Potential of Florbetapir F 18 PET to Inform Clinical Diagnosis and Management of Patients With Progressive Cognitive Decline

• Sponsor: Avid Radiopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01400425
• Collaborator: (none)
• Enrollment: 239
• Locations: 18
• Arm: 1
• Duration (Months): 12
• Patients Per Site: 13.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The study is designed to evaluate whether a florbetapir F 18 PET scan can impact clinical thinking when physicians are determining the likely cause of a subject's cognitive impairment.

Condition or Disease	Intervention/Treatment	Phase
Progressive Cognitive Decline	Drug: florbetapir F 18	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 239 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Potential of Florbetapir F 18 PET to Inform Clinical Diagnosis and Management of Patients With Progressive Cognitive Decline
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Subjects with Progressive Cognitive Decline Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan.

Drug: florbetapir F 18; IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose; Other Names: 18F-AV-45 Amyvid florbetapir

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis and Physician Management Plan After Obtaining a Negative Florbetapir F 18 PET Scan. [6 weeks]

   The impact of a negative florbetapir F 18 PET scan on a physician's clinical diagnosis and management of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a negative florbetapir scan that led to a change in hypothetical clinical diagnosis and physician management plans are presented below. A negative florbetapir PET scan is indicative of none to sparse β-amyloid neuritic plaque density according to the modified Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Secondary Outcome Measures

1. Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis and Physician Management Plan After Obtaining a Positive Florbetapir F 18 PET Scan [6 weeks]

   The impact of a positive florbetapir F 18 PET scan on a physician's clinical diagnosis and management of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a positive florbetapir scan that led to a change in hypothetical clinical diagnosis and physician management plans are presented below. A positive florbetapir PET scan is indicative of moderate to frequent β-amyloid neuritic plaque density according to the modified Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

2. Change in Confidence of the Clinical Diagnosis [6 weeks]

   Change in confidence of the clinical diagnosis prior to obtaining a florbetapir F 18 PET scan to the confidence after obtaining a florbetapir F 18 PET scan among subjects in whom the clinical diagnosis remains unchanged. Confidence levels were self-determined by physicians based on their diagnostic certainty and ranged from 0-100%. The mean (SD) change in confidence reflects the average change in diagnostic confidence along the 0-100% scale for the 62 subjects analyzed.

3. Change in Physician Management Plans [6 weeks]

   Determine the percentage of subjects that had at least one hypothetical change between pre and post scan physician management plans. Change in management is defined as the number of subjects prescribed different item-wise plans at the two assessments divided by the total number of subjects in the population with both a pre and post florbetapir F 18 PET scan physician management plan.

Other Outcome Measures

1. Item Wise Changes in Physician Management Plan [6 weeks]

   This outcome analyzed the percentage of subjects who had a hypothetical change in one of the medication or diagnostic categories listed below after receiving a florbetapir scan.

2. Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis After Obtaining a Florbetapir F 18 PET Scan. [6 weeks]

   The impact of a florbetapir F 18 PET scan on a physician's clinical diagnosis of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a florbetapir scan that led to a change in hypothetical clinical diagnosis is presented below.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are one of the following:

1. Group A: Recently completed (within the past 18 months) a comprehensive clinical evaluation for progressive cognitive decline.

2. Group B: Currently being evaluated for progressive cognitive decline with further clinical or laboratory testing still planned.

• Have a site enrolling physician who has

1. less than high confidence in their diagnosis for the subject related to the cognitive decline at the time of enrollment. The level of confidence in the diagnosis should be rated by the physician as less than 85%, and should be interpreted as the physician estimating that their diagnosis will be correct in less than 85% of patients with the same presentation as the subject; and

2. suspicion that the subject's cognitive decline is caused, at least in part, by Alzheimer's disease. The level of suspicion should be rated by the physician as there being at least 15% of patients with the same presentation as the subject would have Alzheimer's disease;

• Can tolerate a 10 minute PET scan. The Principal Investigator will carefully assess each subject and use sound medical judgment to determine whether the subject can tolerate the PET scan procedure;

• Have the ability to cooperate and comply with all study procedures;

• Have a study partner willing to accompany the subject on all of the study visits; and

• Give informed consent for study procedures (If the subject is incapable of giving informed consent, the subject's designated decision maker may consent on behalf of the subject but the subject must still confirm assent. This person may serve as the study partner as well).

Exclusion Criteria:

• Subject or site enrolling physician knows the result of a previous amyloid imaging scan.

• Are considered medically unstable;

• Require additional laboratory tests or workup between enrollment and completion of the florbetapir F 18 PET scan;

• Have a clinically significant infectious disease, including Acquired Immunodeficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection;

• Are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days;

• Have ever participated in an experimental study with an amyloid targeting agent unless it can be documented that the subject received only placebo during the course of the trial;

• Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session; or

• Are females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Females of childbearing potential must not be pregnant (negative serum β-hCG at the time of screening and negative urine β-hCG on the day of imaging) or breast feeding at screening. Females must avoid becoming pregnant, and must agree to refrain from sexual activity or to use reliable contraceptive methods such as prescribed birth control or intrauterine device (IUD) for 24 hours following administration of florbetapir F 18.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85006
2	Research Site	Sun City	Arizona	United States	85351
3	Research Site	San Francisco	California	United States	94109
4	Research Site	Boulder	Colorado	United States	80304
5	Research Site	Boynton Beach	Florida	United States	33486
6	Research Site	Clearwater	Florida	United States	33756
7	Research Site	Fort Myers	Florida	United States	33912
8	Research Site	West Palm Beach	Florida	United States	33407
9	Research Site	Shreveport	Louisiana	United States	71130
10	Research Site	Quincy	Massachusetts	United States	02169
11	Research Site	Las Vegas	Nevada	United States	89121
12	Research Site	New York	New York	United States	10021
13	Research Site	Patchogue	New York	United States	11772
14	Research Site	Durham	North Carolina	United States	27705
15	Research Site	Greensboro	North Carolina	United States	27401
16	Research Site	Providence	Rhode Island	United States	02903
17	Research Site	Providence	Rhode Island	United States	02906
18	Research Site	Houston	Texas	United States	77042

Sponsors and Collaborators

• Avid Radiopharmaceuticals

Investigators

• Study Director: Chief Medical Officer, Avid Radiopharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Avid Radiopharmaceuticals
• ClinicalTrials.gov Identifier: NCT01400425
• Other Study ID Numbers: 18F-AV-45-A17
• First Posted: Jul 22, 2011
• Last Update Posted: Mar 29, 2013
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Cognitive Dysfunction

Study Results

Participant Flow

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Period Title: Overall Study
STARTED	239
COMPLETED	229
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Overall Participants	229
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 10.5%
>=65 years	205 89.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.1 (8.1)
Sex: Female, Male (Count of Participants)
Female	114 49.8%
Male	115 50.2%
Region of Enrollment (participants) [Number]
United States	229 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis and Physician Management Plan After Obtaining a Negative Florbetapir F 18 PET Scan.
Description	The impact of a negative florbetapir F 18 PET scan on a physician's clinical diagnosis and management of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a negative florbetapir scan that led to a change in hypothetical clinical diagnosis and physician management plans are presented below. A negative florbetapir PET scan is indicative of none to sparse β-amyloid neuritic plaque density according to the modified Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

116 of 229 subjects with progressive cognitive decline received a negative florbetapir scan.

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Measure Participants	116
Change in Clinical Diagnosis	56.9
Change in Physician Management Plan	81.9

2. Secondary Outcome

Title	Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis and Physician Management Plan After Obtaining a Positive Florbetapir F 18 PET Scan
Description	The impact of a positive florbetapir F 18 PET scan on a physician's clinical diagnosis and management of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a positive florbetapir scan that led to a change in hypothetical clinical diagnosis and physician management plans are presented below. A positive florbetapir PET scan is indicative of moderate to frequent β-amyloid neuritic plaque density according to the modified Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

113 out of 229 subjects with progressive cognitive decline received a positive florbetapir scan.

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Measure Participants	113
Change in Clinical Diagnosis	52.2
Change in Physician Management Plan	92.0

3. Other Pre-specified Outcome

Title	Item Wise Changes in Physician Management Plan
Description	This outcome analyzed the percentage of subjects who had a hypothetical change in one of the medication or diagnostic categories listed below after receiving a florbetapir scan.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The number of subjects analyzed for each reporting group is determined by scan status. There were 229 total subjects with progressive cognitive decline of whom 113 received a positive florbetapir scan and 116 received a negative florbetapir scan.

Arm/Group Title	Subjects With Progressive Cognitive Decline	Subjectss With a Positive Scan	Subjects With a Negative Scan
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.	Subjects with progressive cognitive decline that received a positive florbetapir scan.	Subjects with progressive cognitive decline that received a negative scan.
Measure Participants	229	113	116
AD Medication	31.0	31.9	30.2
Psychiatric Medication	7.4	3.5	11.2
Refer to Clinical Trial	16.2	22.1	10.3
Brain Structural Imaging (CT/MRI)	14.0	15.0	12.9
Lumbar Puncture	10.5	8.8	12.1
Neuropsychologic Testing	22.7	23.9	21.6
FDG PET	10.0	10.6	9.5
ApoE Genotype	5.2	5.3	5.2
Lab Test	7.9	10.6	5.2

4. Secondary Outcome

Title	Change in Confidence of the Clinical Diagnosis
Description	Change in confidence of the clinical diagnosis prior to obtaining a florbetapir F 18 PET scan to the confidence after obtaining a florbetapir F 18 PET scan among subjects in whom the clinical diagnosis remains unchanged. Confidence levels were self-determined by physicians based on their diagnostic certainty and ranged from 0-100%. The mean (SD) change in confidence reflects the average change in diagnostic confidence along the 0-100% scale for the 62 subjects analyzed.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The hypothetical clinical diagnosis remained unchanged in 62 of 229 subjects who received a florbetapir scan.

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Measure Participants	62
Mean (Standard Deviation) [Percent Change in Confidence]	23 (11.9)

5. Secondary Outcome

Title	Change in Physician Management Plans
Description	Determine the percentage of subjects that had at least one hypothetical change between pre and post scan physician management plans. Change in management is defined as the number of subjects prescribed different item-wise plans at the two assessments divided by the total number of subjects in the population with both a pre and post florbetapir F 18 PET scan physician management plan.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

All subjects with progressive cognitive decline who have received a florbetapir scan.

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Measure Participants	229
Number (95% Confidence Interval) [Percentage of subjects]	86.9

6. Other Pre-specified Outcome

Title	Percentage of Subjects Who Undergo a Hypothetical Change in Clinical Diagnosis After Obtaining a Florbetapir F 18 PET Scan.
Description	The impact of a florbetapir F 18 PET scan on a physician's clinical diagnosis of a subject was evaluated on a hypothetical basis because at the start of this study Florbetapir F 18 was an investigational drug and the data collected is for research purposes only. The percentage of subjects who received a florbetapir scan that led to a change in hypothetical clinical diagnosis is presented below.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Subjects who have received a florbetapir scan (either positive or negative).

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
Measure Participants	229
Number (95% Confidence Interval) [Percentage of subjects]	54.6

Adverse Events

Arm/Group Title	Subjects With Progressive Cognitive Decline
Arm/Group Description	Subjects who have previously or are currently being evaluated for progressive cognitive decline. Enrolling physicians must have a confidence of less than 85% in their initial diagnosis of the subject's progressive cognitive decline and that there was at least a 15% chance that the subject's progressive cognitive decline was due to Alzheimer's disease. All subjects who did not complete the study withdrew before receiving a florbetapir F 18 injection and PET scan. Subjects received IV injection, 370 MBq (10 mCi) florbetapir F18, single dose.
All Cause Mortality
	Subjects With Progressive Cognitive Decline
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Subjects With Progressive Cognitive Decline
	Affected / at Risk (%)	# Events
Total	0/229 (0%)
Other (Not Including Serious) Adverse Events
	Subjects With Progressive Cognitive Decline
	Affected / at Risk (%)	# Events
Total	13/229 (5.7%)
Gastrointestinal disorders
Diarrhoea	1/229 (0.4%)	1
Nausea	1/229 (0.4%)	1
Infections and infestations
Urinary tract infection	1/229 (0.4%)	1
Gastroenteritis viral	1/229 (0.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/229 (0.4%)	1
Musculoskeletal stiffness	1/229 (0.4%)	1
Nervous system disorders
Headache	4/229 (1.7%)	4
Balance disorder	1/229 (0.4%)	1
Crying	1/229 (0.4%)	1
Dizziness	1/229 (0.4%)	1
Paraesthesia	1/229 (0.4%)	1
Somnolence	1/229 (0.4%)	1
Psychiatric disorders
Anxiety	1/229 (0.4%)	1
Reproductive system and breast disorders
Breast pain	1/229 (0.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.