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A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease

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: NCT02167256
Recruitment Status : Completed
First Posted : June 19, 2014
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
Sponsor:
Collaborator:
Alzheimer's Therapeutic Research Institute
Information provided by (Responsible Party):
Stephen M. Strittmatter, Yale University

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: AZD0530 100mg daily
Drug: AZD0530 125mg daily
Drug: Placebo
Enrollment 159
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Period Title: Overall Study
Started 79 80
Completed 58 70
Not Completed 21 10
Reason Not Completed
Adverse Event             13             6
Withdrawal by Subject             4             4
non-compliance             3             0
Study partner unable to participate             1             0
Arm/Group Title AZD0530 100mg Daily AZD0530 Placebo Total
Hide Arm/Group Description

Patients in the experimental group (50%) will be started on this dose. After 2 weeks, patients with a plasma drug level of <100ng/ml will receive 125mg AZD0530 daily and remain in the same experimental group as patient receiving 100mg daily.

AZD0530 100mg daily: All patients in experimental group (50%) will be started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily will receive 125mg daily of AZD0530.

50% of patients will receive placebo treatment for the duration of the study,

Placebo: 50% of patients will receive placebo treatment for the duration of the study.

Total of all reporting groups
Overall Number of Baseline Participants 79 80 159
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
  29.1%
17
  21.3%
40
  25.2%
>=65 years
56
  70.9%
63
  78.8%
119
  74.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
Female
41
  51.9%
31
  38.8%
72
  45.3%
Male
38
  48.1%
49
  61.3%
87
  54.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
White (not Hispanic)
74
  93.7%
68
  85.0%
142
  89.3%
Black or African American
4
   5.1%
3
   3.8%
7
   4.4%
Hispanic or Latino
1
   1.3%
6
   7.5%
7
   4.4%
American Indian or Alaskan Native
0
   0.0%
1
   1.3%
1
   0.6%
More than one race
0
   0.0%
1
   1.3%
1
   0.6%
Unknown or Not Reported
0
   0.0%
1
   1.3%
1
   0.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
Canada 3 4 7
United States 76 76 152
1.Primary Outcome
Title Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
Hide Description Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants is lower than total randomized participants due to a modified intent-to-treat analysis where only randomized participants who also underwent a post-baseline F18-FDG PET brain scan are included.
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 59 72
Mean (Standard Deviation)
Unit of Measure: umol/100g/min (change)
-0.06  (0.03) -0.05  (0.03)
2.Primary Outcome
Title Number of Participants With One or More Serious/Other Adverse Events Subjects With Mild AD as Assessed by Analysis of Adverse Events, Including Symptoms, and Abnormal Findings on Physical and Neurological Examinations, and Standard Labs.
Hide Description Assessment of any adverse effects between drug and placebo-treated subjects
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 79 80
Measure Type: Count of Participants
Unit of Measure: Participants
Subjects with one or more adverse events
73
  92.4%
68
  85.0%
Subjects with one or more serious adverse events
12
  15.2%
7
   8.8%
3.Secondary Outcome
Title The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function
Hide Description

The change in cognitive function between baseline and 12 months will be measured by the following tests:

  1. Alzheimer Disease Assessment Scale - Cognitive 11 (ADAS-cog11). Measures: Cognitive function Maximum score: 70; Minimum score: 0. Higher score equals worse cognitive function
  2. Mini-Mental State Examination (MMSE) Measures: Cognitive Function Maximum score: 30; Minimum score: 0. Higher score equal better cognitive function
  3. Alzheimer Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Measures: Ability to perform routine daily activities Maximum score: 78; Minimum score: 0. Higher score equals better ability to perform activities of daily living
  4. Clinical Dementia Rating Sum of Boxes (CDR-SO) Measures: Dementia severity Maximum score: 18; Minimum score: 0. Higher score equals more severe dementia.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 79 80
Mean (Standard Error)
Unit of Measure: Scores on a scale
ADAS-Cog score 7.26  (0.954) 6.14  (0.903)
MMSE score -3.84  (0.575) -3.33  (0.543)
ADCS-ADL -9.49  (1.263) -7.64  (1.199)
CDR-SO 1.946  (0.292) 1.468  (0.274)
4.Secondary Outcome
Title Percent Change in Brain Volume Before and After Treatment
Hide Description Change in volume of pre-defined brain regions between baseline and 12 months of treatment.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 57 62
Mean (Standard Error)
Unit of Measure: % change in volume
Entorhinal volume change -2.3939  (1.8138) -3.1002  (1.7446)
Whole brain volume change -1.5993  (1.0569) -1.7077  (1.0922)
Hippocampus volume change -0.8931  (1.8089) -1.542  (1.9893)
5.Secondary Outcome
Title Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42)
Hide Description Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants is lower than total randomized participants due to a modified intent-to-treat analysis where only randomized participants who also underwent a post-baseline cerebrospinal fluid analysis were included.
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 17 17
Mean (Standard Deviation)
Unit of Measure: pg/ml
CSF Total tau 91.7448  (212.7244) 1.2091  (131.2533)
CSF p-Tau 1.5837  (17.7504) -1.9986  (13.7311)
CSF Abeta 1-42 -1.3383  (47.3549) -1.3758  (43.3233)
6.Secondary Outcome
Title Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
Hide Description The results from the primary outcome with brain FDG-PET imaging was analyzed by ApoE genotype. Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants is lower than total randomized participants due to a modified intent-to-treat analysis where only randomized participants who also underwent a post-baseline F18-FDG PET brain scan are included.
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description:

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Number of Participants Analyzed 59 72
Mean (Standard Deviation)
Unit of Measure: umol/100g/min (change)
APOE4 carrier FDG-PET measure from baseline Number Analyzed 37 participants 47 participants
-0.06  (0.03) -0.05  (0.03)
APOE4 non-carrier FDG-PET measure from baseline Number Analyzed 22 participants 25 participants
-0.06  (0.03) -0.05  (0.03)
Time Frame Adverse events data were collected over a period of 1 year (study duration)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD0530 100mg/125mg Daily AZD0530 Placebo
Hide Arm/Group Description

AZD0530 100mg daily: All patients in experimental group (50%) were started on 100mg AZD0530 daily

AZD0530 125mg daily: Patients with plasma drug level <100ng/ml after 2 weeks of 100mg AZD0530 daily received 125mg daily of AZD0530.

Placebo: 50% of patients will receive placebo treatment for the duration of the study.
All-Cause Mortality
AZD0530 100mg/125mg Daily AZD0530 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/79 (1.27%)   0/80 (0.00%) 
Hide Serious Adverse Events
AZD0530 100mg/125mg Daily AZD0530 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   12/79 (15.19%)   7/80 (8.75%) 
Blood and lymphatic system disorders     
Blood and lymphatic system disorders   1/79 (1.27%)  0/80 (0.00%) 
Cardiac disorders     
Cardiac disorders   2/79 (2.53%)  1/80 (1.25%) 
Gastrointestinal disorders     
Gastrointestinal disorders   1/79 (1.27%)  1/80 (1.25%) 
Infections and infestations     
Infections and infestations   4/79 (5.06%)  0/80 (0.00%) 
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications   2/79 (2.53%)  1/80 (1.25%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders   0/79 (0.00%)  1/80 (1.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   0/79 (0.00%)  2/80 (2.50%) 
Nervous system disorders     
Nervous system disorders   1/79 (1.27%)  0/80 (0.00%) 
Psychiatric disorders     
Psychiatric disorders   2/79 (2.53%)  1/80 (1.25%) 
Reproductive system and breast disorders     
Reproductive system and breast disorders   1/79 (1.27%)  0/80 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
AZD0530 100mg/125mg Daily AZD0530 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   73/79 (92.41%)   65/80 (81.25%) 
Blood and lymphatic system disorders     
Blood and lymphatic system disorders   4/79 (5.06%)  2/80 (2.50%) 
Cardiac disorders     
Cardiac disorders   3/79 (3.80%)  6/80 (7.50%) 
Ear and labyrinth disorders     
Ear and labyrinth disorders   3/79 (3.80%)  1/80 (1.25%) 
Endocrine disorders     
Endocrine disorders   1/79 (1.27%)  0/80 (0.00%) 
Eye disorders     
Eye disorders   5/79 (6.33%)  1/80 (1.25%) 
Gastrointestinal disorders     
Gastrointestinal disorders   38/79 (48.10%)  23/80 (28.75%) 
General disorders     
General disorders and administration site conditions   15/79 (18.99%)  9/80 (11.25%) 
Immune system disorders     
Immune system disorders   2/79 (2.53%)  1/80 (1.25%) 
Infections and infestations     
Infections and infestations   28/79 (35.44%)  24/80 (30.00%) 
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications   13/79 (16.46%)  22/80 (27.50%) 
Investigations     
Investigations   24/79 (30.38%)  17/80 (21.25%) 
Metabolism and nutrition disorders     
Metabolism and nutrition disorders   11/79 (13.92%)  3/80 (3.75%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders   14/79 (17.72%)  24/80 (30.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   3/79 (3.80%)  8/80 (10.00%) 
Nervous system disorders     
Nervous system disorders   18/79 (22.78%)  16/80 (20.00%) 
Psychiatric disorders     
Psychiatric disorders   27/79 (34.18%)  17/80 (21.25%) 
Renal and urinary disorders     
Renal and urinary disorders   6/79 (7.59%)  2/80 (2.50%) 
Reproductive system and breast disorders     
Reproductive system and breast disorders   3/79 (3.80%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory, thoracic and mediastinal disorders   13/79 (16.46%)  7/80 (8.75%) 
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders   18/79 (22.78%)  10/80 (12.50%) 
Vascular disorders     
Vascular disorders   3/79 (3.80%)  6/80 (7.50%) 
Indicates events were collected by 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: Stephen Strittmatter
Organization: Yale University
Phone: 2037854878
EMail: stephen.strittmatter@yale.edu
Layout table for additonal information
Responsible Party: Stephen M. Strittmatter, Yale University
ClinicalTrials.gov Identifier: NCT02167256    
Other Study ID Numbers: 1404013830
4UH3TR000967-02 ( U.S. NIH Grant/Contract )
First Submitted: June 12, 2014
First Posted: June 19, 2014
Results First Submitted: June 19, 2019
Results First Posted: August 14, 2019
Last Update Posted: August 14, 2019