3.Secondary Outcome
Title Change From Baseline in the Score of the Digit Symbol Substitution Test
Hide Description The digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment. Scores on the DSST range from 0-93.
Time Frame after 14 days of treatment
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Hide Analysis Population Description
3 mg group:A subject Dc'd prior to the EOT & another subject became uncooperative at EOT and refused to take the DSST. Her results for EOT were missing. 30 mg: A subject DC'd prior to EOT, another subject was described as being very agitated at the EOT. The results presented omitted this subject's EOT data.
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description:

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Overall Number of Participants Analyzed 9 9 10 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change from baseline at end of treatment (day 14) Number Analyzed 7 participants 9 participants 8 participants 8 participants
4.429  (9.1626) 1.000  (5.500) 0.750  (3.6154) 1.125  (4.5493)
Change from baseline at follow-up (day 21) Number Analyzed 8 participants 9 participants 9 participants 8 participants
5.375  (8.5011) 3.111  (5.0111) 4.000  (5.6789) 6.625  (11.4385)
4.Secondary Outcome
Title Change From Baseline in the Total Score of the 11-item Alzheimer's Disease Assessment Scale - Cognitive Subscale
Hide Description The 11-item Alzheimer's Disease Assessment Scale (ADAS-Cog 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. The score can range between 0 and 70. A higher score indicates more cognitive impairment. A positive change in the score indicates cognitive worsening. The minimum severity score is 0 and the maximum severity score is 70.
Time Frame after 14 days of treatment
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Hide Analysis Population Description
3 mg group:A subject Dc'd prior to the EOT & another subject became uncooperative at EOT and refused to take the DSST. Her results for EOT were missing. 30 mg: A subject DC'd prior to EOT, another subject was described as being very agitated at the EOT. The results presented omitted this subject's EOT data.
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description:

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Overall Number of Participants Analyzed 9 9 10 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change from baseline at end of treatment (day 14) Number Analyzed 8 participants 9 participants 8 participants 8 participants
-2.367  (4.0417) -0.552  (3.1467) -2.709  (3.9801) 1.970  (5.2191)
Change from baseline at follow-up (day 21) Number Analyzed 8 participants 9 participants 9 participants 8 participants
-3.409  (3.5168) -0.624  (3.8134) -4.119  (3.8163) 2.795  (4.1567)
5.Other Pre-specified Outcome
Title Safety and Tolerability of Treatment With T3D-959 Over a 2-week Period in Subjects With Mild-to-moderate AD. New
Hide Description Number of participants with treatment related adverse events (AEs) as assessed by analysis of adverse events, including symptoms, and abnormal findings on physical and neurological examinations, and standard labs.
Time Frame after 14 days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
3 mg group:A subject Dc'd prior to the EOT & another subject became uncooperative at EOT and refused to take the DSST. Her results for EOT were missing. 30 mg: A subject DC'd prior to EOT, another subject was described as being very agitated at the EOT. The results presented omitted this subject's EOT data.
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description:

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

Overall Number of Participants Analyzed 9 9 10 8
Measure Type: Number
Unit of Measure: participants
Subjects with at Least One Serious Adverse Events 0 0 0 0
Subjects with at Least One Drug-related AE 0 0 1 0
Subjects with at Least One mild AE 2 0 1 0
Subjects with at Least One moderate AE 1 0 2 0
Subjects with at Least One serious AE 0 0 0 0
Time Frame pre treatment, during the two weeks of treatment and on follow-up one week after treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Hide Arm/Group Description

subjects took 3mg by mouth once daily for two weeks, with or without food.

T3D-959: The 3mg dosage was supplied as 1mg capsules (three capsules, taken once daily by mouth)

subjects took 10mg by mouth once daily for two weeks, with or without food.

The 10mg dosage was supplied as 5mg capsules (two capsules, taken once daily by mouth)

subjects took 30mg by mouth once daily for two weeks, with or without food.

The 30mg dosage was supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth)

subjects took 90mg by mouth once daily for two weeks, with or without food.

The 90mg dosage was supplied as 15mg capsules (six capsules, taken once daily by mouth)

All-Cause Mortality
T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)      0/9 (0.00%)      0/10 (0.00%)      0/8 (0.00%)    
Hide Serious Adverse Events
T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/9 (0.00%)      0/10 (0.00%)      0/8 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
T3D-959 3mg T3D-959 10mg T3D-959 30mg T3D-959 90mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/9 (11.11%)      0/9 (0.00%)      1/10 (10.00%)      0/8 (0.00%)    
Musculoskeletal and connective tissue disorders         
Muscular Weakness * 1  0/9 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1 0/8 (0.00%)  0
Tendonitis * 1  1/9 (11.11%)  1 0/9 (0.00%)  0 0/10 (0.00%)  0 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA
*
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: John Didsbury, PhD
Organization: T3DTherapeutics
Phone: 9199490517
EMail: didsj919@t3dtherapeutics.com
Layout table for additonal information
Responsible Party: T3D Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02560753    
Other Study ID Numbers: T3D959-201
First Submitted: July 28, 2015
First Posted: September 25, 2015
Results First Submitted: March 6, 2018
Results First Posted: July 30, 2018
Last Update Posted: July 30, 2018