Trial Outcomes & Findings for Efficacy and Safety Study of ELND005 as a Treatment for Agitation and Aggression in Alzheimer's Disease (NCT NCT01735630)

Last Updated: 2019-10-21

Results Overview

The NPI-C (de Medeiros et al 2010) is a validated and reliable behavioral measure that assesses psychopathology in dementia subjects. It evaluates 14 neuropsychiatric disturbances common in dementia.Higher scores on the NPI-C are associated with a greater clinical severity of symptoms. The NPI-C Agitation and Aggression score ranges from 0-63. The analysis of the NPI-C A+A score was performed on the mITT population.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

350 participants

Primary outcome timeframe

Week 12

Results posted on

2019-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	ELND005 ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo Matched placebo BID for 12 weeks Placebo
Overall Study STARTED	175	175
Overall Study COMPLETED	157	157
Overall Study NOT COMPLETED	18	18

Reasons for withdrawal

Reasons for withdrawal
Measure	ELND005 ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo Matched placebo BID for 12 weeks Placebo
Overall Study Adverse Event	8	7
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1
Overall Study Sponsor Decision	2	1
Overall Study Withdrawal by Subject	7	9

Baseline Characteristics

Efficacy and Safety Study of ELND005 as a Treatment for Agitation and Aggression in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ELND005 n=175 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=175 Participants Matched placebo BID for 12 weeks Placebo	Total n=350 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	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Age, Categorical >=65 years	162 Participants n=5 Participants	155 Participants n=7 Participants	317 Participants n=5 Participants
Age, Continuous	76.2 years STANDARD_DEVIATION 7.89 • n=5 Participants	75.9 years STANDARD_DEVIATION 8.51 • n=7 Participants	76.0 years STANDARD_DEVIATION 8.19 • n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	100 Participants n=7 Participants	195 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	75 Participants n=7 Participants	155 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	22 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) White	155 Participants n=5 Participants	151 Participants n=7 Participants	306 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Canada	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment United States	153 participants n=5 Participants	152 participants n=7 Participants	305 participants n=5 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Spain	13 participants n=5 Participants	10 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: mITT

Outcome measures

Outcome measures
Measure	ELND005 n=157 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=155 Participants Matched placebo BID for 12 weeks Placebo
Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A).	-4.3 units on a scale Standard Error 0.7	-4.2 units on a scale Standard Error 0.7

SECONDARY outcome

Timeframe: Week 12

Population: mITT population with available data for Modified-ADCS-CGIC Agitation Scores

The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) is a widely used scale for the global assessment of change in AD trials.It is a 7-point Likert scale that ranges from marked improvement scored as 1 to marked worsening scored as 7, with no change scored as 4. The range is from 1 to 7. Higher scores indicate worsening agitation.

Outcome measures

Outcome measures
Measure	ELND005 n=156 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=157 Participants Matched placebo BID for 12 weeks Placebo
Change From Baseline in Modified-ADCS-CGIC Agitation Scores	3.6 units on a scale Standard Error 0.1	3.4 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Week 12

Population: mITT population with available data for NPI Total Scores

The NPI (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia subjects. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and appetite and eating abnormalities. Higher scores on the NPI are associated with greater frequency and severity of symptoms. The scale range is 0-144.

Outcome measures

Outcome measures
Measure	ELND005 n=157 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=154 Participants Matched placebo BID for 12 weeks Placebo
Change From Baseline in NPI Total Scores	-14.38 units on a scale Standard Error 1.69	-15.12 units on a scale Standard Error 1.71

SECONDARY outcome

Timeframe: Week 12

Population: mITT population with available data for MMSE Scores

The Mini-Mental State Exam (MMSE) (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of products approved for the treatment of AD. The score can range from 0 to 30, with lower scores indicating greater impairment in function.

Outcome measures

Outcome measures
Measure	ELND005 n=157 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=154 Participants Matched placebo BID for 12 weeks Placebo
Change From Baseline in MMSE Scores	-0.3 units on a scale Standard Error 0.2	-0.4 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Week 12

Population: mITT population with available data for ADCS-ADL Scores

The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (Galasko et al 1997) is a functional assessment that measures instrumental and basic activities of daily living. The total score for the 23-item ADCS-ADL ranges from 0 to 78 points, with lower scores indicating greater impairment in function.

Outcome measures

Outcome measures
Measure	ELND005 n=156 Participants ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=155 Participants Matched placebo BID for 12 weeks Placebo
Change From Baseline in ADCS-ADL Scores	-1.458 units on a scale Standard Error 0.7	-2.229 units on a scale Standard Error 0.7

Adverse Events

ELND005

Serious events: 17 serious events

Other events: 97 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Aleksandra Pastrak, MD, PhD, Vice President Clinical Development

Transition Therapeutics Ireland Limited

Phone: +1 416 263 1227

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	ELND005 n=175 participants at risk ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=175 participants at risk Matched placebo BID for 12 weeks Placebo
Injury, poisoning and procedural complications Fall	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Acetabulum fracture	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Ankle fracture	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Hip fracture	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Humerus fracture	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Rib fracture	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Sepsis	1.7% 3/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Urinary tract infection	1.7% 3/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Pneumonia	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Urinary tract infection enterococcal	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Convulsion	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Cerebellar infarction	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Syncope	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Renal and urinary disorders Renal failure acute	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Renal and urinary disorders Urinary retention	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Cardiac disorders Cardiac failure congestive	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Gastrointestinal disorders Nausea	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Gastrointestinal disorders Vomiting	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Hepatobiliary disorders Cholelithiasis	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Psychiatric disorders Homocidal ideation	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Psychiatric disorders Psychotic disorder	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.00% 0/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study

Measure	ELND005 n=175 participants at risk ELND005 film coated tablets, BID for 12 weeks ELND005	Placebo n=175 participants at risk Matched placebo BID for 12 weeks Placebo
Psychiatric disorders Agitation	8.0% 14/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	7.4% 13/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Psychiatric disorders Insomnia	2.9% 5/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	4.0% 7/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Gastrointestinal disorders Diarrhoea	8.0% 14/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	2.9% 5/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Gastrointestinal disorders Vomiting	2.9% 5/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	2.9% 5/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Gastrointestinal disorders Constipation	2.3% 4/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Urinary tract infection	6.9% 12/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	4.0% 7/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Infections and infestations Bronchitis	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	2.9% 5/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Dizziness	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	4.0% 7/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Lethargy	3.4% 6/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Somnolence	1.7% 3/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	2.3% 4/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Nervous system disorders Headache	2.3% 4/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Fall	6.3% 11/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	5.1% 9/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Injury, poisoning and procedural complications Contusion	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	4.0% 7/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Respiratory, thoracic and mediastinal disorders Cough	4.0% 7/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	1.1% 2/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
Metabolism and nutrition disorders Decreased appetite	1.7% 3/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	2.3% 4/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study
General disorders Gait disturbance	2.3% 4/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study	0.57% 1/175 • Adverse events were recorded for each patient starting from the time the consent form was signed until the completion of the study