Trial Outcomes & Findings for Observational Study of Cognitive Outcomes for Subjects Who Have Had Prior PET Amyloid Imaging With Florbetapir F 18 (18F-AV-45) (NCT NCT00857506)

NCT ID: NCT00857506

Last Updated: 2013-03-28

Results Overview

The primary analysis was the comparison in the magnitude of change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) between Aβ+ and Aβ- subjects in the Mild Cognitive Impairment (MCI) population at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (last observation carried forward \[LOCF\]). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

152 participants

Primary outcome timeframe

Baseline and 36 months

Results posted on

2013-03-28

Participant Flow

All subjects were recruited from participants in study 18F-AV-45-A05 (NCT00702143)

Participant milestones

Participant milestones
Measure	Alzheimer's Disease Subject's with Alzheimer's Disease were recruited from study 18F-AV-45-A05 (NCT00702143). None of these subjects received additional interventions in study 18F-AV-45-A11.	Mild Cognitive Impairment Subject's with Mild Cognitive Impairment (MCI) were recruited from study 18F-AV-45-A05 (NCT00702143). 36 of these subjects received a single dose of florbetapir F 18 370 MBq (10 mCi), IV injection at the 24 month time point of study 18F-AV-45-A11 and comprise the safety set discussed in the Adverse Events section.	Cognitively Normal Cognitively Normal (CN) subjects were recruited from study 18F-AV-45-A05 (NCT00702143). 50 of these subjects received a single dose of florbetapir F 18 370 MBq (10 mCi), IV injection at the 24 month time point of study 18F-AV-45-A11 and comprise the safety set discussed in the Adverse Events section.
Overall Study STARTED	31	52	69
Overall Study COMPLETED	16	37	51
Overall Study NOT COMPLETED	15	15	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Observational Study of Cognitive Outcomes for Subjects Who Have Had Prior PET Amyloid Imaging With Florbetapir F 18 (18F-AV-45)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alzheimer's Disease n=31 Participants	Mild Cognitive Impairment n=52 Participants	Cognitively Normal n=69 Participants	Total n=152 Participants Total of all reporting groups
Age Continuous	76.7 years STANDARD_DEVIATION 9.23 • n=5 Participants	71.5 years STANDARD_DEVIATION 10.09 • n=7 Participants	69.8 years STANDARD_DEVIATION 11.26 • n=5 Participants	71.8 years STANDARD_DEVIATION 10.73 • n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	29 Participants n=7 Participants	41 Participants n=5 Participants	83 Participants n=4 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	23 Participants n=7 Participants	28 Participants n=5 Participants	69 Participants n=4 Participants
Region of Enrollment United States	31 participants n=5 Participants	52 participants n=7 Participants	69 participants n=5 Participants	152 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 36 months

Population: Brain amyloid status was determined by baseline florbetapir F 18 PET scans performed in study 18F-AV-45-A05 (NCT00702143).

The primary analysis was the comparison in the magnitude of change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) between Aβ+ and Aβ- subjects in the Mild Cognitive Impairment (MCI) population at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (last observation carried forward \[LOCF\]). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=17 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=30 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.
Change in ADAS-Cog for MCI Subjects	5.664 Scores on a scale Standard Error 1.4667	-0.710 Scores on a scale Standard Error 1.0905	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 36 months

Population: Brain amyloid status was determined by baseline florbetapir F 18 PET scans performed in study 18F-AV-45-A05 (NCT00702143).

The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the MCI population with clinically significant deterioration in ADAS-Cog (≥4) and Clinical Dementia Rating (CDR) global score (≥0.5) and conversion in diagnosis from MCI at baseline to AD or Cognitively Normal (CN) at 36 months. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=17 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=30 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.
Cognitive Decline in MCI Subjects ADAS-Cog Deterioration ≥4	8 Participants	3 Participants	—	—	—	—
Cognitive Decline in MCI Subjects CDR Deterioration ≥0.5	5 Participants	4 Participants	—	—	—	—
Cognitive Decline in MCI Subjects Conversion to AD	6 Participants	3 Participants	—	—	—	—
Cognitive Decline in MCI Subjects Conversion to CN	1 Participants	5 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 36 months

Population: Brain amyloid status was determined by baseline florbetapir F 18 PET scans performed in study 18F-AV-45-A05 (NCT00702143).

This analysis compared the magnitude of change from baseline in ADAS cognitive subscale (ADAS-Cog) scores between Aβ+ and Aβ- subjects in the CN and AD populations at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=10 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=57 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects n=19 Participants AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects n=9 Participants AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.
Change in ADAS-Cog in CN and AD Subjects	3.237 Scores on a scale Standard Error 0.9043	-0.094 Scores on a scale Standard Error 0.3679	8.879 Scores on a scale Standard Error 2.8812	3.811 Scores on a scale Standard Error 4.4261	—	—

SECONDARY outcome

Timeframe: Baseline and 36 months

Population: Brain amyloid status was determined by baseline florbetapir F 18 PET scans performed in study 18F-AV-45-A05 (NCT00702143).

The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the CN and AD populations with clinically significant deterioration in ADAS-Cog (≥4) and CDR global score (≥0.5). ADAS-Cog scores (range 0-70) indicate performance on a series of cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=10 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=57 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects n=19 Participants AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects n=9 Participants AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.
Cognitive Decline in CN and AD Subjects ADAS-Cog Deterioration ≥4	4 Participants	3 Participants	14 Participants	3 Participants	—	—
Cognitive Decline in CN and AD Subjects CDR Deterioration ≥0.5	4 Participants	5 Participants	12 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and 36 months

Population: Brain amyloid status was determined by baseline florbetapir F 18 PET scans performed in study 18F-AV-45-A05 (NCT00702143).

Change from baseline by diagnostic group in covariate-adjusted psychometric assessment scores at month 36 (LOCF). Assessments included Digit Symbol Substitution (DSS), Clinical Dementia Rating Sum of Boxes (CDR-SOB), Mini-Mental State Examination (MMSE), Wechsler Logical Memory Scale (WLMS) delayed and immediate recall, Category Verbal Fluency (CVF) animals and vegetables, Alzheimer's Disease Clinical Studies Consortium Activities of Daily Living (ADCS ADL) and Geriatric Depression Scale (GDS). The ranges for these scales are as follows: DSS (0-93), CDR-SOB (0-18), MMSE (0-30), WLMS delayed and immediate recall (0-25), CVF animals and vegetables (0-total number of relevant items named in 60 seconds), ADCS ADL (0-78) and GDS (0-15). For all scales except CDR-SOB and GDS a higher score indicates greater cognitive function. For CDR-SOB and GDS a higher score indicates increased dementia or depression, respectively.

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=10 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=57 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects n=17 Participants AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects n=30 Participants AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects n=19 Participants AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects n=9 Participants AD subjects with a negative florbetapir F 18 PET scan at baseline.
Covariate Adjusted Psychometric Score Change WLMS delayed recall	-0.429 Scores on a scale Standard Error 1.1278	0.970 Scores on a scale Standard Error 0.4504	-1.459 Scores on a scale Standard Error 1.1250	0.493 Scores on a scale Standard Error 0.8386	-0.179 Scores on a scale Standard Error 0.6722	1.490 Scores on a scale Standard Error 1.10058
Covariate Adjusted Psychometric Score Change WLMS immediate recall	-0.926 Scores on a scale Standard Error 1.0560	0.934 Scores on a scale Standard Error 0.4211	-1.875 Scores on a scale Standard Error 0.9949	0.496 Scores on a scale Standard Error 0.7405	-0.891 Scores on a scale Standard Error 0.8151	-0.231 Scores on a scale Standard Error 1.2620
Covariate Adjusted Psychometric Score Change GDS	-0.164 Scores on a scale Standard Error 0.4780	-0.182 Scores on a scale Standard Error 0.1926	0.066 Scores on a scale Standard Error 0.4753	-0.171 Scores on a scale Standard Error 0.3546	0.530 Scores on a scale Standard Error 0.5679	-0.727 Scores on a scale Standard Error 0.8264
Covariate Adjusted Psychometric Score Change DSS	-6.521 Scores on a scale Standard Error 2.9117	0.214 Scores on a scale Standard Error 1.1709	-10.940 Scores on a scale Standard Error 2.1569	0.133 Scores on a scale Standard Error 1.6082	-5.995 Scores on a scale Standard Error 2.2381	-0.011 Scores on a scale Standard Error 3.3534
Covariate Adjusted Psychometric Score Change CDR-SOB	0.765 Scores on a scale Standard Error 0.1520	0.097 Scores on a scale Standard Error 0.0632	1.985 Scores on a scale Standard Error 0.5321	0.392 Scores on a scale Standard Error 0.3976	4.048 Scores on a scale Standard Error 0.8008	0.121 Scores on a scale Standard Error 1.1739
Covariate Adjusted Psychometric Score Change MMSE	-0.740 Scores on a scale Standard Error 0.3282	-0.396 Scores on a scale Standard Error 0.1329	-2.882 Scores on a scale Standard Error 0.8053	-0.300 Scores on a scale Standard Error 0.6023	-3.924 Scores on a scale Standard Error 1.2418	1.173 Scores on a scale Standard Error 1.8299
Covariate Adjusted Psychometric Score Change CVF animals	-2.785 Scores on a scale Standard Error 1.5735	-0.617 Scores on a scale Standard Error 0.6383	-3.177 Scores on a scale Standard Error 1.0980	-0.533 Scores on a scale Standard Error 0.8213	-4.772 Scores on a scale Standard Error 0.8096	0.085 Scores on a scale Standard Error 1.2654
Covariate Adjusted Psychometric Score Change CVF vegetables	-2.087 Scores on a scale Standard Error 1.0202	0.156 Scores on a scale Standard Error 0.4150	-2.278 Scores on a scale Standard Error 0.8162	0.757 Scores on a scale Standard Error 0.6109	-3.051 Scores on a scale Standard Error 0.7022	0.621 Scores on a scale Standard Error 1.0959
Covariate Adjusted Psychometric Score Change ADCS ADL	-0.629 Scores on a scale Standard Error 0.7272	-0.191 Scores on a scale Standard Error 0.2796	-4.932 Scores on a scale Standard Error 2.2040	-2.839 Scores on a scale Standard Error 1.6288	-20.789 Scores on a scale Standard Error 4.5189	-5.668 Scores on a scale Standard Error 6.6271

SECONDARY outcome

Timeframe: Baseline and 36 months

Correlation between change from baseline to 36 month ADAS-Cog score and baseline global average SUVR by diagnostic group is provided below. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance. Standard Uptake Value Ratio (SUVR) is the ratio of tracer uptake in the cortex and cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the cortex as compared to the cerebellum whereas scores less than 1 indicate the opposite.

Outcome measures

Outcome measures
Measure	Amyloid-Beta Positive MCI Subjects n=28 Participants MCI subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative MCI Subjects n=47 Participants MCI subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects n=67 Participants AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.	Amyloid-Beta Positive AD Subjects AD subjects with a positive florbetapir F 18 PET scan at baseline.	Amyloid-Beta Negative AD Subjects AD subjects with a negative florbetapir F 18 PET scan at baseline.
Correlation of Change in ADAS-Cog and SUVR	0.364 Pearson Correlation Coefficient	0.502 Pearson Correlation Coefficient	0.308 Pearson Correlation Coefficient	—	—	—

Adverse Events

Alzheimer's Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Mild Cognitive Impairment

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Cognitively Normal

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alzheimer's Disease	Mild Cognitive Impairment n=36 participants at risk	Cognitively Normal n=50 participants at risk
Respiratory, thoracic and mediastinal disorders Influenza	— 0/0 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	2.8% 1/36 • Number of events 1 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	0.00% 0/50 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.

Other adverse events

Other adverse events
Measure	Alzheimer's Disease	Mild Cognitive Impairment n=36 participants at risk	Cognitively Normal n=50 participants at risk
Gastrointestinal disorders Nausea	— 0/0 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	2.8% 1/36 • Number of events 1 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	0.00% 0/50 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.
Nervous system disorders Headache	— 0/0 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	0.00% 0/36 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.	2.0% 1/50 • Number of events 1 The number of subjects at risk was determined by the number of subjects who received an injection of florbetapir F 18 at the 24 month time point of study 18F-AV-45-A11. As indicated in the participant flow group description, there were 36 MCI and 50 CN subjects who qualified for inclusion in the safety set.

Additional Information

Chief Medical Officer

Avid Radiopharmaceuticals, Inc.

Phone: 215-298-0700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60