Trial Outcomes & Findings for Florbetaben (BAY94-9172) PET (Positron Emission Tomography) Imaging in MCI (Mild Cognitive Impairment) Patients (NCT NCT01138111)
NCT ID: NCT01138111
Last Updated: 2014-06-25
Results Overview
Mean SUVRs were calculated for subjects who did and did not progress to Alzheimer's Disease (AD) during the study for each PET scan time point (baseline, 12 and 24 months)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
45 participants
Primary outcome timeframe
1 scanning period post injection to be evaluated at baseline, 12 months and 24 months
Results posted on
2014-06-25
Participant Flow
A total of 71 patients were screened at one study center in Australia. The first subject's consent was obtained on 02 JUN 2008.
26 subjects were screen failures and did not have study drug administered.
Participant milestones
| Measure |
MCI Subjects
Subjects with mild cognitive impairment (MCI) receiving florbetaben (BAY94-9172) : single intravenous injection of 300 megaBecqerels (MBq) florbetaben, at baseline, at 12 and 24 months
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
MCI Subjects
Subjects with mild cognitive impairment (MCI) receiving florbetaben (BAY94-9172) : single intravenous injection of 300 megaBecqerels (MBq) florbetaben, at baseline, at 12 and 24 months
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
Baseline Characteristics
Florbetaben (BAY94-9172) PET (Positron Emission Tomography) Imaging in MCI (Mild Cognitive Impairment) Patients
Baseline characteristics by cohort
| Measure |
MCI Subjects
n=45 Participants
Subjects with mild cognitive impairment (MCI) receiving florbetaben (BAY94-9172) : single intravenous injection 2 mL to 10 mL, at baseline, at 12 and 24 months
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
39 Participants
n=5 Participants
|
|
Age, Continuous
|
72.7 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
45 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 scanning period post injection to be evaluated at baseline, 12 months and 24 monthsPopulation: All subjects receiving study drug with PET scan data at the respective timepoint
Mean SUVRs were calculated for subjects who did and did not progress to Alzheimer's Disease (AD) during the study for each PET scan time point (baseline, 12 and 24 months)
Outcome measures
| Measure |
Not Progressed to AD (Baseline)
n=26 Participants
Mean SUVR for the baseline PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (Baseline)
n=19 Participants
Mean SUVR for the baseline PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (12 Month)
n=24 Participants
Mean SUVR for the 12 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (12 Month)
n=17 Participants
Mean SUVR for the 12 month PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (24 Month)
n=22 Participants
Mean SUVR for the 24 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (24 Month)
n=14 Participants
Mean SUVR for the 24 month PET scan in subjects who progressed to AD during the study
|
|---|---|---|---|---|---|---|
|
Quantitative Assessment of Neocortical SUVRs (Mean Standard Uptake Value Ratios) as a Measure of Florbetaben Uptake
|
1.430 SUVR
Standard Deviation 0.252
|
1.726 SUVR
Standard Deviation 0.227
|
1.442 SUVR
Standard Deviation 0.270
|
1.738 SUVR
Standard Deviation 0.236
|
1.439 SUVR
Standard Deviation 0.219
|
1.796 SUVR
Standard Deviation 0.296
|
SECONDARY outcome
Timeframe: 1 scanning period post injection to be evaluated at baseline, at 12 months and at 24 monthsPopulation: All subjects receiving study drug
This outcome measure showed the number of abnormal scans in subjects with MCI progressing to AD and those who did not progress compared to subjects with normal scans that did not progress and those who did progress.
Outcome measures
| Measure |
Not Progressed to AD (Baseline)
n=26 Participants
Mean SUVR for the baseline PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (Baseline)
n=19 Participants
Mean SUVR for the baseline PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (12 Month)
n=24 Participants
Mean SUVR for the 12 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (12 Month)
n=18 Participants
Mean SUVR for the 12 month PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (24 Month)
n=22 Participants
Mean SUVR for the 24 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (24 Month)
n=14 Participants
Mean SUVR for the 24 month PET scan in subjects who progressed to AD during the study
|
|---|---|---|---|---|---|---|
|
Number of Normal and Abnormal Scans in Patients With MCI Progressing to AD and Those Who do Not Progress Based on a Threshold of Neocortical SUVR=1.4
Number with Normal Scan
|
17 participants
|
2 participants
|
15 participants
|
2 participants
|
12 participants
|
1 participants
|
|
Number of Normal and Abnormal Scans in Patients With MCI Progressing to AD and Those Who do Not Progress Based on a Threshold of Neocortical SUVR=1.4
Number with Abnormal Scan
|
9 participants
|
17 participants
|
9 participants
|
16 participants
|
10 participants
|
13 participants
|
SECONDARY outcome
Timeframe: 2 scanning periods post injection to be evaluated each at baseline, at 12 months, and at 24 monthsPopulation: All subjects with PET data at the referenced study time point
At each study time point (baseline, 12 months and 24 months) PET images were obtained at 45 min and again at 90 post injection. These images were assigned a BAPL score of 1, 2 or 3 based on the reader's evaluation of the scan. A BAPL scores of 1 was considered normal, and scores of 2 and 3 were considered abnormal. These scores were compared to subjects clinical diagnosis for AD at the end of the study follow up period.
Outcome measures
| Measure |
Not Progressed to AD (Baseline)
n=26 Participants
Mean SUVR for the baseline PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (Baseline)
n=19 Participants
Mean SUVR for the baseline PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (12 Month)
n=24 Participants
Mean SUVR for the 12 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (12 Month)
n=17 Participants
Mean SUVR for the 12 month PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (24 Month)
n=22 Participants
Mean SUVR for the 24 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (24 Month)
n=14 Participants
Mean SUVR for the 24 month PET scan in subjects who progressed to AD during the study
|
|---|---|---|---|---|---|---|
|
Number and Proportion of Normal and Abnormal Scans Based on Brain ß-amyloid Plaque Load (BAPL) in Subjects With MCI Converting to AD and Those Who do Not Progress
45 min normal PET assessment
|
15 participants
|
2 participants
|
16 participants
|
0 participants
|
14 participants
|
0 participants
|
|
Number and Proportion of Normal and Abnormal Scans Based on Brain ß-amyloid Plaque Load (BAPL) in Subjects With MCI Converting to AD and Those Who do Not Progress
45 min abnormal PET assessment
|
11 participants
|
17 participants
|
8 participants
|
17 participants
|
8 participants
|
14 participants
|
|
Number and Proportion of Normal and Abnormal Scans Based on Brain ß-amyloid Plaque Load (BAPL) in Subjects With MCI Converting to AD and Those Who do Not Progress
90 min normal PET assessment
|
16 participants
|
0 participants
|
14 participants
|
1 participants
|
14 participants
|
2 participants
|
|
Number and Proportion of Normal and Abnormal Scans Based on Brain ß-amyloid Plaque Load (BAPL) in Subjects With MCI Converting to AD and Those Who do Not Progress
90 min abnormal PET assessment
|
10 participants
|
19 participants
|
10 participants
|
16 participants
|
8 participants
|
12 participants
|
SECONDARY outcome
Timeframe: 2 scanning periods post injection to be evaluated at baselinePopulation: All subjects with PET data at the referenced study time point
Sensitivity, specificity, NPV and PPV were measured based on subject BAPL scores by time point and imaging window, compared to clinical diagnosis of AD during the study period. A BAPL score of 1 was considered negative for the presence of beta-amyloid, and scores of 2 and 3 were considered positive. For this study, sensitivity was defined as the percentage of subjects with a clinical diagnosis of AD who also had a positive PET scan (BAPL score of 2 or 3) at the respective time point. Specificity was defined as the percentage of subjects with a clinical diagnosis of non-AD who also had a negative PET scan (BAPL score of 0 or 1) at the respective time point. PPV was defined as the probability that a subject with a positive PET scan would have a clinical diagnosis of AD sometime during the 2 year follow up period. NPV was defined as the probability that a subject with a negative PET scan would not have a clinical diagnosis of AD at any point during the 2 year follow up period.
Outcome measures
| Measure |
Not Progressed to AD (Baseline)
n=45 Participants
Mean SUVR for the baseline PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (Baseline)
n=45 Participants
Mean SUVR for the baseline PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (12 Month)
n=41 Participants
Mean SUVR for the 12 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (12 Month)
n=41 Participants
Mean SUVR for the 12 month PET scan in subjects who progressed to AD during the study
|
Not Progressed to AD (24 Month)
n=36 Participants
Mean SUVR for the 24 month PET scan in subjects who did not progress to AD during the study
|
Progressed to AD (24 Month)
n=36 Participants
Mean SUVR for the 24 month PET scan in subjects who progressed to AD during the study
|
|---|---|---|---|---|---|---|
|
Sensitivity/Specificity/Negative Predictive Value (NPV)/Positive Predictive Value (PPV) at Baseline, 12, and 24 Months in the Detection of Significant Brain ß-amyloid Plaque Load in Patients With MCI Progressing to AD Compared to Those Who do Not Progress
Sensitivity
|
89.47 percentage of subjects
|
100.00 percentage of subjects
|
100.00 percentage of subjects
|
94.12 percentage of subjects
|
100.00 percentage of subjects
|
85.71 percentage of subjects
|
|
Sensitivity/Specificity/Negative Predictive Value (NPV)/Positive Predictive Value (PPV) at Baseline, 12, and 24 Months in the Detection of Significant Brain ß-amyloid Plaque Load in Patients With MCI Progressing to AD Compared to Those Who do Not Progress
Specificity
|
57.69 percentage of subjects
|
61.54 percentage of subjects
|
66.67 percentage of subjects
|
58.33 percentage of subjects
|
63.64 percentage of subjects
|
63.64 percentage of subjects
|
|
Sensitivity/Specificity/Negative Predictive Value (NPV)/Positive Predictive Value (PPV) at Baseline, 12, and 24 Months in the Detection of Significant Brain ß-amyloid Plaque Load in Patients With MCI Progressing to AD Compared to Those Who do Not Progress
Positive Predictive value
|
60.71 percentage of subjects
|
65.52 percentage of subjects
|
68.00 percentage of subjects
|
61.54 percentage of subjects
|
63.64 percentage of subjects
|
60.00 percentage of subjects
|
|
Sensitivity/Specificity/Negative Predictive Value (NPV)/Positive Predictive Value (PPV) at Baseline, 12, and 24 Months in the Detection of Significant Brain ß-amyloid Plaque Load in Patients With MCI Progressing to AD Compared to Those Who do Not Progress
Negative predictive value
|
88.24 percentage of subjects
|
100.00 percentage of subjects
|
100.00 percentage of subjects
|
93.33 percentage of subjects
|
100.00 percentage of subjects
|
87.50 percentage of subjects
|
Adverse Events
MCI Subjects (Initial Drug Administration)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
MCI Subjects (1st Repeat Drug Administration)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MCI Subjects (2nd Repeat Drug Administration)
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MCI Subjects (Initial Drug Administration)
n=45 participants at risk
Subjects with AEs following the initial administration of florbetaben (BAY94-9172) at the baseline visit
|
MCI Subjects (1st Repeat Drug Administration)
n=41 participants at risk
Subjects with AEs following the second administration of florbetaben (BAY94-9172) at the 12 month visit
|
MCI Subjects (2nd Repeat Drug Administration)
n=36 participants at risk
Subjects with AEs following the third administration of florbetaben (BAY94-9172) at the 24 month visit
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/45 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/41 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
2.8%
1/36 • Number of events 1 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/45 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/41 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
2.8%
1/36 • Number of events 1 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
Other adverse events
| Measure |
MCI Subjects (Initial Drug Administration)
n=45 participants at risk
Subjects with AEs following the initial administration of florbetaben (BAY94-9172) at the baseline visit
|
MCI Subjects (1st Repeat Drug Administration)
n=41 participants at risk
Subjects with AEs following the second administration of florbetaben (BAY94-9172) at the 12 month visit
|
MCI Subjects (2nd Repeat Drug Administration)
n=36 participants at risk
Subjects with AEs following the third administration of florbetaben (BAY94-9172) at the 24 month visit
|
|---|---|---|---|
|
General disorders
Catheter site haemorrhage
|
6.7%
3/45 • Number of events 3 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/41 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/36 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
|
General disorders
Injection site pain
|
20.0%
9/45 • Number of events 9 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/41 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
5.6%
2/36 • Number of events 2 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
|
Nervous system disorders
Burning sensation
|
6.7%
3/45 • Number of events 3 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/41 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/36 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/45 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
7.3%
3/41 • Number of events 3 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
0.00%
0/36 • AEs were defined for the period starting immediately after injection and up to the 7 day follow-up (baseline, 12 month, and 24 month follow-up visit.)
|
Additional Information
Juergen Hirschfeld, Senior Director Regulatory Affairs
Piramal Imaging
Phone: +49 30 461 1246 15
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60