Trial Outcomes & Findings for Comparative Research of Alzheimer's Disease Drugs (NCT NCT01362686)

Last Updated: 2017-02-27

Results Overview

We are not seeking to establish efficacy of these three medications for the indication of Alzheimer's disease. Each of these medications already has FDA-approval for Alzheimer's. The primary outcome measure is the discontinuation rate among the three medications. Based on previous systematic reviews, these rates are reportedly in the range of 30% by 12 weeks compared with placebo. We will determine the approximate date of discontinuation by self-reports from the caregiver through the telephone-based interview at 6, 12, and 18 weeks.

Recruitment status

TERMINATED

Study phase

Target enrollment

200 participants

Primary outcome timeframe

6, 12, and 18 week interviews from enrollment

Results posted on

2017-02-27

Participant Flow

Recruitment took place from 2011-2014. Recruitment took place in geriatric and memory care specialty clinics in an urban setting. Registered nurses, nurse practitioners, and research assistants completed the recruitment and informed consent procedures.

The enrollment goal in the original protocol of the study was 200 patient-caregiver dyads. 200 were enrolled, but it was discovered that 4 dyads were ineligible after enrollment and were not randomized or included in the study which brings the total enrollment to 196. Recruitment was then terminated due to low enrollment rate.

Participant milestones

Participant milestones
Measure	Donepezil See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Overall Study STARTED	67	66	63
Overall Study COMPLETED	59	54	53
Overall Study NOT COMPLETED	8	12	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparative Research of Alzheimer's Disease Drugs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil n=67 Participants See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine n=66 Participants See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine n=63 Participants See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Total n=196 Participants Total of all reporting groups
Age, Continuous	79.1 years STANDARD_DEVIATION 7.6 • n=5 Participants	80.1 years STANDARD_DEVIATION 9.6 • n=7 Participants	81.6 years STANDARD_DEVIATION 7.8 • n=5 Participants	80.2 years STANDARD_DEVIATION 8.4 • n=4 Participants
Gender Female	19 Participants n=5 Participants	20 Participants n=7 Participants	12 Participants n=5 Participants	51 Participants n=4 Participants
Gender Male	48 Participants n=5 Participants	46 Participants n=7 Participants	51 Participants n=5 Participants	145 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6, 12, and 18 week interviews from enrollment

Outcome measures

Outcome measures
Measure	Donepezil n=67 Participants See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine n=66 Participants See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine n=63 Participants See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Discontinuation Rates	26 participants	35 participants	37 participants

SECONDARY outcome

Timeframe: Baseline, 6, 12, 18 week interviews from enrollment

The NPI is based on a structured interview administered to an informal caregiver and has been adopted by the Alzheimer's Disease Cooperative Studies Group to obtain information on the presence of psychopathology in behavioral areas including delusions, apathy, hallucinations, disinhibition, agitation, depression, aberrant motor behavior, anxiety, night-time behavior, and euphoria.9 For each of 12 symptoms, if the caregiver reports the presence of psychopathology, a frequency and severity score are multiplied to yield a possible item score range of 0-12, and a possible total score range of 0-144. The NPI can be used to assess changes in the patient's behavior over the past month. The NPI also assesses the level of caregiver distress attributable to each of the 12 patient behaviors, with a possible total caregiver distress score range of 0-60. Higher scores indicate higher severity of psychopathology and caregiver disress. The NPI has excellent reliability and validity.

Outcome measures

Outcome measures
Measure	Donepezil n=59 Participants See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine n=58 Participants See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine n=54 Participants See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Neuropsychiatric Inventory (NPI) 6 WeekNPI Patient	12.71 units on a scale Standard Deviation 17.10	9.42 units on a scale Standard Deviation 13.21	8.63 units on a scale Standard Deviation 11.73
Neuropsychiatric Inventory (NPI) 6 Week NPI Caregiver	5.94 units on a scale Standard Deviation 9.09	4.40 units on a scale Standard Deviation 5.80	3.91 units on a scale Standard Deviation 4.86
Neuropsychiatric Inventory (NPI) 12 Week NPI Patient	9.62 units on a scale Standard Deviation 13.56	8.40 units on a scale Standard Deviation 13.27	5.24 units on a scale Standard Deviation 5.54
Neuropsychiatric Inventory (NPI) 12 Week NPI Caregiver	5.66 units on a scale Standard Deviation 7.34	4.33 units on a scale Standard Deviation 6.01	2.22 units on a scale Standard Deviation 2.86
Neuropsychiatric Inventory (NPI) 18 Week NPI Patient	9.06 units on a scale Standard Deviation 13.87	10.67 units on a scale Standard Deviation 13.85	7.26 units on a scale Standard Deviation 7.36
Neuropsychiatric Inventory (NPI) 18 Week NPI Caregiver	5.56 units on a scale Standard Deviation 7.66	6.22 units on a scale Standard Deviation 7.56	2.89 units on a scale Standard Deviation 3.17

SECONDARY outcome

Timeframe: baseline, 6, 12, and 18 week interviews

The current HABC-Monitor includes 30 items covering four clinically relevant domains of dementia, ie, cognitive, functional, behavioral, and psychological symptoms, and caregiver quality of life. For brevity and practical use in the clinical setting, each item on the four scales was designed to have the same item response options consisting of four categories that use the frequency of the target problem in the past 2 weeks. The HABC- Monitor took approximately 6 minutes to complete. The scores of the four scales are summed to create the total scores which were used in this analysis.The higher the total score, the higher the level of self reported caregiver burden. The minimum score is 0 and the maximum score is 90.

Outcome measures

Outcome measures
Measure	Donepezil n=59 Participants See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine n=58 Participants See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine n=54 Participants See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Healthy Aging Brain Care (HABC)-Monitor Baseline HABC	18.76 units on a scale Standard Deviation 13.64	18.34 units on a scale Standard Deviation 11.91	16.61 units on a scale Standard Deviation 11.49
Healthy Aging Brain Care (HABC)-Monitor 6 Week HABC	18.61 units on a scale Standard Deviation 15.16	19.16 units on a scale Standard Deviation 12.72	16.43 units on a scale Standard Deviation 10.52
Healthy Aging Brain Care (HABC)-Monitor 12 Week HABC	16.04 units on a scale Standard Deviation 13.41	18.00 units on a scale Standard Deviation 15.71	13.63 units on a scale Standard Deviation 9.34
Healthy Aging Brain Care (HABC)-Monitor 18 Week HABC	16.90 units on a scale Standard Deviation 15.30	19.92 units on a scale Standard Deviation 14.28	15.80 units on a scale Standard Deviation 9.01

Adverse Events

Donepezil

Serious events: 32 serious events

Other events: 40 other events

Deaths: 0 deaths

Galantamine

Serious events: 29 serious events

Other events: 42 other events

Deaths: 0 deaths

Rivastigmine

Serious events: 27 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Noll Campbell

Regenstrief Insitute

Phone: 317-274-9051

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Donepezil n=59 participants at risk See intervention note. Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Galantamine n=54 participants at risk See intervention note. Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.	Rivastigmine n=53 participants at risk See intervention note. Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.
Respiratory, thoracic and mediastinal disorders Asthma	3.4% 2/59 • Number of events 2 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	9.3% 5/54 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	3.8% 2/53 • Number of events 2 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Gastrointestinal disorders Diahrrhea	22.0% 13/59 • Number of events 17 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	9.3% 5/54 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	13.2% 7/53 • Number of events 8 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Nervous system disorders Dizziness	6.8% 4/59 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	11.1% 6/54 • Number of events 10 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	15.1% 8/53 • Number of events 9 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
General disorders Fainting	3.4% 2/59 • Number of events 2 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	1.9% 1/54 • Number of events 1 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	3.8% 2/53 • Number of events 2 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
General disorders Falls	0.00% 0/59 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	0.00% 0/54 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.7% 3/53 • Number of events 3 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Cardiac disorders Fast or Slowed Heart Rate	8.5% 5/59 • Number of events 7 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	0.00% 0/54 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	7.5% 4/53 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
General disorders Feeling Tired	11.9% 7/59 • Number of events 10 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	9.3% 5/54 • Number of events 7 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.7% 3/53 • Number of events 3 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Nervous system disorders Headache	10.2% 6/59 • Number of events 7 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	7.4% 4/54 • Number of events 6 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.7% 3/53 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
General disorders Incontinence	8.5% 5/59 • Number of events 6 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	11.1% 6/54 • Number of events 9 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	9.4% 5/53 • Number of events 6 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Cardiac disorders Irregular Heart Beat	6.8% 4/59 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.6% 3/54 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.7% 3/53 • Number of events 3 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Metabolism and nutrition disorders Lack of Interest in Eating	15.3% 9/59 • Number of events 10 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.6% 3/54 • Number of events 3 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	7.5% 4/53 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Musculoskeletal and connective tissue disorders Muscle Cramps	8.5% 5/59 • Number of events 7 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	11.1% 6/54 • Number of events 8 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.7% 3/53 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Psychiatric disorders Nightmares	10.2% 6/59 • Number of events 8 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	5.6% 3/54 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	1.9% 1/53 • Number of events 1 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Nervous system disorders Pain	5.1% 3/59 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	13.0% 7/54 • Number of events 10 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	7.5% 4/53 • Number of events 5 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Respiratory, thoracic and mediastinal disorders Runny Nose	13.6% 8/59 • Number of events 9 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	9.3% 5/54 • Number of events 6 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	7.5% 4/53 • Number of events 4 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Nervous system disorders Seizure or Fits	1.7% 1/59 • Number of events 1 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	1.9% 1/54 • Number of events 1 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.	0.00% 0/53 • Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.