Trial Outcomes & Findings for 16w Interventional Study on Titration and Dose/Efficacy Assessment of Exelon in Chinese Alzheimer's Disease Patients (NCT NCT01948791)

NCT ID: NCT01948791

Last Updated: 2017-02-13

Results Overview

The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) was used to measure change in cognitive function. Alzheimer's disease assessment scale (ADAS) is a scale to measure specific cognitive and behavior disorders in Alzheimer disease (AD) patients. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) provides a total score range 0-70, and consists of 11 items with lower score indicating lighter impairment and higher total scores indicating more impairment. A negative change score indicates improvement from baseline. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

222 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2017-02-13

Participant Flow

222 patients were screened/enrolled to this study but 41 did not receive study drug.

The Intention analysis set consists of 165 patients who received at least 1 treatment \& had at least 1 assessment on primary efficacy variables.

Participant milestones

Participant milestones
Measure	ENA713 Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Overall Study STARTED	222
Overall Study COMPLETED	151
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Reasons for withdrawal
Measure	ENA713 Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Overall Study Adverse Event	12
Overall Study Lack of Efficacy	3
Overall Study Protocol Violation	2
Overall Study Withdrawal by Subject	5
Overall Study Lost to Follow-up	6
Overall Study Management issues	1
Overall Study Others	7
Overall Study Screening failure	35

Baseline Characteristics

16w Interventional Study on Titration and Dose/Efficacy Assessment of Exelon in Chinese Alzheimer's Disease Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ENA713 n=165 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Age, Continuous	69.6 Years STANDARD_DEVIATION 8.4 • n=5 Participants
Gender Female	101 Participants n=5 Participants
Gender Male	64 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: The Per Protocol (PP) population included all patients who had been enrolled to receive treatment, and who had received at least 1 dose of study drug, had 1 baseline assessment \& at least 1 post-baseline efficacy assessment for primary efficacy variable within the Week 16 visit window, and had no major protocol violations.

Outcome measures

Outcome measures
Measure	ENA713 n=151 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Mean Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog)	-2.0 units on a scale Interval -3.0 to 1.1

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: The Per Protocol (PP) population included all patients who had been enrolled to receive treatment, had received at least 1 dose of study drug, had 1 baseline assessment \& at least 1 post-baseline efficacy assessment for primary efficacy variable within the Week 16 visit window \& had no major protocol violations.

ADCS-ADL is a scale based on caregiver's assessment of patient's activities of daily life. It is used in clinical studies on dementia \& consists of 23 items and is designed to assess patient's basic \& instrumental activities of daily life, such as the abilities necessary for personal care, communicating \& interacting with other people, maintaining a household, conducting hobbies \& interests, \& making judgments \& decisions. Response to each item is obtained by interview with the caregiver. The basic activities of daily life domain includes mandatory options for best response, or "yes" or "no" questions with separate sub-questions. Higher score \& more "yes" answers indicate better level of self-care of patient. Therefore the higher the total score is, the better the patient's functions. The total score is the sum of the scores of all the items \& sub-questions,\& ranges from 0 to 78. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated.

Outcome measures

Outcome measures
Measure	ENA713 n=151 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score	0.9 units on a scale Interval -0.5 to 2.3

SECONDARY outcome

Timeframe: Baseline, Week 16

MMSE was used to determine patient's eligibility to participate, is an easy \& practical screening test to identify cognitive disorders. Test consists of 2 parts: language (time orientation, registration \& attention) \& performance (recall, response to written/verbal commands, writing ability \& reproduction of complex polygons); total score range: 0-30; higher score = better function. Positive change score = improvement from baseline. To meet eligibility criteria, patient's MMSE total score at screening had to be 10-26 (inclusive). Interpretation of MMSE by 4 methods: Single Cut0ff: \<24=abnormal; Range: \<21=Increased odds of dementia; \>25=Decreased odds of dementia; Education: 21- abnormal for 8th grade education, \<23=abnormal for high school education, \<24=abnormal for college education; Severity: 24-30=no cognitive impairment, 18-23=mild cognitive impairment, 0-17=severe cognitive impairment. 2-sided 95% CI of difference in means between baseline \& post-baseline values were calculated

Outcome measures

Outcome measures
Measure	ENA713 n=151 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Change From Baseline in Mini-Mental State Examination (MMSE)	0.3 units on a scale Interval -0.4 to 0.8

SECONDARY outcome

Timeframe: Baseline, Week 16

This scale assesses a larger scope of the behavior problems/disorders experienced in dementia patients, and identifies the frequency \& severity of the behavior disorders, \& allows rapid assessment using screening questions. 10 questions in behavior domain \& 2 in autonomic nervous system domain were assessed by the investigator interviewing with the caregiver. The NPI-12 total score is the total score of the 12 items, among which the score for each domain is the product of frequency (range: 1-4 points) and severity (range: 1-3 points). The highest score for each domain is 12 points and all the domains have the same weight. Therefore the range of NPI-12 total score is 0-144 points. The NPI-10 total score is the total score of the first 10 items 0-120, which constitute the original form of this scale. A higher NPI total score indicates more severe behavior disorder. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated.

Outcome measures

Outcome measures
Measure	ENA713 n=151 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Score NPI-10	-3.6 units on a scale Interval -5.3 to -1.9
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Score NPI-12	-4.0 units on a scale Interval -6.2 to -1.9

SECONDARY outcome

Timeframe: Baseline, Week 16

CBI, formulated by Novak and Guest in 1989, is a relatively complete and effective scale to measure caregiver burden that has been extensively adopted internationally. CBI has a total of 24 items in 5 domains, i.e., time dependency items (items 1-5), development items (items 6-10), physical health items (items 11-14), social relations items (items 15-18), and emotional heath items (items 19-24). Each item is scored on a 5-point scale based on the intensity of burden (0-4 points), so that the total score is 0-96, a higher score indicating heavier burden. It is a self-administered scale that takes about 10-15 minutes to complete. Two-sided 95% CI of the difference in the means between baseline and post-baseline values were calculated.

Outcome measures

Outcome measures
Measure	ENA713 n=151 Participants Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Change From Baseline in Caregiver Burden Inventory (CBI) Score	-1.4 units on a scale Interval -3.1 to 0.4

Adverse Events

ENA713

Serious events: 7 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ENA713 n=181 participants at risk Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Cardiac disorders Arteriosclerosis coronary artery	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Infections and infestations Urinary tract infection	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Ankle fracture	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Brain contusion	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Contusion	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Patella fracture	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Pneumocephalus	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Pulmonary contusion	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Rib fracture	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Skin abrasion	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Skull fractured base	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Soft tissue injury	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Nervous system disorders Brain injury	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Nervous system disorders Dizziness	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Nervous system disorders Subarachnoid haemorrhage	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Reproductive system and breast disorders Uterine prolapse	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Vascular disorders Venous thrombosis limb	0.55% 1/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.

Other adverse events

Other adverse events
Measure	ENA713 n=181 participants at risk Patients had a dose escalation from 3mg/d to 12mg/d to reach individual tolerated dosage during the titration period of 12 weeks.
Gastrointestinal disorders Abdominal discomfort	5.0% 9/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Gastrointestinal disorders Diarrhoea	7.2% 13/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Gastrointestinal disorders Nausea	20.4% 37/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Gastrointestinal disorders Vomiting	16.6% 30/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Metabolism and nutrition disorders Decreased appetite	7.7% 14/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Nervous system disorders Dizziness	7.2% 13/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.
Nervous system disorders Headache	3.3% 6/181 The safety set consists of 181 patients who received at least one drug treatment and had post-baseline safety assessments.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER