Trial Outcomes & Findings for A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease (NCT NCT02167256)

Last Updated: 2019-08-14

Results Overview

Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

159 participants

Primary outcome timeframe

12 months

Results posted on

2019-08-14

Participant Flow

Participant milestones

Participant milestones
Measure	AZD0530 100mg/125mg Daily 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.	AZD0530 Placebo Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Study STARTED	79	80
Overall Study COMPLETED	58	70
Overall Study NOT COMPLETED	21	10

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD0530 100mg/125mg Daily 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.	AZD0530 Placebo Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Overall Study Adverse Event	13	6
Overall Study Withdrawal by Subject	4	4
Overall Study non-compliance	3	0
Overall Study Study partner unable to participate	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD0530 100mg Daily n=79 Participants 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.	AZD0530 Placebo n=80 Participants 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 n=159 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical >=65 years	56 Participants n=5 Participants	63 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	31 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	49 Participants n=7 Participants	87 Participants n=5 Participants
Race/Ethnicity, Customized White (not Hispanic)	74 Participants n=5 Participants	68 Participants n=7 Participants	142 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment United States	76 participants n=5 Participants	76 participants n=7 Participants	152 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: 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.

Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=59 Participants 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.	AZD0530 Placebo n=72 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging	-0.06 umol/100g/min (change) Standard Deviation 0.03	-0.05 umol/100g/min (change) Standard Deviation 0.03

PRIMARY outcome

Timeframe: 12 months

Assessment of any adverse effects between drug and placebo-treated subjects

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=79 Participants 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.	AZD0530 Placebo n=80 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
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. Subjects with one or more adverse events	73 Participants	68 Participants
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. Subjects with one or more serious adverse events	12 Participants	7 Participants

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=79 Participants 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.	AZD0530 Placebo n=80 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function ADAS-Cog score	7.26 Scores on a scale Standard Error 0.954	6.14 Scores on a scale Standard Error 0.903
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function MMSE score	-3.84 Scores on a scale Standard Error 0.575	-3.33 Scores on a scale Standard Error 0.543
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function ADCS-ADL	-9.49 Scores on a scale Standard Error 1.263	-7.64 Scores on a scale Standard Error 1.199
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function CDR-SO	1.946 Scores on a scale Standard Error 0.292	1.468 Scores on a scale Standard Error 0.274

SECONDARY outcome

Timeframe: 12 months

Change in volume of pre-defined brain regions between baseline and 12 months of treatment.

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=57 Participants 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.	AZD0530 Placebo n=62 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Percent Change in Brain Volume Before and After Treatment Entorhinal volume change	-2.3939 % change in volume Standard Error 1.8138	-3.1002 % change in volume Standard Error 1.7446
Percent Change in Brain Volume Before and After Treatment Whole brain volume change	-1.5993 % change in volume Standard Error 1.0569	-1.7077 % change in volume Standard Error 1.0922
Percent Change in Brain Volume Before and After Treatment Hippocampus volume change	-0.8931 % change in volume Standard Error 1.8089	-1.542 % change in volume Standard Error 1.9893

SECONDARY outcome

Timeframe: 12 months

Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=17 Participants 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.	AZD0530 Placebo n=17 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42) CSF Total tau	91.7448 pg/ml Standard Deviation 212.7244	1.2091 pg/ml Standard Deviation 131.2533
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42) CSF p-Tau	1.5837 pg/ml Standard Deviation 17.7504	-1.9986 pg/ml Standard Deviation 13.7311
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42) CSF Abeta 1-42	-1.3383 pg/ml Standard Deviation 47.3549	-1.3758 pg/ml Standard Deviation 43.3233

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	AZD0530 100mg/125mg Daily n=59 Participants 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.	AZD0530 Placebo n=72 Participants Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging APOE4 carrier FDG-PET measure from baseline	-0.06 umol/100g/min (change) Standard Deviation 0.03	-0.05 umol/100g/min (change) Standard Deviation 0.03
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging APOE4 non-carrier FDG-PET measure from baseline	-0.06 umol/100g/min (change) Standard Deviation 0.03	-0.05 umol/100g/min (change) Standard Deviation 0.03

Adverse Events

AZD0530 100mg/125mg Daily

Serious events: 12 serious events

Other events: 73 other events

Deaths: 1 deaths

AZD0530 Placebo

Serious events: 7 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD0530 100mg/125mg Daily n=79 participants at risk 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.	AZD0530 Placebo n=80 participants at risk Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Infections and infestations Infections and infestations	5.1% 4/79 • Adverse events data were collected over a period of 1 year (study duration)	0.00% 0/80 • Adverse events data were collected over a period of 1 year (study duration)
Cardiac disorders Cardiac disorders	2.5% 2/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	2.5% 2/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Psychiatric disorders Psychiatric disorders	2.5% 2/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Blood and lymphatic system disorders Blood and lymphatic system disorders	1.3% 1/79 • Adverse events data were collected over a period of 1 year (study duration)	0.00% 0/80 • Adverse events data were collected over a period of 1 year (study duration)
Nervous system disorders Nervous system disorders	1.3% 1/79 • Adverse events data were collected over a period of 1 year (study duration)	0.00% 0/80 • Adverse events data were collected over a period of 1 year (study duration)
Reproductive system and breast disorders Reproductive system and breast disorders	1.3% 1/79 • Adverse events data were collected over a period of 1 year (study duration)	0.00% 0/80 • Adverse events data were collected over a period of 1 year (study duration)
Gastrointestinal disorders Gastrointestinal disorders	1.3% 1/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.00% 0/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0.00% 0/79 • Adverse events data were collected over a period of 1 year (study duration)	2.5% 2/80 • Adverse events data were collected over a period of 1 year (study duration)

Other adverse events

Additional Information

Stephen Strittmatter

Yale University

Phone: 2037854878

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	AZD0530 100mg/125mg Daily n=79 participants at risk 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.	AZD0530 Placebo n=80 participants at risk Placebo: 50% of patients will receive placebo treatment for the duration of the study.
Gastrointestinal disorders Gastrointestinal disorders	48.1% 38/79 • Adverse events data were collected over a period of 1 year (study duration)	28.7% 23/80 • Adverse events data were collected over a period of 1 year (study duration)
Psychiatric disorders Psychiatric disorders	34.2% 27/79 • Adverse events data were collected over a period of 1 year (study duration)	21.2% 17/80 • Adverse events data were collected over a period of 1 year (study duration)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	22.8% 18/79 • Adverse events data were collected over a period of 1 year (study duration)	12.5% 10/80 • Adverse events data were collected over a period of 1 year (study duration)
Metabolism and nutrition disorders Metabolism and nutrition disorders	13.9% 11/79 • Adverse events data were collected over a period of 1 year (study duration)	3.8% 3/80 • Adverse events data were collected over a period of 1 year (study duration)
Investigations Investigations	30.4% 24/79 • Adverse events data were collected over a period of 1 year (study duration)	21.2% 17/80 • Adverse events data were collected over a period of 1 year (study duration)
General disorders General disorders and administration site conditions	19.0% 15/79 • Adverse events data were collected over a period of 1 year (study duration)	11.2% 9/80 • Adverse events data were collected over a period of 1 year (study duration)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	16.5% 13/79 • Adverse events data were collected over a period of 1 year (study duration)	8.8% 7/80 • Adverse events data were collected over a period of 1 year (study duration)
Infections and infestations Infections and infestations	35.4% 28/79 • Adverse events data were collected over a period of 1 year (study duration)	30.0% 24/80 • Adverse events data were collected over a period of 1 year (study duration)
Renal and urinary disorders Renal and urinary disorders	7.6% 6/79 • Adverse events data were collected over a period of 1 year (study duration)	2.5% 2/80 • Adverse events data were collected over a period of 1 year (study duration)
Eye disorders Eye disorders	6.3% 5/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Nervous system disorders Nervous system disorders	22.8% 18/79 • Adverse events data were collected over a period of 1 year (study duration)	20.0% 16/80 • Adverse events data were collected over a period of 1 year (study duration)
Blood and lymphatic system disorders Blood and lymphatic system disorders	5.1% 4/79 • Adverse events data were collected over a period of 1 year (study duration)	2.5% 2/80 • Adverse events data were collected over a period of 1 year (study duration)
Ear and labyrinth disorders Ear and labyrinth disorders	3.8% 3/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Reproductive system and breast disorders Reproductive system and breast disorders	3.8% 3/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Immune system disorders Immune system disorders	2.5% 2/79 • Adverse events data were collected over a period of 1 year (study duration)	1.2% 1/80 • Adverse events data were collected over a period of 1 year (study duration)
Endocrine disorders Endocrine disorders	1.3% 1/79 • Adverse events data were collected over a period of 1 year (study duration)	0.00% 0/80 • Adverse events data were collected over a period of 1 year (study duration)
Cardiac disorders Cardiac disorders	3.8% 3/79 • Adverse events data were collected over a period of 1 year (study duration)	7.5% 6/80 • Adverse events data were collected over a period of 1 year (study duration)
Vascular disorders Vascular disorders	3.8% 3/79 • Adverse events data were collected over a period of 1 year (study duration)	7.5% 6/80 • Adverse events data were collected over a period of 1 year (study duration)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	3.8% 3/79 • Adverse events data were collected over a period of 1 year (study duration)	10.0% 8/80 • Adverse events data were collected over a period of 1 year (study duration)
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	16.5% 13/79 • Adverse events data were collected over a period of 1 year (study duration)	27.5% 22/80 • Adverse events data were collected over a period of 1 year (study duration)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	17.7% 14/79 • Adverse events data were collected over a period of 1 year (study duration)	30.0% 24/80 • Adverse events data were collected over a period of 1 year (study duration)