Conditions: Alzheimer's Disease
Keywords: Alzheimer, Rivastigmine
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 100
Healthy volunteers: no

Brief summary:
This was a multicenter, prospective, phase IV study evaluating safety, tolerability and effectiveness of rivastigmine 27 mg -15 cm\^2 transdermal patch prescribed in patients with severe dementia of the Alzheimer's type as per discretion of treating physician.

Detailed description:
This was a multicenter, prospective, single-arm, open-label, phase IV study to evaluate safety, tolerability and effectiveness of Rivastigmine 27 mg -15 cm\^2 transdermal patch prescribed in patients with severe dementia of the Alzheimer's type as per discretion of treating physician. Male and female patients who were treated according to local routine clinical practice were enrolled in the study upon signing informed consent. The prescription decision was independent of the decision for inclusion in the study.

Arms:
arm 1: 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day

Interventions: intervention 1: Rivastigmine
Intervention descriptions: intervention 1: 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day

Protocol document:
Prot_000.pdf: 
Official Title: 
A Prospective, 16 Week, Phase IV Study to Evaluate 
Safety, Tolerability and Effectiveness in Patients With 
Severe Dementia of the Alzheimer's Type Exposed to 
Rivastigmine (Exelon)15cm2 Transdermal Patch
NCT Number: 
Document Date: Clinical Study Protocol (Version 2.0): 21-December-2016    
NCT02989402 


Clinical Development 
Rivastigmine patch 
Clinical Trial Protocol CENA713DIN01 / NCT02989402
A prospective, 16 week, phase IV study to evaluate safety, 
tolerability and effectiveness in patients with severe dementia of 
the Alzheimer’s type exposed to rivastigmine (Exelon) 15 cm2 
transdermal patch 
Authors: 
, 
 
Document type: 
Clinical Trial Protocol 
Version number: 
V 02 (Original protocol) 
Development phase: 
IV 
Release date: 
21-Dec-2016
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
NCDS Template Version 03-Feb-2012 
PPD
PPD


Novartis 
Confidential 
Page 2 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
Table of contents 
 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of abbreviations ............................................................................................................ 5 
Glossary of terms ................................................................................................................. 6 
Protocol synopsis ................................................................................................................. 8 
1 
Introduction ....................................................................................................................... 11 
1.1 
Background ............................................................................................................ 11 
1.2 
Purpose .................................................................................................................. 11 
2 
Study objectives ................................................................................................................. 12 
2.1 
Primary .................................................................................................................. 12 
2.2 
Secondary objectives ............................................................................................. 12 
2.3 
Exploratory objectives ........................................................................................... 12 
3 
Investigational plan ........................................................................................................... 12 
3.1 
Study design........................................................................................................... 12 
3.2 
Rationale of study design. ...................................................................................... 13 
3.3 
Rationale of dose/regimen, route of administration and duration of treatment. .... 13 
3.4 
Rationale for choice of comparator ....................................................................... 13 
3.5 
Purpose and timing of interim analyses/design adaptations .................................. 13 
3.6 
Risks and benefits .................................................................................................. 13 
4 
Population .......................................................................................................................... 14 
4.1 
Inclusion criteria .................................................................................................... 14 
4.2 
Exclusion criteria ................................................................................................... 15 
5 
Treatment ........................................................................... Error! Bookmark not defined. 
5.1 
Protocol requested treatment ................................................................................. 15 
5.1.1 
Investigational treatment ....................................................................... 15 
5.1.2 
Additional study treatment .................................................................... 15 
5.2 
Treatment arms. ..................................................................................................... 15 
5.3 
Treatment assignment, randomization. .................................................................. 15 
5.4 
Treating the patient ................................................................................................ 15 
5.4.1 
Patient numbering ................................................................................. 15 
5.4.2 
Dispensing the investigational treatment .............................................. 15 
5.4.3 
Handling of study treatment. ................................................................. 15 
5.4.4 
Handling of investigational treatment ................................................... 15 
5.4.5 
Instructions for prescribing and taking study treatment ........................ 16 
5.4.6 
Permitted dose adjustments and interruptions of study treatment ........ 16 


Novartis 
Confidential 
Page 3 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
5.4.7 
Rescue medication ................................................................................ 16 
5.4.8 
Concomitant treatment .......................................................................... 16 
5.4.9 
Prohibited Treatment ............................................................................. 16 
5.4.10 
Discontinuation of study treatment and premature patient 
withdrawal ............................................................................................. 16 
5.4.11 
Emergency breaking of treatment assignment ...................................... 17 
5.4.12 
Study completion and post-study treatment .......................................... 17 
5.4.13 
Early study termination ......................................................................... 17 
6 
Visit schedule and assessments ......................................................................................... 17 
6.1 
Information to be collected on screening failures.................................................. 19 
6.2 
Patient demographics/other baseline characteristics ............................................. 19 
6.3 
Treatment exposure and compliance ..................................................................... 19 
6.4.1 
Efficacy assessment .............................................................................. 19 
6.4.2 
Appropriateness of efficacy assessments .............................................. 20 
6.5 
Safety ..................................................................................................................... 20 
6.5.1 
Physical examination ............................................................................ 20 
6.5.2 
Dermatology examination: .................................................................... 20 
6.5.3 
Vital signs.............................................................................................. 21 
6.5.4 
Height and weight ................................................................................. 21 
6.5.5 
Patch adhesion assessment: ................................................................... 21 
6.5.6 
Laboratory evaluations .......................................................................... 21 
6.5.7 
Appropriateness of safety measurements .............................................. 21 
6.6 
Other assessments .................................................................................................. 22 
6.6.1 
Treatment and compliance: ................................................................... 22 
6.6.2 
Health-related Quality of Life ............................................................... 22 
6.6.3 
Pharmacokinetics .................................................................................. 22 
6.6.4 
Pharmacogenetics/pharmacogenomics ................................................. 22 
6.6.5 
Other biomarkers: .................................................................................. 22 
7 
Safety monitoring .............................................................................................................. 22 
7.1 
Adverse events ....................................................................................................... 22 
7.2 
Serious adverse event reporting ............................................................................. 24 
7.3 
Pregnancy reporting ............................................................................................... 25 
8 
Data review and database management ............................................................................. 25 
8.1 
Site monitoring ...................................................................................................... 25 
8.2 
Data collection ....................................................................................................... 26 
8.3 
Database management and quality control ............................................................ 26 
8.4 
Data Monitoring Committee .................................................................................. 26 


Novartis 
Confidential 
Page 4 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
8.5 
Adjudication Committee ........................................................................................ 26 
9 
Data analysis ...................................................................................................................... 26 
9.1 
Analysis sets .......................................................................................................... 26 
9.2 
Patient demographics and other baseline characteristics ....................................... 27 
9.3 
Treatments ............................................................................................................. 27 
9.4 
Analysis of the primary and key secondary variable(s)......................................... 27 
9.4.1 
Primary Variable ................................................................................... 27 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 27 
9.4.3 
Handling of missing values/censoring/discontinuations. ...................... 27 
9.4.4 
Supportive analyses ............................................................................... 27 
9.5 
Analysis of secondary variables ............................................................................ 27 
9.5.1 
Efficacy variables .................................................................................. 27 
9.5.2 
Safety variables ..................................................................................... 28 
9.5.3 
Resource utilization ............................................................................... 28 
9.5.4 
Health-related Quality of Life ............................................................... 28 
9.5.5 
Pharmacokinetics .................................................................................. 28 
9.5.6 
Pharmacogenetics/pharmacogenomics ................................................. 28 
9.5.7 
Biomarkers ............................................................................................ 28 
9.5.8 
PK/PD ................................................................................................... 28 
9.6 
Interim analyses ..................................................................................................... 28 
9.7 
Sample size calculation .......................................................................................... 28 
10 Ethical considerations ........................................................................................................ 29 
10.1 
Regulatory and ethical compliance ........................................................................ 29 
10.2 
Informed consent procedures ................................................................................. 29 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 29 
10.4 
Publication of study protocol and results............................................................... 30 
11 Protocol adherence ............................................................................................................ 30 
11.1 
Protocol Amendments ........................................................................................... 30 
12 References: ........................................................................................................................ 30 
13 Appendix 1– Caregiver Medication Questionnaire ........................................................... 31 
14 Appendix 2: Patient Instructions for use and handling exelon patch ................................ 34 
 
 
 
 
 


Novartis 
Confidential 
Page 5 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
List of tables 
List of abbreviations 
AE 
Adverse event 
AD                      Alzheimer’s disease   
b.i.d. 
twice a day 
CMQ                 Caregiver Medication Questionnaire 
CRF 
Case Report/Record Form (paper ) 
CPO 
Country Pharma Organization 
CRO 
Contract Research Organization 
ECG 
Electrocardiogram 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
i.v. 
Intravenous 
IRB 
Institutional Review Board 
MMSE                Mini-Mental State Examination  
o.d. 
once a day 
p.o. 
oral 
SAE 
serious adverse event 
 


Novartis 
Confidential 
Page 6 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Glossary of terms 
 
Assessment 
A procedure used to generate data required by the study 
Control drug 
Drugs(s) used as a comparator to reduce assessment bias, 
preserve blinding of investigational drug, assess internal study 
validity, and/or evaluate comparative effects of the investigational 
drug 
Enrollment 
Point/time of patient entry into the study; the point at which 
informed consent must be obtained (i.e. prior to starting any of the 
procedures described in the protocol) 
Epoch  
The planned stage of the subjects’ participation in the study. Each 
epoch serves a purpose in the study as a whole. Typical epochs 
are: determination of subject eligibility, wash-out of previous 
treatments, exposure of subject to treatment or to follow-up on 
subjects after treatment has ended. 
Investigational drug 
The drug whose properties are being tested in the study; this 
definition is consistent with US CFR 21 Section 312.3 and is 
synonymous with “investigational new drug” or “investigational 
medicinal product.” 
Investigational treatment 
All investigational drug(s) whose properties are being tested in the 
study as well as their associated treatment controls.  
This includes any placebos, any active controls, as well as 
approved drugs used outside of their indication/approved dosage 
or tested in a fixed combination.  
Investigational treatment generally does not include other 
treatments administered as concomitant background therapy 
required or allowed by the protocol when used within approved 
indication/dosage 
Medication number 
A unique identifier on the label of each investigational/study drug 
package in studies that dispense medication using an IRT system 
Subject Number  
A number assigned to each patient who enrolls into the study  
Part  
A subdivision of a single protocol into major design components. 
These parts often are independent of each other and have different 
populations or objectives. For example, a single dose design, a 
multiple dose design that are combined into one protocol, or the 
same design with different patient populations in each part. 
Period 
A subdivision of a cross-over study 
Premature patient withdrawal 
Point/time when the patient exits from the study prior to the 
planned completion of all investigational/study treatment 
administration and all assessments (including follow-up) 
Randomization number 
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment 
Stop study participation 
Point/time at which the patient came in for a final evaluation visit or 
when study/investigational treatment was discontinued whichever 
is later 
Study drug/ treatment 
Any single drug or combination of drugs administered to the patient 
as part of the required study procedures; includes investigational 
drug (s), active drug run-ins or background therapy  
Study/investigational treatment 
Point/time when patient permanently stops taking 


Novartis 
Confidential 
Page 7 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
discontinuation 
study/investigational treatment  for any reason; may or may not 
also be the point/time of premature patient withdrawal 
Variable 
Information used in the data analysis; derived directly or indirectly 
from data collected using specified assessments at specified time 
points 
 


Novartis 
Confidential 
Page 8 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Protocol synopsis 
  
Protocol number 
CENA713DIN01 
Title 
A prospective, 16 week, phase IV study to evaluate safety, 
tolerability and effectiveness in patients with severe dementia of the 
Alzheimer’s 
type 
exposed 
to 
rivastigmine 
(Exelon)15cm2 
transdermal patch 
Brief title 
 
Study of safety and effectiveness  of Rivastigmine  in Alzheimer 
patients  
 
Sponsor and Clinical 
Phase 
Novartis  
 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and rationale 
The present phase IV study is mandated by Indian health authority 
(HA) as a part of conditional approval to market authorization of 
rivastigmine 27 mg -15 cm2 transdermal patch for treatment of 
severe dementia secondary to Alzheimer’s disease (AD). The HA 
mandated phase IV study in their approval letter. Due to non- 
availability of Indian data for rivastigmine 27 mg -15 cm2 
transdermal patch in severe dementia secondary to Alzheimer’s 
disease (AD) patients, marketing authorization of the same has been 
granted condition to phase IV study. As per HA letter, interventional 
study is to be conducted. 
Thus the present 16 week study will be conducted to evaluate safety, 
tolerability and effectiveness in patients with severe dementia of the 
Alzheimer’s type exposed to rivastigmine 27 mg -15 cm2 
transdermal patch as mandated by HA. Most frequent AEs in 
ACTION study were application site erythema/ dermatitis and UTI, 
the present study shall assess application site reaction and urine 
examination.  
 
 
Primary Objective(s) 
and Key Secondary 
Objective 
To obtain safety data in patients with severe dementia of the 
Alzheimer’s type treated with rivastigmine 27 mg -15 cm2 
transdermal patch for 16 weeks  
Secondary Objectives 
 
 To assess patients compliance of  rivastigmine 27 mg -15 cm2 
transdermal patch during 16 weeks treatment period 


Novartis 
Confidential 
Page 9 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 To assess the skin tolerability (irritation and adhesion) during 16 
weeks treatment period 
 To assess the proportion of patients with UTI during 16 weeks 
treatment period 
 To evaluate treatment effect by rivastigmine 27 mg -15 cm2 
transdermal patch by assessing the changes in Mini-Mental State 
Examination (MMSE)  
 
To evaluate treatment efficacy by rivastigmine 27 mg -15 cm2 
transdermal patch by assessing the changes in ADCS-Activities of 
Daily Living Inventory – Severe Impairment Version (ADCS-ADL SIV) 
Score 
 
 
Study design 
This is a multicenter, prospective, phase IV study evaluating safety, 
tolerability and effectiveness of rivastigmine 27 mg -15 cm2   
transdermal patch prescribed in patients with severe dementia of 
the Alzheimer’s type as per discretion of treating physician.  
The prescription decision shall be independent of decision for 
inclusion in the study. Patients treated according to local routine 
clinical practice will be enrolled in the study upon signing an 
Informed Consent. Eligibility for study entry will be determined by 
the study investigator, in accordance with the selection criteria 
below. Signing of the Informed Consent defines the study entry 
visit. Routine urine examination shall be done to detect any UTI. 
Compliance to treatment directions shall be reviewed by treating 
investigator at every visit. 
After 8 week and at 16 week, it is expected for the physician to 
follow up as per routine practice in India. The treating physician will 
assess the safety, tolerability and effectiveness of the rivastigmine 
27 mg -15 cm2  transdermal patch and may consider continuing or 
changing the therapy 
Population 
Alzheimer’s disease patients 
Inclusion criteria 
1. Patients willing to participate in the study by providing written 
informed consent. 
2. Patients diagnosed with severe dementia secondary to 
Alzheimer’s disease (AD) 
 
Exclusion criteria 
1. Contraindication as per PI 
2. Patients simultaneously participating in other studies 
 


Novartis 
Confidential 
Page 10 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Investigational and 
reference therapy 
Rivastigmine patch  15cm2 
Efficacy assessments 
 
Mini-Mental State Examination (MMSE) 
 ADCS-Activities 
of 
Daily 
Living 
Inventory 
– 
Severe 
Impairment Version (ADCS-ADL SIV) Score 
 
 
Safety assessments 
 
Urine examination 
 
Skin reaction at patch  
 
Patch adhesion     
 
Adverse events  
Other assessments 
 
Compliance by Caregiver medication 
questionnaire 
 
Data analysis 
The primary safety objective of this study will be assessed by 
collecting adverse events. The key secondary objective of this study 
will be assessed by compliance measured by caregiver 
questionnaire, skin reaction and change in MMSE from baseline 
Key words 
Alzheimer, Rivastigmine, 
 


Novartis 
Confidential 
Page 11 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
1 
Introduction 
1.1 
Background  
1.2 
Purpose  
Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the most prominent 
cognitive disorder of the elderly. The prevalence of AD in people over the age of 65 is 5-10%, 
and increases up to 50% in those over the age of 85 (Small GW, 1995). The Alzheimer’s 
Association estimates that in 2008, as many as 5.2 million Americans have AD (Alzheimer’s 
Association, 2008). 
Multiple deficits of neurotransmitters occur in the brain of AD patients. However, the most 
common is a decrease in levels of acetylcholine (ACh), which is due to a loss of presynaptic 
cholinergic nerve terminals. These cholinergic deficits are most apparent in the areas of the 
brain involved in memory and cognition, i.e., the frontal cortex and hippocampus (Perry et al, 
1978). 
Currently, there are two compounds approved in the US for the treatment of severe dementia 
of the Alzheimer’s type, the cholinesterase inhibitor donepezil and the glutamate modifying 
agent memantine. Both are often used together. With only one agent in each class available to 
treat patients with severe dementia of the Alzheimer’s type, there is significant medical need 
to have other approved agents available, including those that have an alternative route to oral 
administration. 
A number of treatment strategies involving the cholinergic system have been evaluated. 
Cholinesterase inhibitors (ChEIs), including rivastigmine (also known as ENA713 and 
Exelon®), have been shown to be effective in improving cognitive and global functioning in 
mild to moderate AD patients (Kumar et al, 1991; Knapp et al, 1994; Rogers et al, 1998; 
Corey-Bloom et al, 1998; Rösler et al, 1999; Raskind et al, 2000; Tariot et al, 2000). 
Memantine has established efficacy in moderate to severe dementia of the Alzheimer’s type 
(Reisberg et al, 2003; Tariot et al, 2004; van Dyck et al, 2007) and can be used as an 
augmenting agent with ChEIs. 
The need for effective and well-tolerated treatments for AD (both symptomatic and disease 
modifying) remains great. Exelon® transdermal patch, prescribed once-daily, has the potential 
to offer improved caregiver and patient convenience in severe dementia of the Alzheimer’s 
type, which may contribute to an improvement in patient compliance. In addition, this 
formulation is useful for patients unable to take oral medication. Exelon® (rivastigmine) is a 
slowly reversible (pseudo-irreversible), brain selective, dual inhibitor of Acetyl cholinesterase 
(AChE) and Butyryl cholinesterase inhibitors (BuChE) of the carbamate type. Exelon® exerts 
its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing 
the concentration of acetylcholine through reversible cholinesterase inhibition. The present 
study is mandated by Indian health authority (HA) as a part of conditional approval to market 
authorization of rivastigmine 27 mg- 15 cm2 transdermal patch for treatment of severe 
dementia secondary to Alzheimer’s disease (AD).  


Novartis 
Confidential 
Page 12 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Thus the present 16 week study will be conducted to evaluate safety, tolerability and 
effectiveness in patients with severe dementia of the Alzheimer’s type exposed to 
rivastigmine 27 mg -15 cm2 transdermal patch as mandated by HA. Most frequent AEs in 
ACTION study were application site erythema/ dermatitis and UTI, the present study shall 
assess application site reaction and urine examination 
2 
Study objectives 
 
2.1 
Primary  
Primary objective: To obtain safety data in patients with severe dementia of the Alzheimer’s 
type treated with rivastigmine 27 mg -15 cm2 transdermal patch for 16 weeks  
2.2 
Secondary objectives 
Secondary objectives:  
 To assess patients compliance of  rivastigmine 27 mg -15 cm2 transdermal patch during 
16 weeks treatment period 
 To assess the skin tolerability (irritation and adhesion) during 16 weeks treatment period 
 To assess the proportion of patients with UTI during 16 weeks treatment period 
 To evaluate treatment effect by rivastigmine 27 mg -15 cm2 transdermal patch by 
assessing the changes in Mini-Mental State Examination (MMSE)  
 To evaluate treatment efficacy by rivastigmine 27 mg -15 cm2 transdermal patch by 
assessing the changes in ADCS-Activities of Daily Living Inventory – Severe Impairment 
Version (ADCS-ADL SIV) Score 
 
2.3 
Exploratory objectives  
None   
3 
Investigational plan 
3.1 
Study design 
This is a multicenter, prospective, phase IV study evaluating safety, tolerability and 
effectiveness of rivastigmine 27 mg -15 cm2 transdermal patch prescribed in patients with 
severe dementia of the Alzheimer’s type as per discretion of treating physician.  
The prescription decision shall be independent of decision for inclusion in the study. Patients 
treated according to local routine clinical practice will be enrolled in the study upon signing 
an Informed Consent. Eligibility for study entry will be determined by the study investigator, 
in accordance with the selection criteria below. Signing of the Informed Consent defines the 


Novartis 
Confidential 
Page 13 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
study entry visit. Routine urine examination shall be done to detect any UTI. Compliance to 
treatment directions shall be reviewed by treating investigator at every visit. 
After 8 week and at 16 week, it is expected for the physician to follow up as per routine 
practice in India. The treating physician will assess the safety, tolerability and effectiveness 
of the rivastigmine 27 mg -15 cm2 transdermal patch and may consider continuing or 
changing the therapy. 
3.2 
Rationale of study design. 
This is open label study to examine the safety, effectiveness, and tolerability of the treatment 
in routine clinical practice, to determine how the treatment works under ordinary and variable 
conditions, prescribed by clinicians with varying degrees of expertise and practicing across 
the spectrum of health care settings, to treat a heterogeneous group of patients.  
3.3 
Rationale of dose/regimen, route of administration and duration 
of treatment. 
 Dose and regimen is as per approved label in India for rivastigmine. 
3.4 
Rationale for choice of comparator 
No comparator is used in study  
3.5 
Purpose and timing of interim analyses/design adaptations 
Not applicable  
3.6 
Risks and benefits  
 
Rivastigmine is approved for the treatment of mild to moderately severe dementia of the 
Alzheimer type (and in some countries mild to moderately severe dementia associated with 
PD and severe dementia of the Alzheimer’s type). In most cases the drug is used as a 
monotherapy, although in some cases it is used along with memantine. Prescription of the 
medication is initiated at a low dose and increased according to the patient’s response and 
tolerance. Total period prescription numbers of the oral formulations are steadily decreasing 
to be replaced by increasing numbers of prescriptions of the transdermal (Patch) formulations. 
The treatment is initiated at patch 5cm2 and increased to patch 10 cm² after a minimum of 
four weeks of treatment if well tolerated and then, if appropriate to patch 15 cm2.  
 
The benefit of rivastigmine has been seen in multiple clinical trials, in both placebo and 
active-controlled trials (using low dose Exelon as the active comparator). The ability of 
rivastigmine to positively affect the symptoms of AD and Parkinson's disease dementia has 
been demonstrated in six randomized double-blind, placebo-controlled clinical trials with 
4517 patients with mild to moderate AD and in one randomized double blind placebo 
controlled trial with Parkinson's disease dementia with 541 patients. There was one 
(ENA713D2340) active controlled trial in mild to moderate AD with 1582 patients. There was 
one active controlled trial (US44 and US44E1) with extension for severe AD. 
 


Novartis 
Confidential 
Page 14 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
Clinically significant improvement in AD and Parkinson's disease dementia symptoms were 
observed in all but one clinical trial with response rates, in the transdermal formulations, 
achieved predominantly in patch 10 cm² and patch 15 cm2 users. Dementia improvement was 
seen in all tested demographics. The most frequently reported AEs were nausea, vomiting and 
diarrhea. This is consistent with Exelon’s cholinergic effects and with results seen with 
Exelon® capsule. Action study with 15 cem Patch has demonstrated The 13.3 mg/24 h patch 
demonstrated superior efficacy to 4.6 mg/24 h patch on Severe Impairment Battery (SIB) and 
AD Cooperative Study–Activities of Daily Living scale–Severe Impairment Version (ADCS-
ADL-SIV), without marked increase in AEs, suggesting higher-dose patch has a favorable 
benefit-to-risk profile in severe AD.  
 
No pivotal clinical trials are ongoing except for CENA713D2409 which is a PASS drug 
utilization study to assess medication errors and misuse and multiple patch use in particular. 
All identified and potential risk are discussed in the Exelon RMP (version 8.0) and PSUR 24 
(DLP 31 Jan 2016) and no new risks have been added and several have been removed in the 
last 2 PSURs. The sole risk with an ongoing risk minimization strategy is for medication 
errors(specifically multiple patch use) which is currently being actively implemented . 
Previous clinical trial results have been data-mined as a means for expanding MAH 
knowledge of the previously unstudied population of patients with pre-existing renal 
compromise and pre-existing cardiac disorders. No risk for use of rivastigmine in these 
populations has been detected to date. The company is continuing to investigate the increased 
reporting rate of skin reactions in the Japanese population which may result from intensive 
local pharmacovigilance collection techniques and determine if further measures are 
necessary. 
 
The risk benefit ratio for Exelon (oral and transdermal formulations) remains positive. 
4 
Population 
The study population will consist of male and female patients diagnosed with Alzheimer’s 
disease and prescribed with rivastigmine 27mg -15 cm2 transdermal patch as per discretion of 
treating physician. Inclusion and exclusion criteria follow the approved indication and 
contraindications, as mentioned in package insert (PI) in India 
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 
 Patients willing to participate in the study by providing written informed consent. 
 Patients diagnosed with severe dementia secondary to Alzheimer’s disease (AD) 
 Patient’s prescribed with rivastigmine 27mg -15 cm2 transdermal patch as per 
discretion of treating physician  
 


Novartis 
Confidential 
Page 15 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
4.2 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
Exclusion criteria: 
1. Contraindication as per PI 
2. Patients simultaneously participating in other studies 
4.3 
Protocol requested treatment 
4.3.1 
Investigational treatment 
The study will include the following open-label drug: 
Exelon© patch: 15 cm2 patch sizes loaded with 27 mg of rivastigmine 
4.3.2 
Additional study treatment 
No additional treatment beyond investigational treatment is requested for this trial. 
4.4 
Treatment arms. 
 Single arm study 
4.5 
Treatment assignment, randomization. 
 No protocol specific treatment will be assigned to subjects.  
4.6 
Treating the patient 
4.6.1 
Patient numbering  
Each patient is uniquely identified by a Subject Number which is composed by the site 
number assigned by Novartis and a sequential number assigned by the investigator. Once 
assigned to a patient, the Subject Number will not be reused.  
Upon signing the informed consent form, the patient is assigned the next sequential number 
by the investigator. The reason for not being treated will be entered on the Screening Epoch 
Study Disposition CRF. 
4.6.2 
Dispensing the investigational treatment 
 Commercial Novartis drugs will be locally purchased. 
4.6.3 
Handling of study treatment. 
Not applicable.  
4.6.4 
Handling of investigational treatment 
Not applicable. 


Novartis 
Confidential 
Page 16 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
4.6.5 
Instructions for prescribing and taking study treatment 
The investigator should promote compliance by instructing the patient to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the patient’s 
safety and the validity of the study. The patient should be instructed to contact the investigator 
if he/she is unable for any reason to take the study treatment as prescribed. 
Refer to appendix 2 for instruction for applying the patch  
4.6.6 
Permitted dose adjustments and interruptions of study treatment 
 
For patients who are unable to tolerate the protocol-specified dosing scheme, dose  
adjustments and interruptions are permitted in order to keep the patient on study drug. If 
necessary, the patient may be instructed to skip certain doses for a prescribed length of time 
(e.g., skip one or two day’s doses) until tolerability has improved. The following treatment  
adjustment scheme is recommended:  
• If tolerability problem arises: The caregiver should remove the patch(es) on the day 
the tolerability problems arise and skip 1 or 2 days of treatment. 
• Tolerability should be reassessed after the patient has skipped the recommended days 
of treatment.  
• If tolerability problems have improved, and consecutive days of missed doses is ≤ 3 
days, treatment may be restarted at the same DL.  
• If tolerability is still an issue, restart treatment at the next lower DL. 
• The patient should then resume the titration schedule if tolerability issues have 
improved. 
• If subsequent titration again leads to a tolerability problem, doses may again be 
skipped and the DL should be decreased to the next lower DL 
• Further attempts to titrate the dose upward are at the investigator’s discretion (i.e., if 
necessary for tolerability, titration to the target dose need not be achieved) 
4.6.7 
Rescue medication 
Not applicable 
4.6.8 
Concomitant treatment 
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) 
administered after the patient was enrolled into the study must be recorded. 
4.6.9 
Prohibited Treatment 
No prohibited medication  
4.6.10 
Discontinuation of study treatment and premature patient withdrawal 
The planned duration of the study is 16  weeks (+/- 2 weeks) and patients should be followed until 
the end of the study except if any of the following conditions for early termination are met:  
 
Voluntary discontinuation (withdrawal of consent to collect or use their data)  


Novartis 
Confidential 
Page 17 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
Treatment discontinuation (patient no longer take the medication under observation)  
 
Addition of second AD treatment (patient no longer on monotherapy)  
 
All data generated up to the time of voluntary discontinuation (withdrawal of consent) and the 
reason(s) for discontinuation will be recorded. Patients who choose to withdraw consent will no 
longer be contacted for follow up information.  
 
Patients who discontinue treatment or patients who are no longer on monotherapy should be asked 
to return for an early discontinuation assessment. For patients who are lost to follow-up (i.e. those 
patients whose status is unclear because they fail to appear for study visits without stating an 
intention to withdraw), the physician should show "due diligence" by contacting the patients and 
asking them to return for a final assessment. Every effort should be made to obtain reason for 
discontinuation. The physician should document in the source documents steps taken to contact 
the patient, e.g. dates of telephone calls, registered letters, etc. 
4.6.11 
Emergency breaking of treatment assignment 
Not applicable  
4.6.12 
Study completion and post-study treatment 
Study completion for an individual patient will be 16 weeks. At the end of study, patient would 
continue to receive treatment as per the discretion of Investigator. 
4.6.13 
Early study termination 
The study can be terminated at any time for any reason by Novartis. Should this be necessary, 
the patient should be seen as soon as possible and treated for a prematurely withdrawn patient. 
The investigator may be informed of additional procedures to be followed in order to ensure 
that adequate consideration is given to the protection of the patient’s interests. The 
investigator will be responsible for informing IRBs and/or ECs of the early termination of the 
trial. 
5 
Visit schedule and assessments 
 
Error! Reference source not found. lists all of the assessments and indicates with an “x” 
when the visits are performed. 
 


Novartis 
Confidential 
Page 18 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
EOS = End of Study 
X = Assessment to be recorded on CRF 
*Physical examination includes examination of general appearance, skin, neck (including thyroid), eyes (excluding fundus), 
ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, and extremities. In addition, a neurological exam consisting of 
cranial nerve, motor and sensory assessments as performed in routine clinical practice. It also includes recording of pulse 
and blood pressure as per routine clinical care. 
** Height is assessed only at Visit 1 
At a minimum, patients will be contacted for safety evaluations during the 30 days following 
the last study visit or following the last administration of study treatment), including a final 
contact at the 30-day point. Documentation of attempts to contact the patient should be 
recorded in the source documentation.  
 
Examination 
Baseline Visit 
1 
(Day 1) 
Visit-2 
(8 ± 2 
weeks) 
EOS Visit 3 
(16 ± 2 
weeks) 
Informed consent 
X 
 
 
Patient demographics (sex, age, etc) 
X 
 
 
Relevant medical history 
X 
 
 
Vitals  
X 
X 
X 
Physical examination*  
X 
X 
X 
Height** and weight 
X 
X 
X 
Inclusion/Exclusion criteria 
X 
 
 
MMSE score 
X 
X 
X 
ADCS-ADL SIV score 
X 
 
X 
Concomitant medications  
 
X 
X 
Treatment for AD 
X 
X 
X 
Urine examination 
X 
X 
X 
Skin irritation assessment 
 
X 
X 
Patch adhesion assessment 
 
X 
X 
Adverse Events (AEs)and Serious Adverse Events (SAEs) 
recording 
X 
X 
X 
Compliance assessment using caregiver questionnaire 
 
X 
X 
EOS 
 
 
X 


Novartis 
Confidential 
Page 19 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
5.1 
Information to be collected on screening failures 
For all patients who have signed informed consent and are entered into the next epoch of the 
study will have all adverse events occurring after informed consent is signed recorded on 
the Adverse Event CRF. 
Investigators will have the discretion to record abnormal test findings on the medical history 
CRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature. 
5.2 
Patient demographics/other baseline characteristics 
 Date of birth or age and gender 
 Relevant Medical history  
At subsequent visits throughout the observation period, the following information will be 
updated: 
 Change in concomitant medications 
 Treatment taken for  AD 
 Physical examination which includes examination of general appearance, skin, neck 
(including thyroid), eyes (excluding fundus), ears, nose, throat, lungs, heart, abdomen, 
back, lymph nodes, and extremities. In addition, a neurological exam consisting of 
cranial nerve, motor and sensory assessments as performed in routine clinical 
practice.It also includes recording of pulse and blood pressure as per routine clinical 
care 
 Mini-Mental State Examination (MMSE) 
 ADCS-ADL SIV score 
5.3 
Treatment exposure and compliance 
 
Study drug patch administered during the course of the study will be recorded on the 
corresponding Dosage Administration Record CRF 
Other drugs administered prior to and continuing at start of study medication will be entered 
on the ‘Concomitant medications/significant non-drug therapies prior to the start of study’ 
CRF. 
Compliance will be assessed by the investigator and/or study personnel at each visit using 
information provided by the patient. This information should be captured in the source 
document at each visit 
 
5.4 
Efficacy 
5.4.1 
Efficacy assessment  
Mini-Mental State Examination (MMSE):  
Assessing the changes in Mini-Mental State Examination (MMSE): The MMSE is a brief, 
practical screening test for cognitive dysfunction (Folstein et al. 1975). The test consists of 


Novartis 
Confidential 
Page 20 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
five sections (orientation, registration, attention-calculation, recall, and language & Praxis) 
and results in a total possible score of 30, with higher scores indicating better function. 
MMSE shall be recorded at the start and at each visit as mentioned in table 5.1as a part of 
routine clinical practice.  
ADCS-ADL SIV score*: 
This is a tool to assess the ability of patients with moderate to severe dementia to perform 
activities of daily living.  ADCS-ADL SIV score is done at start and end of visit. This 
includes 19 questions and total score is 54. Administration instructions and Instruction card 
for the rater to use when administering the scale is separately provided  
 
*“Used with permission from the NIA Alzheimer’s Disease Cooperative Study (NIA Grant AG10483)”. 
5.4.2 
Appropriateness of efficacy assessments  
MMSE and ADCS-ADL SIV score is standard assessment tool for cognitive examination 
5.5 
Safety 
5.5.1 
Physical examination 
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular and neurological. If indicated based on medical history and/or 
symptoms, rectal, external genitalia, breast, and pelvic exams will be performed. 
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to signing informed consent must be 
included in the Medical History part of the CRF. Significant findings made after signing the 
informed consent which meet the definition of an Adverse Event must be recorded on the 
Adverse Event section of the CRF. 
5.5.2 
Dermatology examination:  
The following score system will be used to assess skin irritation: 
I. Dermal response: 
0 = No erythema (normal skin) 
1 = Erythema barely visible 
2 = Mild erythema 
3 = Moderate erythema 
4 = Severe erythema 
5 = Severe erythema with vesicles or blisters 
II. Other effects: 
O : Edema 
P : Papules (many small, red, solid, elevated lesions, surface of reaction with granular feeling) 
V : Small vesicles (< 0.5 cm) circumscribed elevations with visible fluid 
B : Large blister (> 0.5 cm) circumscribed elevations with visible fluid 


Novartis 
Confidential 
Page 21 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
Pu : Pustules (inflammatory small elevations containing purulent exudate) 
H : Hyperpigmentation (increase of the usual pigmentation limited to the patch test area) 
W : Weeping or oozing (may be a sign of vesiculation or blistering manifested by crusting) 
S : Extension of the reaction beyond patch-test site (on skin area where no test product was 
applied) 
A : Marked reaction to adhesive patch 
5.5.3 
Vital signs 
5.5.4 
Vital signs include Body temperature, BP and pulse and respiratory 
rate measurements. Height and weight 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram [kg] in indoor 
clothing, but without shoes) will be measured. 
5.5.5 
Patch adhesion assessment: 
 
For the patients randomized to the Exelon® patch treatment, patch adhesion to the skin will 
be evaluated by the caregiver. An estimate of the patch adherence will be provided and graded 
according to the patch adhesiveness score for the intervals between the scheduled outpatient 
visits. 
 
Following scores should be used to capture comments relating to patch adhesion: 
0 = 90 % adhered (essentially no lift off of the skin) 
1 = 75% to < 90% adhered (some edges only lifting off of the skin) 
2 = 50% to < 75% adhered (less than half of the patch lifting off the skin) 
3 = < 50% adhered but not detached (more than half the system lifting off of the skin without 
falling off) 
            4 = the patch was completely detached 
 
5.5.6 
Laboratory evaluations 
5.5.6.1 
Urinalysis 
 
Complete urine examination will be done at baseline,   visit 2 and end of study visit. 
5.5.7 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/patient population. 


Novartis 
Confidential 
Page 22 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
5.6 
Other assessments 
5.6.1 
Treatment and compliance:  
Caregiver medication questionnaire: Caregiver evaluation of the medications used for AD will 
be assessed using the Caregiver Medication Questionnaire (CMQ). The CMQ contains 4 
items, which focus on caregiver evaluation of medication administration and following 
schedule, and 2 global items asking about caregiver perceived compliance and satisfaction.. 
The CMQ questionnaire asks the caregiver to respond to the items based on the patch that the 
patient was taking during this study.  
 
5.6.2 
Health-related Quality of Life 
Not done  
5.6.3 
Pharmacokinetics 
Not done  
5.6.4 
Pharmacogenetics/pharmacogenomics 
Not done 
5.6.5 
Other biomarkers:  
Not done  
6 
Safety monitoring 
6.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The occurrence of adverse events should be sought by non-directive questioning of the patient 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the patient during or between visits or through physical examination, laboratory test, or 
other assessments. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
 they induce clinical signs or symptoms,  
 they are considered clinically significant,  
 they require therapy.  


Novartis 
Confidential 
Page 23 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying adverse events. Alert ranges for labs and other test abnormalities are 
included in Appendix 1. 
Adverse events should be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them accompanied by the following information. 
 the severity grade  
 mild: usually transient in nature and generally not interfering with normal activities 
 moderate: sufficiently discomforting to interfere with normal activities 
 severe: prevents normal activities 
 its relationship to the study treatment (no/yes), or 
its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved should be reported. 
 whether it constitutes a serious adverse event (SAE)  
 action taken regarding study treatment  
 whether other medication or therapies have been taken (concomitant medication/non-drug 
therapy) 
 its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 
An SAE is any adverse event (appearance of (or worsening of any pre-existing) undesirable 
sign(s), symptom(s) or medical conditions(s) which meets any one of the following criteria  
 is fatal or life-threatening  
 results in persistent or significant disability/incapacity 
 constitutes a congenital anomaly/birth defect 
 requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for  
 routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
 elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent  
 treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission  
 social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
 is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above. 


Novartis 
Confidential 
Page 24 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Unlike routine safety assessments, SAEs are monitored continuously and have special 
reporting requirements; see Section 7.2. 
All adverse events should be treated appropriately. Treatment may include one or more of the 
following: no action taken (i.e. further observation only); [study treatment/investigational] 
treatment dosage adjusted/temporarily interrupted; study drug(s) permanently discontinued; 
concomitant medication given; non-drug therapy given. The action taken to treat the adverse 
event should be recorded on the Adverse Event CRF.  
Once an adverse event is detected, it should be followed until its resolution or until it is 
judged to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the study treatment, the 
interventions required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the package insert. This information will be included in the patient informed consent 
and should be discussed with the patient during the study as needed. 
The investigator should also instruct each patient to report any new adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes 
might reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents, however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis. 
6.2 
Serious adverse event reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 30 days [after the last study visit/ following the last 
administration of study treatment if there are post-treatment follow-up visits with no required 
procedures] must be reported to Novartis within 24 hours of learning of its occurrence. Any 
SAEs experienced after the 30 days period should only be reported to Novartis if the 
investigator suspects a causal relationship to study treatment.  
Recurrent episodes, complications, or progression of the initial SAE must be reported as 
follow-up to the original episode, regardless of when the event occurs. This report must be 
submitted within 24 hours of the investigator receiving the follow-up information. An SAE 
that is considered completely unrelated to a previously reported one should be reported 
separately as a new event. 
Information about all SAEs (either initial or follow up information) is collected and recorded 
on the paper Serious Adverse Event Report Form. The investigator must assess the 
relationship to drug, complete the SAE Report Form in English, and send the completed, 
signed form by email/fax within 24 hours after awareness of the SAE to the local Novartis 
Patient Safety Department. The contact details of local Patient Safety are listed in the 
investigator folder provided to each site. The original copy of the SAE Report Form and 
acknowledgement must be kept with the case report form documentation at the study site. 
Follow-up information should be provided using a new paper SAE Report Form stating that 
this is a follow-up to a previously reported SAE 


Novartis 
Confidential 
Page 25 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
Follow- up information provided should describe whether the event has resolved or continues, 
if and how it was treated, whether the treatment code was broken or not and whether the 
patient continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs. 
If the SAE is not previously documented in the Package Insert (new occurrence) and is 
thought to be related to the investigational treatment, a Novartis Patient Safety Department 
associate may urgently require further information from the investigator for Health Authority 
reporting. Novartis may need to issue Biannual Suspected Unexpected Serious Adverse 
Reaction (SUSAR) Line listing to inform all investigators involved in any study with the same 
investigational treatment that this SAE has been reported. All SAE will be collected and 
reported to the competent authorities and relevant ethics committees in accordance with 
Directive 2001/20/EC or as per national regulatory requirements in participating countries. 
6.3 
Pregnancy reporting 
 
To ensure patient safety, each pregnancy occurring while the patient is on study treatment 
must be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy 
should be followed up to determine outcome, including spontaneous or voluntary termination, 
details of the birth, and the presence or absence of any birth defects, congenital abnormalities, 
or maternal and/or newborn complications. 
Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported by the 
investigator to the local Novartis Patient Safety Department. Pregnancy follow-up should be 
recorded on the same form and should include an assessment of the possible relationship to 
the study treatment. 
Any SAE experienced during pregnancy must be reported on the SAE Report Form.  
7 
Data review and database management 
7.1 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and CRFs with the investigators and their staff. During 
the study, the field monitor will visit the site regularly to check the completeness of patient 
records, the accuracy of entries on the CRFs, the adherence to the protocol and to Good 
Clinical Practice, the progress of enrollment, and to ensure that study. treatment is being 
stored, dispensed, and accounted for according to specifications. Key study personnel must be 
available to assist the field monitor during these visits. 
 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patient's file. [Data not requiring a separate written record will be defined before study start 


Novartis 
Confidential 
Page 26 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
and will be recorded directly on the CRFs.] The investigator must also keep the original 
informed consent form signed by the patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Novartis monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed. 
7.2 
Data collection 
Designated investigator staff must enter the information required by the protocol onto the 
Novartis CRFs that are printed on X [specify number of copies – i.e. 3-part]-part, non-carbon-
required paper. Field monitors will review the CRFs for completeness and accuracy and 
instruct site personnel to make any required corrections or additions. The CRFs are forwarded 
to the Medical Documents Reception Center of Novartis [or CRO working on behalf of 
Novartis] by field monitors or by the investigational site, with one copy being retained at the 
investigational site. Once the CRFs are received by Novartis [or CRO working on behalf of 
Novartis], their receipt is recorded, the original copy is placed in Central Files, and the non-
carbon-required copy is forwarded to the responsible Data Management staff for processing 
7.3 
Data Monitoring Committee 
Not required. 
7.4 
Adjudication Committee 
Not required. 
8 
Data analysis 
All analyses will be performed by Novartis or a designated CRO.  
Descriptive analyses will include n, mean, standard deviation, median, first quartile, third 
quartile and ranges for continuous variables and frequencies and percentages for categorical 
variables. Summaries will be presented together with estimates and corresponding 95% 
confidence intervals (CI) as appropriate 
8.1 
Analysis sets 
The intend to treat (IIT) set will include all patients having signed the Informed Consent, 
who have at least one post baseline assessment.  
The safety set will include all patients who provide Informed Consent to collect information 
and who were treated with at least one patch of rivastigmine 27 mg- 15 cm2 transdermal patch 
during this study,. Of note, the statement that a patient had no AE also constitutes a safety 
assessment. 


Novartis 
Confidential 
Page 27 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
All analyses will be carried out on the ITT set, while adverse event analyses will be conducted 
in the safety set.   
All patient demographics, medical history, prior treatments, and other baseline characteristics 
will be presented using standard descriptive statistics. Use of concomitant medication will be 
summarized using frequency counts and percentages by treatment group for patients in the 
Safety Set 
8.2 
Patient demographics and other baseline characteristics 
All patient demographics, medical history, prior treatments, and other baseline characteristics 
will be presented using standard descriptive statistics  
8.3 
Treatments 
Use of concomitant medication will be summarized using frequency counts and percentages 
by treatment group for patients in the Safety Set. 
8.4 
Analysis of the primary and key secondary variable(s) 
8.4.1 
Primary Variable 
8.4.2 
Statistical model, hypothesis, and method of analysis 
The primary variable analysis will be performed on the safety set.  No hypothesis is built for 
the study 
8.4.3 
Handling of missing values/censoring/discontinuations. 
  
LOCF (last observation carried forward) method will be used for missing values at week 16 
8.4.4 
Supportive analyses 
Not planned 
8.5 
Analysis of secondary variables 
8.5.1 
Efficacy variables 
The change from baseline in MMSE total score of 11 items will be summarized for the study. 
For Responses on the Caregiver Medication Questionnaire Mean scores will be computed for 
each of the other items in CMQ  
 
Change in the ADCS-Activities of Daily Living Inventory – Severe Impairment Version 
(ADCS-ADL SIV) Score will be summarized  for the study 
 


Novartis 
Confidential 
Page 28 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
8.5.2 
 Safety variables 
All safety analyses will be performed on the Safety Set. Adverse events (AEs) will be coded 
utilizing the MedDRA dictionary. AEs will be summarized by presenting the number and 
percentage of patients having any adverse event, having an adverse event in each body system 
and having each individual adverse event. For the safety analysis, all treatment emergent 
adverse events will be summarized and listed. The following treatment emergent adverse 
event summaries will be produced: overall by system organ class and preferred term, overall 
by system organ class, preferred term and maximum severity, suspected drug-related adverse 
events by system organ class and preferred term, serious adverse event by system organ class 
and preferred term, and adverse events leading to permanent discontinuation of study-
medication by system organ class and preferred term. Any other information collected (e.g. 
severity or relatedness to study medication) will also be summarized as appropriate. For each 
skin irritation scale, summary statistics will be provided by time and treatment group. When 
appropriate, two-sided 95%-confidence intervals for means and/or proportions as well as p-
values will be provided. The p-values will be used in a non-confirmatory manner. 
 
Further details will be outlined in the SAP 
8.5.3 
Resource utilization 
NA 
8.5.4 
Health-related Quality of Life 
8.5.5 
Pharmacokinetics 
8.5.6 
Pharmacogenetics/pharmacogenomics 
NA 
8.5.7 
Biomarkers 
NA 
8.5.8 
PK/PD 
NA 
8.6 
Interim analyses 
No interim analyses planned 
8.7 
Sample size calculation 
Incidence of adverse event data of ACTION study (74.60%) for Rivastigmine patch per day 
over a 24-week study period in patients with severe AD.  
Sample size is determined based on a precession approach considering normal approximation. 
A sample of 93 subjects will be able to estimate the incidence rate with an maximum error of 


Novartis 
Confidential 
Page 29 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
10% of the true population proportion with 90% of the cases. We assumed, the true 
population proportion is 0.746 (what is observed in US44) 
Similarly, a sample of 41 subjects will be able to estimate the incidence rate with an 
maximum error of 10% of the true population proportion with 85% of the cases and sample of 
23 subjects of the true population proportion with 80% of the cases. 
Considering drop out of 10% and true population proportion with 90%, 102 patients shall be 
enrolled. 
9 
Ethical considerations 
9.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 
21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid 
down in the Declaration of Helsinki. 
9.2 
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative of the patient. 
In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed 
consent document or a separate assent form. Informed consent must be obtained before 
conducting any study-specific procedures (i.e. all of the procedures described in the protocol). 
The process of obtaining informed consent should be documented in the patient source 
documents.  
Novartis will provide to investigators in a separate document a proposed informed consent 
form that complies with the ICH GCP guideline and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested by 
the investigator must be agreed to by Novartis before submission to the IRB/IEC, and a copy 
of the approved version must be provided to the Novartis monitor after IRB/IEC approval. 
Women of child bearing potential should be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 
9.3 
Responsibilities of the investigator and IRB/IEC 
The protocol and the proposed informed consent form must be reviewed and approved by a 
properly constituted Institutional Review Board/Independent Ethics Committee/Research 
Ethics Board (IRB/IEC) before study start. A signed and dated statement that the protocol and 


Novartis 
Confidential 
Page 30 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
informed consent have been approved by the IRB/IEC must be given to Novartis before study 
initiation. Prior to study start, the investigator is required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents and all 
of the instructions and procedures found in this protocol and to give access to all relevant data 
and records to Novartis monitors, auditors, Novartis Clinical Quality Assurance 
representatives, designated agents of Novartis, IRBs/IECs, and regulatory authorities as 
required. If an inspection of the clinical site is requested by a regulatory authority, the 
investigator must inform Novartis immediately that this request has been made. 
9.4 
Publication of study protocol and results 
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
10 
Protocol adherence 
Investigators ascertain they will apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact Novartis or its agents, if any, monitoring the 
trial to request approval of a protocol deviation, as requests to approve deviations will not be 
granted. 
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants.  Under no circumstances should an investigator collect additional data 
or conduct any additional procedures for any research related purpose involving any 
investigational drugs.  
If the investigator feels a protocol deviation would improve the conduct of the study this must 
be considered a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC it cannot be implemented. All significant protocol 
deviations will be recorded and reported in the CSR. 
10.1 
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC. Only 
amendments that are required for patient safety may be implemented prior to IRB/IEC 
approval. Notwithstanding the need for approval of formal protocol amendments, the 
investigator is expected to take any immediate action required for the safety of any patient 
included in this study, even if this action represents a deviation from the protocol. In such 
cases, Novartis should be notified of this action and the IRB/IEC at the study site should be 
informed within 10 working days or less, if required by local regulations. 
11 
References: 
1.Small GW. (1995) Alzheimer’s disease and other Dementing Disorders. In: Kaplan HI, Sadock BJ, (eds.) 
Comprehensive Textbook of Psychiatry/VI, volume 2, 6th ed; Maryland, Williams & Wilkins, p. 2562-2565.  
 


Novartis 
Confidential 
Page 31 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
2.Alzheimer’s Association (2008) 2008 Alzheimer’s Disease Facts and Figures, [online].Available from: 
http://www.alz.org/national/documents/report_alzfactsfigures2008.pdf 
3.Perry EK, Perry RH, Blessed G, et al. (1978) Changes in brain cholinesterases in senile dementia of Alzheimer 
type. Neuropath and Appl Neruobio, 4: 273-277.  
4. 
Kumar V, Calache M. (1991) Treatment of Alzheimer’s disease with cholinergic drugs. Int J of Clin 
Pharmacology, Therapy and Toxicology; 29(1): 23-37. 
5.   Knapp MJ, Knopman DS, Solomon PR, et al. (1994) A 30-Week randomized controlled trial of high-dose 
tacrine in patients with Alzheimer’s disease. JAMA; 271(13): 985-991.  
6. Rogers SL, Farlow MR, Doody RS, et al. (1998) A 24-week, double-blind, placebo-controlled trial of 
donepezil in patients with Alzheimer’s disease. Neurology, 50: 136-145 
7. Corey-Bloom J, Anand R, Veach J. (1998) A randomized trial evaluating the efficacy and safety of ENA 713 
(rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe 
Alzheimer’s disease. Int J Geriatr Psychopharm; 1: 55-65. 
8. Rosler M, Anand R, Cicin-Sain A, et al. (1999) Efficacy and safety of rivastigmine in patients with 
Alzheimer’s disease: international randomized controlled trial. BMJ, 318: 633-640. 
9. Raskind MA, Peskind ER, Wessel T, et al. (2000) Galantamine in AD, A 6-month randomized, placebo-
controlled trial with a 6-month extension. Neurology, 54: 2261-2268. 
10. Tariot PN, Solomon PR, Morris JC, et al. (2000) A 5-month, randomized placebo-controlled trial of 
galantamine in AD. Neurology, 54: 2269-2276. 
11. Reisberg B, Doody R, Stoffler A, et al. (2003) Memantine in moderate-to-severe Alzheimer’s disease. N 
Engl J Med, 348: 1333-1341. 
12. Van Dyck CH, Tariot PN, Meyers B, et al. (2007) A 24-week randomized, controlled trial of memantine in 
patients with moderate-to-severe Alzheimer’s disease. Alzheimer’s Dis Assoc Disord, 21: 136-143. 
13. Folstein, M., Folstein, S.E., McHugh, P.R. (1975). “Mini-Mental State” a Practical Method for Grading the 
Cognitive State of Patients for the Clinician. Journal of Psychiatric Research, 12(3); 189-198. 
14. Farlow M, Grossberg G, Sadowsky CH, Meng X, Somogyi M. (2013) A 24-Week, Randomized, Controlled 
Trial of Rivastigmine Patch 13.3 mg/24 h Versus 4.6 mg/24 h in Severe Alzheimer's Dementia. CNS 
Neuroscience & Therapeutics, 19(10): 745–752 
12 
Appendix 1– Caregiver Medication Questionnaire 
 
For each part of every question, please choose only one answer per row. Please mark your 
answers by placing an ‘X’ in the box or circling a number.  
Please answer all of the questions as honestly as you can and without help from anyone. There 
are no wrong answers. 
All of the information you provide will be kept confidential 


Novartis 
Confidential 
Page 32 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 


Novartis 
Confidential 
Page 33 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
 
 
 
 
 
 


Novartis 
Confidential 
Page 34 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
13 
Appendix 2: Patient Instructions for use and handling 
exelon patch 
Only one patch should be worn at a time. Remove the previous day’s Exelon Patch 
before applying a new one. Do not cut the patch into pieces. 
Where to apply Exelon Patch 
 
Before you apply Exelon Patch, make sure that your skin is: 
- 
clean, dry and hairless 
- 
free of any powder, oil, moisturiser, or lotion (that could keep the patch from sticking 
to your skin properly) 
- 
free of cuts, rashes and/or irritations. 
 
Every 24 hours, please gently remove any existing Exelon patch before putting on a 
new one. Having multiple patches on your body could expose you to an excessive 
amount of this medicine which could be potentially dangerous. 
 
Apply ONLY ONE patch per day to ONLY ONE of the following locations (shown in the 
figures below):  
o 
upper arm, left or right side, or  
o 
chest, left or right side, or 
o 
upper back, left or right side, or  
o 
lower back, left or right side,  
Avoid places where the patch can be rubbed off by tight clothing. 
 


Novartis 
Confidential 
Page 35 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
 
When changing your patch, you must remove the previous day’s patch before you apply your new 
patch to a different area of skin (for example on the right side of your body one day, then on the left 
side the next day). Do not apply a new patch to that same area for at least one week. 
How to apply Exelon Patch 
The patch is a thin, opaque, plastic patch that sticks to the skin. Each patch is sealed in a sachet that 
protects it until you are ready to put it on. Do not open the sachet or remove a patch until just before 
you apply it. 
Every 24 hours, please gently remove any existing Exelon patch before putting on a new one. 
Having multiple patches on your body could expose you to an excessive amount of this 
medicine which could be potentially dangerous. 
 
• 
Each patch is sealed in its own protective sachet.  
You should only open the sachet when you are ready to 
apply the patch. 
 
Tear or cut the sachet at the notch and remove the patch.  
 
• 
A protective liner covers the adhesive side of the patch.  
Peel off one side of the protective liner and do not touch 
the sticky part of the patch with the fingers. 
 
 
 
 
 
 
 
 
 
 
 
• 
Put the sticky side of the patch on the upper or lower 
back, upper arm or chest and then peel off the second 
side of the protective liner. 
 
 
• 
Then press the patch firmly in place for at least 30 
seconds using the palm of the hand to make sure that 
the edges stick well. 
 
 
 
 


Novartis 
Confidential 
Page 36 
Clinical Trial Protocol (Version No. 02) 
 
Protocol No. CENA713DIN01 
 
• 
If it helps you, you may write (e.g. the day of the week) on the Exelon Patch with a thin 
ball point pen. 
Exelon Patch should be worn continuously until it is time to replace it with a new patch. You may wish 
to experiment with different locations when applying a new patch, to find ones that are most 
comfortable for you and where clothing will not rub on the patch. 
How to remove Exelon Patch 
Gently pull at one edge of the Exelon Patch to remove it 
completely from the skin. 
 
In case the adhesive residue is left over on your skin, gently soak the area with warm water and 
mild soap or use baby oil to remove it. Alcohol or other dissolving liquids (nail polish remover or 
other solvents) should not be used. 
 
 
How to dispose Exelon Patch 
After the patch has been removed, fold it in half with the adhesive sides on the inside and press them 
together. Return the used patch to its original sachet and discard safely out of the reach and sight of 
children. Wash your hands with soap and water after removing the patch. In case of contact with eyes 
or if the eyes become red after handling the patch, rinse immediately with plenty of water and seek 
medical advice if symptoms do not resolve.  
Can you wear the patch when bathing, swimming, or in the sun? 
 
Bathing, swimming, or showering should not affect the patch. When swimming, you can wear 
the patch under your swimming costume. Make sure the patch does not loosen during these 
activities.  
 
The patch should not be exposed to any external heat sources (excessive sunlight, saunas, 
solarium) for long periods of time.  
What to do if Exelon Patch falls off 
If the patch falls off, a new patch should be applied for the rest of the day, then replace the patch the 
next day at the same time as usual. 
 

SAP_001.pdf: 
Official Title: 
A Prospective, 16 Week, Phase IV Study to Evaluate 
Safety, Tolerability and Effectiveness in Patients With 
Severe Dementia of the Alzheimer's Type Exposed to 
Rivastigmine (Exelon)15cm2 Transdermal Patch
NCT Number: 
Document Date: Statistical Analysis Plan (Version 1.0): 01-December-2022    
NCT02989402 


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
Statistical Analysis Plan 
PPD
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
1 
Table of Contents 
1 
Table of Contents ...................................................................................................................... 2 
2 
Signatures ................................................................................................................................. 5 
3 
Document History ...................................................................................................................... 6 
4 
Abbreviations ............................................................................................................................. 7 
5 
Introduction ................................................................................................................................ 8 
6 
Study Objective(s) ..................................................................................................................... 8 
6.1 
Primary Objective ............................................................................................................. 8 
6.2 
Secondary Objective(s)..................................................................................................... 8 
7 
Study Design ............................................................................................................................. 8 
7.1 
Overview ........................................................................................................................... 8 
7.1.1 
Study Design ............................................................................................................................. 8 
7.1.2 
Treatment Regimen ................................................................................................................... 9 
7.2 
Efficacy endpoints ........................................................................................................... 10 
7.3 
Safety Assessments ....................................................................................................... 10 
8 
General Statistical Considerations .......................................................................................... 10 
8.1 
Descriptive Statistics ....................................................................................................... 10 
8.2 
Analysis Population ........................................................................................................ 11 
8.3 
Definitions ....................................................................................................................... 11 
8.4 
Protocol Deviation ........................................................................................................... 12 
8.5 
Data Handling ................................................................................................................. 12 
8.5.1 
Imputation of Missing data ...................................................................................................... 12 
8.6 
Sample Size Calculation ................................................................................................. 13 
8.7 
Interim Analysis .............................................................................................................. 13 
8.8 
Statistical Software ......................................................................................................... 13 
9 
Statistical Analyses ................................................................................................................. 14 
9.1 
Patient Disposition .......................................................................................................... 14 
9.2 
Demographic Data and Baseline Characteristics ............................................................ 14 
9.3 
Medical History ............................................................................................................... 14 
9.4 
Prior and concomitant medication ................................................................................... 14 
9.5 
Treatment exposure ........................................................................................................ 15 
9.6 
Primary and Secondary Analysis .................................................................................... 15 
9.6.1 
Primary Analyses .................................................................................................................... 15 
9.6.2 
Secondary Analysis ................................................................................................................. 15 
9.7 
Safety Analysis ............................................................................................................... 16 
9.7.1 
Adverse Events ........................................................................................................................ 16 
9.7.2 
Physical Examination .............................................................................................................. 17 
9.7.3 
Vital Signs ............................................................................................................................... 17 
9.7.4 
Patch adhesion assessment ...................................................................................................... 17 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
9.7.5 
Urine examination ................................................................................................................... 18 
9.8 
Multicenter Studies ......................................................................................................... 18 
9.9 
Subgroup Analyses ......................................................................................................... 18 
10 
Deviation from the Study Protocol ...................................................................................... 18 
11 
Database Lock and Unblinding ........................................................................................... 18 
12 
References ......................................................................................................................... 18 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
STATISTICAL ANALYSIS PLAN 
Study Title: 
A prospective, 16 week, phase IV study to evaluate safety, tolerability 
and effectiveness in patients with severe dementia of the Alzheimer’s 
type exposed to rivastigmine (Exelon) 15 cm2 transdermal patch 
Sponsor Identification: 
CENA713DIN01 
Phase: 
Phase IV 
Sponsor Study Number: 
CENA713DIN01 
 
 
Responsible Biostatistician: 
 
Date of SAP: 
01 Dec 2022 
Version: 
Final 1.0 
Scope: 
Final 
PPD
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A
Client Confidential
Statistical Analysis Plan 
Sponsor: Novartis
Study Number:
Version: Final 1.0 Date: 01 Dec 2022
2
Signatures
Sponsor:
Novartis
Protocol No./
CENA713DIN01
Protocol Version No./Date:
Final Version 02 (Original protocol) / 21-Dec-2016
Study Title:
A prospective, 16-week, phase IV study to evaluate safety, tolerability and
effectiveness in patients with severe dementia of the Alzheimer’s type exposed to
rivastigmine (Exelon) 15 cm2 transdermal patch
CRF Version No./Date:
Version 2.0/03 Apr 2018
SAP Version No./Date:
Final 1.0/ 01 Dec 2022
T 
T 
GMT
Prepared By
01-Dec-2022 | 15:08 I
Date (DD-MMM-YYYY)
Reviewed By
01-Dec-2022 | 15:10 I
Date (DD-MMM-YYYY)
Approved By
01-Dec-2022 | 09:43
(Novartis)
Date (DD-MMM-YYYY)
PPD
PPD
PPD
PPD
PPD
PPD
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
3 
Document History 
 
Version 
Date 
Change to previous version 
Final 1.0 
01 Dec 2022 
Nil 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
4 
Abbreviations 
 
 
AE 
Adverse Event 
AD 
Alzheimer’s Disease 
BMI 
Body Mass Index 
Cm 
Centimeter 
CMQ 
Caregiver Medication Questionnaire 
CRF 
Case Report/Record Form 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
eCRF 
Electronic Case Report Form 
ENT 
Ears, Nose and Throat 
EOS 
End of Study 
ICH 
International Conference on Harmonization of Technical Requirements for Registration 
of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
ITT 
Intent to Treat 
IRB 
Institutional Review Board 
Kg 
Kilogram 
LOCF 
Last observation Carry Forward 
MMSE 
Mini-Mental State Examination 
NCS 
Non Clinically Significant 
 
 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
UTI 
Urinary Tract Infection 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
5 
Introduction 
This statistical analysis plan (SAP) provides the explicit guidance and describes the planned statistical and 
data handling methods to be followed during the final reporting and analyses. The intent of this document is 
to provide detailed information of the planned analysis of data related to safety and efficacy & to describe 
any applicable statistical procedures explicitly. It quotes the relevant statements directly from the protocol, 
for the applicable sections in this document (SAP). This SAP should be read in conjunction with the study 
protocol CENA713DIN01 version 02 (Original protocol) and dated 21-Dec-2016 and case report form (CRF) 
(version Final 2.0 dated 03 Apr 2018). 
6 
Study Objective(s) 
6.1 
Primary Objective 
The primary objective of the study is: 
1. To obtain safety data in patients with severe dementia of the Alzheimer’s type treated with 
rivastigmine 27 mg -15 cm2 transdermal patch for 16 weeks. 
6.2 
Secondary Objective(s) 
The secondary objective of the study is: 
1. To assess patient’s compliance of rivastigmine 27 mg -15 cm2 transdermal patch during 16 weeks 
treatment period 
2. To assess the skin tolerability (irritation and adhesion) during 16 weeks treatment period 
3. To assess the proportion of patients with UTI during 16 weeks treatment period 
4. To evaluate treatment effect by rivastigmine 27 mg -15 cm2 transdermal patch by assessing the 
changes in Mini-Mental State Examination (MMSE) 
5. To evaluate treatment efficacy by rivastigmine 27 mg -15 cm2 transdermal patch by assessing the 
changes in ADCS-Activities of Daily Living Inventory – Severe Impairment Version (ADCS-ADL 
SIV) Score. 
7 
Study Design 
7.1 
Overview 
 
7.1.1 
Study Design 
This is a multicenter, prospective, phase IV study evaluating safety, tolerability and effectiveness of 
rivastigmine 27 mg -15 cm2 transdermal patch prescribed in patients with severe dementia of the Alzheimer’s 
type as per discretion of treating physician. 
 
The prescription decision shall be independent of decision for inclusion in the study. Patients treated 
according to local routine clinical practice will be enrolled in the study upon signing an Informed Consent. 
Eligibility for study entry will be determined by the study investigator, in accordance with the selection 
criteria below. Signing of the Informed Consent defines the study entry visit. Routine urine examination shall 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
be done to detect any UTI. Compliance to treatment directions shall be reviewed by treating investigator at 
every visit. 
After 8 week and at 16 week, it is expected for the physician to follow up as per routine practice in India. 
The treating physician will assess the safety, tolerability and effectiveness of the rivastigmine 27 mg -15 cm2 
transdermal patch and may consider continuing or changing the therapy. 
Study Design Rationale 
This is open label study to examine the safety, effectiveness, and tolerability of the treatment in routine 
clinical practice, to determine how the treatment works under ordinary and variable conditions, prescribed 
by clinicians with varying degrees of expertise and practicing across the spectrum of health care settings, to 
treat a heterogeneous group of patients. 
The schedule of assessments will be as follows: 
 
Examination 
Baseline Visit 1 
(Day 1) 
Visit-2 
(8 ± 2 weeks) 
EOS Visit 3 
(16 ± 2 weeks) 
Informed consent 
X 
 
 
Patient demographics (sex, age, etc) 
X 
 
 
Relevant medical history 
X 
 
 
Vitals 
X 
X 
X 
Physical examination* 
X 
X 
X 
Height** and weight 
X 
X 
X 
Inclusion/Exclusion criteria 
X 
 
 
MMSE Score 
X 
X 
X 
ADCS-ADL SIV score 
X 
 
X 
Concomitant medications 
 
X 
X 
Treatment for AD 
X 
X 
X 
Urine examination 
X 
X 
X 
Skin irritation assessment 
 
X 
X 
Patch adhesion assessment 
 
X 
X 
Adverse Events (AEs)and Serious Adverse 
Events (SAEs) recording 
X 
X 
X 
Compliance assessment using caregiver 
questionnaire 
 
X 
X 
EOS 
 
 
X 
EOS = End of Study 
X = Assessment to be recorded on CRF 
*Physical examination includes examination of general appearance, skin, neck (including thyroid), eyes (excluding 
fundus), ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, and extremities. In addition, a neurological 
exam consisting of cranial nerve, motor and sensory assessments as performed in routine clinical practice. It also 
includes recording of pulse and blood pressure as per routine clinical care. 
** Height is assessed only at Visit 1 
 
 
7.1.2 
Treatment Regimen 
The study will include the following open-label drug: 
Exelon© patch: 15 cm2 patch sizes loaded with 27 mg of rivastigmine. 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
7.2 
Efficacy endpoints 
Efficacy endpoints will be as follows: 
 
1. 
Mini-Mental State Examination (MMSE): 
 
Assessing the changes in Mini-Mental State Examination (MMSE): The MMSE is a brief, practical 
screening test for cognitive dysfunction (Folstein et al. 1975). The test consists of five sections (orientation, 
registration, attention-calculation, recall, and language & Praxis) and results in a total possible score of 30, 
with higher scores indicating better function. MMSE shall be recorded at the start and at each visit. 
 
2. 
ADCS-ADL SIV SCORE: 
 
This is a tool to assess the ability of patients with moderate to severe dementia to perform activities of daily 
living. ADCS-ADL SIV score is done at start and end of visit. This includes 19 questions and total score 
is 54. Administration instructions and Instruction card for the rater to use when administering the scale is 
separately provided 
7.3 
Safety Assessments 
Safety endpoints will be as follows: 
 
x 
Urine examination 
x 
Skin reaction at patch 
x 
Patch adhesion 
x 
Adverse events. 
x 
Compliance by Caregiver medication questionnaire 
 
8 
General Statistical Considerations 
8.1 
Descriptive Statistics 
The following descriptive statistics will be calculated for continuous data and for ordered categorical data 
(ordinal data): 
 
Summary statistics are displayed with the following digits: 
 
Description 
Characteristic 
Number of decimal places 
Count 
n 
0 
Count corresponding to the number of patients for a group 
N 
0 
Mean 
Mean 
As in source + 1 
Standard Deviation 
SD 
Mean+1 
Minimum 
Min 
As in source 
Median 
Median 
As in source + 1 
Maximum 
Max 
As in source 
1st Quartile / 3rd Quartile 
Q1/Q3 
As in source + 1 
Percentage relative to N # 
% 
1 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
# Number of decimal places can be more than one, if necessary. All table percentages should be rounded to 
one decimal place if not stated otherwise. 
 
All data will be presented in the patient data listings. 
 
 
If either table or listing does not include any observation, then the following placeholder will be used: “NO 
DATA CONTRIBUTED TO THIS TABLE / LISTING”. 
 
8.2 
Analysis Population 
Two population will be considered for the analysis: The intend to treat (ITT) population and safety 
population. Analysis for all efficacy endpoints using the ITT population will be the primary approach for 
analysis. For safety endpoints, safety population will be used for analysis. 
 
 
Analysis Population 
Definition 
Screened Population 
All the subjects who screened in the study will be considered 
Intend to treat Population 
The intend to treat (ITT) set will include all patients having signed the Informed 
Consent, who have at least one post baseline assessment. 
Safety population 
The safety set will include all patients who provide Informed Consent to collect 
information and who were treated with at least one patch of rivastigmine 27 mg- 15 
cm2 transdermal patch during this study. Of note, the statement that a patient had no 
AE also constitutes a safety assessment 
 
8.3 
Definitions 
In the following table, the definitions and calculation of derived variables are summarized 
 
Variable / Term 
Definition / Way of calculation 
Age 
Int ((informed consent date – Birth date +1)/365.25) 
Baseline 
The last valid value prior to the first dose of study treatment 
BMI (kg/m2) 
Weight (kg) / (Height (m) x Height (m)) 
Duration of exposure 
Treatment end date- treatment start date + 1 
Treatment Start Date 
Date of dose administration on Day 1 in Investigational Product Log in the CRF 
Treatment End Date 
The last date from the ‘Investigational Product Log’ form to be considered as 
treatment end date 
Treatment Emergent AE (TEAE) 
An AE will be considered as treatment-emergent if the time of onset is on or after 
the time of the first dose or any AE that exist prior to first dose and if it increased 
in severity during the study. 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
8.4 
Protocol Deviation 
The relevant protocol deviations have to be defined by a systematic data review prior to database closure. 
For this purpose, protocol violations that occurred during the study such as violations of inclusion/exclusion 
criteria or forbidden concomitant medications or patient non-compliance will be assessed as ‘major’ or 
‘minor’ depending on their potential to interfere with the objectives of the study. Listings will be prepared to 
show the eligibility of all patients. Comprehensive justification for the classification of a protocol 
violation/deviation as “major” will be given in the integrated clinical study report. 
 
The protocol deviations (Major and Minor) will be summarized using frequency count and percentage and 
overall, using ITT Population. 
 
The list of protocol deviations will be reviewed by the sponsor and finalized before locking the database. 
 
8.5 
Data Handling 
 
8.5.1 
Imputation of Missing data 
LOCF (last observation carried forward) method will be used for missing values at week 16. 
Safety 
No imputation will be done on missing safety data, unless for partially incomplete dates for remote events 
such as AE, concomitant medication etc. 
 
For partial start dates: 
1. If the year is unknown, then do not impute the date but assign a missing value. 
2. If the month is unknown, then: 
a. If the year matches the year of the dose date, then impute the month and day of the dose date. 
3. If the day is unknown, then: 
a.  If the month and year match the month and year of the first dose date, then impute the day of the 
dose date. 
 
For partial end dates: 
1. If the year is unknown, then do not impute the date but assign a missing value. 
2. If the month is unknown, then do not impute the date and mark as ongoing for AE and Concomitant 
medication. 
3. If the day is unknown, then assign the last day of the month. 
 
After implementing the rules above, to determine whether AEs (or medications) with missing start or stop 
dates are pretreatment or on/after treatment, the following strategy will be used: 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
1. If the start date and stop date are both missing, then the most conservative approach is taken and the AE 
(or medication) is considered to be treatment-emergent (or concomitant medication). 
 
2. If the start date is missing but the stop date is not missing and is on or after the day of first study dose 
administration, then the most conservative approach is taken and the AE (or medication) is considered to be 
treatment-emergent (or concomitant medication). 
 
3. If the start date is missing but the stop date is not missing and is before the day of first study dose and after 
the date of signed informed consent, then the AE (or medication) is considered to be before treatment (or 
prior medication). 
 
4. If the start date is not missing but the stop date is missing, then the most conservative approach is taken, 
and medication is considered to be concomitant while the AE is defined by the start date. 
If the adverse event relationship flag is missing, the relationship for the adverse event will be imputed and 
will be considered as possibly related. If the Adverse Event Severity flag is missing, the severity will be 
imputed with the maximum severity as “Severe” and if the adverse event is flagged as Serious adverse event 
and the severity flag is missing then the maximum severity imputed will be “life-threatening” 
8.6 
Sample Size Calculation 
Incidence of adverse event data of ACTION study (74.60%) for Rivastigmine patch per day over a 24-week 
study period in patients with severe AD. 
The sample size is determined based on a precession approach considering normal approximation. A sample 
of 93 subjects will be able to estimate the incidence rate with a maximum error of 10% of the true population 
proportion with 90% of the cases. We assumed that the true population proportion is 0.746 (what is observed 
in US44) 
Similarly, a sample of 41 subjects will be able to estimate the incidence rate with a maximum error of 10% 
of the true population proportion with 85% of the cases and sample of 23 subjects of the true population 
proportion with 80% of the cases. 
Considering the drop out of 10% and the true population proportion with 90%, 102 patients shall be enrolled. 
 
8.7 
Interim Analysis 
No interim analyses are planned. 
 
8.8 
Statistical Software 
All statistical analyses will be performed with SAS®, Version 9.4 or later. 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
9 
Statistical Analyses 
9.1 
Patient Disposition 
Patient disposition will be tabulated with number and percentages of patient’s enrolled, dosed, completed the 
study according to the protocol or discontinued the study prematurely. The patients who prematurely 
discontinued the study and the reasons for their discontinuation will be presented. The disposition table will 
be summarized using “screened population”. 
 
 
9.2 
Demographic Data and Baseline Characteristics 
x 
Age (year) 
x 
Gender 
x 
Height (cm) 
x 
Weight (kg) 
x 
BMI((kg/m2) 
x 
Baseline MMSE Total Score 
x 
Baseline ADCS-ADL SIV Total score 
x 
Diagnosed with AD 
 
9.3 
Medical History 
All general medical history including complete review of all current and past conditions will be coded using 
MedDRA version 20.1. General medical history conditions will be summarized by system organ class, 
preferred term using SAF population. The version of the utilized dictionary will be presented as part of the 
provided tables and listings. Listing of medical history will be provided. 
 
Patients will be counted only once at the preferred term (PT), only once at the system organ class (SOC), and 
only once at patient level for the counting of total number of patients with a medical history term. Listings 
of medical history events for patients in the safety population will be provided. 
9.4 
Prior and concomitant medication 
Prior and concomitant medications will be assessed at screening and at each subsequent study visit. 
Medications will be coded using WHODDE+ HD DEC 2017 and will be summarized by ATC class (the 
highest available level), preferred name for the safety population. Patients taking the same medication 
multiple times will be counted once per medication. 
 
Medication will be classified as prior, If the medication that start and stop prior to the date of received study 
medication. Medications that are ongoing or ended after the first use of the study medication will be classified 
as concomitant. If the end date of the medication is unknown, it will also be considered as concomitant. 
Handling of missing date explained in section (Imputation of missing data section 8.5.1). 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
Listings will be presented for prior and concomitant medications. 
 
9.5 
Treatment exposure 
Study drug patch administered during the course of the study will be recorded on the corresponding Dosage 
Administration Record CRF 
Duration of treatment exposure will be summarized descriptively using safety population by visit. 
 
9.6 
Primary and Secondary Analysis 
 
9.6.1 
Primary Analyses 
 
x 
To obtain safety data in patients with severe dementia of the Alzheimer’s type treated with 
rivastigmine 27mg -15 cm2 transdermal patch for 16 weeks. 
 
The primary safety objective of this study will be assessed by collecting adverse events. Adverse 
events will be analysed using SAF Population. 
 
9.6.2 
Secondary Analysis 
 
1) To assess patient’s compliance of rivastigmine 27 mg -15 cm2 transdermal patch during 16 weeks 
treatment period 
The Compliance by Caregiver medication questionnaire will be summarized descriptively by visit 
using ITT population. 
 
2) To assess the skin tolerability (irritation and adhesion) during 16 weeks treatment period 
Skin tolerability will be summarized by the number and percentages of patients using safety 
population. 
 
3) To assess the proportion of patients with UTI during 16 weeks treatment period 
 
Proportion of patients with UTI will be summarized by the number and percentages of patients using 
safety population. 
 
4) To evaluate treatment effect by rivastigmine 27 mg -15 cm2 transdermal patch by assessing the 
changes in Mini-Mental State Examination (MMSE) 
 
The change from baseline for Week 8 and Week 16 in MMSE total score will be summarized 
descriptively using the ITT population and treatment for the study 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
5) To evaluate treatment efficacy by rivastigmine 27 mg -15 cm2 transdermal patch by assessing the 
changes in ADCS-Activities of Daily Living Inventory – Severe Impairment Version (ADCS-ADL 
SIV) Score 
 
The change from baseline in ADCS-ADL SIV score will be summarized descriptively and scores 
will also be presented by frequencies and percentages using the ITT population and treatment for 
the study. 
9.7 
Safety Analysis 
9.7.1 
Adverse Events 
Adverse Events will be coded using the Medical Dictionary of Regulatory Activities (MedDRA version 
20.1), the coded terms will be used for summarizing the AE(s). Only treatment emergent adverse events 
(TEAE) will be summarized in tables, while all events will be listed. Adverse events will be analyzed using 
safety population. 
 
An AE will be considered as treatment-emergent if the time of onset is on or after the time of the first dose 
or any AE that exist prior to first dose and if it increased in severity during the study period. Handling of 
missing data for AE are explained in section 8.5.1 (Imputation of missing data). 
 
An overall summary table which summarizes, the number and percentages of patients with adverse events, 
serious adverse events, adverse events leading to death, adverse events related to study drug and adverse 
events by severity categories will be provided. All the AE tables will be summarized based on TEAE, 
 
Patients experiencing any treatment emerging adverse events will be summarized by Preferred Term (PT) 
and SOC. The number and percentage of patients with at least one TEAE, SAE, discontinuation of study 
treatment due to death and TEAEs of severe intensity will be summarized by system organ class, preferred. 
Furthermore, listings of AEs, SAEs and Deaths will be provided. 
 
Furthermore, an overall Adverse event listing will be provided, and a separate listing will be provided for 
AE leading to death. 
 
AEs tables by primary system organ class and preferred term will be sorted in descending order of counts. 
 
 
Also an overall AE summary table which summarizes, the number and percentages of patients with adverse 
events, serious adverse events, permanently discontinued study treatment, adverse events leading to death, 
adverse events related to study drug and adverse events by severity categories will be provided for the SAF 
population. 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
A patient experiencing the same AE multiple times will be counted only once for that preferred term. 
Similarly, if a patient experiences multiple AEs within the same system organ class that patient will be 
counted only once in that system organ class. Maximum severity will be considered if a patient has multiple 
severity reported for same AE. In summaries by relationship, if a patient has the same AE on multiple 
occasions, the closest relationship to study drug, will be used for summary. 
 
9.7.2 
Physical Examination 
 
Physical examination will be performed at Baseline Visit 1(Day 1), Visit-2 (8 ± 2 weeks), EOS Visit 3 (16 ± 
2 weeks). Physical examination will include an examination of general appearance, skin, neck (including 
thyroid), eyes (Excluding fundus ), ENT, lungs, heart, abdomen, back, lymph nodes, extremities, Cranial 
nerve, Motor assessment, Sensory assessment, Rectal, External Genitalia, Breast and Pelvic Exams. 
 
Physical examination results will be summarized by number and percentages using SAF population. Listing 
will be provided for the Physical Examination. 
 
9.7.3 
Vital Signs 
Vital signs will be measured at baseline Visit 1(Day 1), Visit2 (8 ± 2 weeks) , EOS Visit 3 (16 ± 2 weeks) 
The vital signs parameters include: 
• 
Systolic Blood Pressure (mmHg) 
• 
Diastolic Blood Pressure (mmHg) 
• 
Pulse Rate (bpm) 
• 
Respiratory Rate (brpm) 
• 
Temperature (°F) 
• 
Height (centimeters) 
• 
Body weight (kg) 
 
The actual and change from baseline vital signs parameters will be summarized descriptively by visits. 
In addition, number and percentage of patients reaching ‘Normal’, ‘Abnormal CS’ and ‘Abnormal NCS’ 
results for Clinical significance will be summarized by visits. Data listings will be presented for vital signs 
parameters using SAF population. 
 
9.7.4 
Patch adhesion assessment 
Patch adhesion assessment will be measured at Visit-2 (8 ± 2 weeks), EOS Visit 3 (16 ± 2 weeks). 
A summary of these findings will be presented by number and percentages of patients using SAF population. 
Data listings will be presented for Patch adhesion assessment. 
PPD


DocuSign Envelope ID: 560AFEA3-F8B9-47B9-9608-839E19CE211A 
Client Confidential 
 
 
 
Statistical Analysis Plan 
Sponsor: Novartis 
Study Number:
 
Version: Final 1.0 Date: 01 Dec 2022 
 
9.7.5 
Urine examination 
Urine examination will be measured at Baseline Visit 1(Day 1), Visit-2 (8 ± 2 weeks), EOS Visit 3 (16 ± 2 
weeks. 
A summary of these findings will be presented by number and percentages of patients using SAF population 
 
9.8 
Multicenter Studies 
Yes. 
 
9.9 
Subgroup Analyses 
Not Applicable 
 
10 Deviation from the Study Protocol 
The following are the deviation from the study protocol. 
 
 
S.No 
Topic 
Protocol 
Changes from the protocol 
1 
Screened 
Population 
NA 
Screened population has been added in the 
analysis set in order to provide the 
information   regarding   the   patient 
disposition. 
2 
Analysis 
Population 
All analyses will be carried out on 
the ITT set, while adverse event 
analyses will be conducted in the 
safety set 
Analysis for all efficacy endpoints using 
the ITT population will be the primary 
approach for analysis. For safety endpoints, 
safety population will be used for analysis. 
 
11 Database Lock and Unblinding 
The SAP will be finalized prior to database lock. After the data cleaning process is finalized according to the 
data management plan (DMP) and the assignment of patients to the analysis sets is agreed and signed by the 
sponsor, the study database will be locked. Since the study is open label unblinding is not applicable. 
 
12 References 
Nil 
PPD


Official Title: 
A Prospective, 16 Week, Phase IV Study to Evaluate 
Safety, Tolerability and Effectiveness in Patients With 
Severe Dementia of the Alzheimer's Type Exposed to 
Rivastigmine (Exelon)15cm2 Transdermal Patch
NCT Number: 
Document Date: Catalogue of Tables, Listings and Figures (Version 1.0): 01-December-2022    
NCT02989402 


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
Page 1 of 63 
Catalogue of Tables, Listings and Figures 
Sponsor: 
Novartis 
Protocol No
CENA713DIN01
 
Protocol Version No./Date 
Final 2.0/ 21 Dec 2016 
Study Title 
A prospective, 16-week, phase IV study to evaluate safety, tolerability and 
effectiveness in patients with severe dementia of the Alzheimer’s type exposed to 
rivastigmine (Exelon) 15 cm2 transdermal patch. 
SAP Version No./Date: 
Final 1.0 / 01 Dec 2022 
PPD
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 2 of 63 
 
 
 
Table of Contents 
 
Introduction.............................................................................................................................................. 3 
General Statistical Considerations .......................................................................................................... 3 
List of Tables ........................................................................................................................................... 4 
List of Figures .......................................................................................................................................... 5 
List of Patient Data Listings..................................................................................................................... 5 
Mockups of Tables, Figures and patient data listings ............................................................................. 7 
 
Tables ...................................................................................................................................... 8 
 
Figures .................................................................................................................................. 42 
 
Patient Data Listings ............................................................................................................. 43 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 3 of 63 
 
 
Introduction 
This catalog includes examples of tables, figures and listings to support the analysis of a Statistical Analysis Plan 
(SAP).  
 
General Statistical Considerations  
All statistical analyses will be performed with SAS®, Version 9.4 or later. 
 
The following descriptive statistics will be calculated for continuous data and for ordered categorical data (ordinal 
data): 
Summary statistics are displayed with the following digits:  
Description 
Characteristic 
Number of 
decimal places 
Count 
n 
0 
Count corresponding to the number of patients for a group 
N 
0 
Mean 
Mean 
As in source + 1 
Standard Deviation 
SD 
Mean+1 
Minimum 
Min  
As in source 
Median 
Median 
As in source + 1 
Maximum 
Max 
As in source 
1st Quartile / 3rd Quartile 
Q1/Q3 
As in source + 1 
Percentage relative to N # 
% 
1 
# Number of decimal places can be two, if necessary. All table percentages should be rounded to one decimal 
place if not stated otherwise. 
The above-mentioned decimals are for informative purpose only and patient to change based on 
the study requirement. 
 
 
AEs Tables by primary system organ class and preferred term will be sorted alphabetically if not stated otherwise. 
All data will be presented in the patient data listings.  
If either table or listing does not include any observation, then the following placeholder will be used: “NO 
DATA CONTRIBUTED TO THIS TABLE / LISTING”. 
 
 
 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 4 of 63 
 
 
List of Tables 
Tables will be numbered within their section in ascending order. 
No. 
Table 
Population 
14.1 Patient Disposition 
TABLE 14.1.1 
Summary of Patient Disposition 
Screened population 
TABLE 14.1.2 
Number of Patients in Analysis Sets 
Screened population 
TABLE 14.1.3 
Number of Patients by Protocol Deviations 
Safety population 
TABLE 14.1.4 
Number of Patients at Each Visit 
Safety population 
TABLE 14.1.5 
Number of Patients Enrolled by Study Center 
Safety population 
TABLE 14.1.6 
Summary of Patient Demographic Data and Baseline Characteristics Safety population 
TABLE 14.1.7 
Summary of Medical History Classified by MedDRA by SOC and 
Preferred Term 
Safety Population 
TABLE 14.1.8 
Summary of Prior and Current Medications by ATC Class and 
Preferred Term 
Safety Population 
TABLE 14.1.9 
Summary of Concomitant Medication by ATC Class and Preferred 
Term 
Safety Population 
TABLE 14.1.10 
Summary of Treatment Exposure  
Safety Population 
14.2 Efficacy Analysis 
TABLE 14.2.1 
Summary of Mini-Mental State Examination 
ITT Population 
TABLE 14.2.2 
Summary of ADCS ADL-Severe Dementia Version 
ITT Population 
TABLE 14.2.2.1 
Summary and change from baseline of ADCS ADL-Severe Dementia 
Version total score 
ITT Population 
TABLE 14.2.3 
Summary of Responses on the Caregiver Medication Questionnaire  
ITT Population 
14.3 Safety Analysis 
TABLE 14.3.1 
Overall Summary of Adverse Events 
Safety Population 
TABLE 14.3.2 
Summary of Patients with Treatment Emergent Adverse Events 
Classified by System Organ Class, Preferred Term During the Study 
Safety Population 
TABLE 14.3.3 
Summary of Patients with Treatment Emergent Adverse Events 
Classified by System Organ Class, Preferred Term and Severity 
Safety Population 
TABLE 14.3.4 
Summary of Patients with Treatment Emergent Adverse Events 
Classified by System Organ Class, Preferred Term and Relation to 
study drug 
Safety Population 
TABLE 14.3.5 
Summary of Patients with Treatment Emergent Adverse Events 
Classified by System Organ Class, Preferred Term and Action 
Taken 
Safety Population 
TABLE 14.3.6 
Summary of Patients with Treatment Emergent Adverse Events 
Classified by System Organ Class, Preferred Term and Outcome 
Safety Population 
TABLE 14.3.7 
Number and Percentage of Patients with Serious Treatment 
Emergent Adverse Events Classified by System Organ Class and 
Preferred Term 
Safety Population 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 5 of 63 
 
 
No. 
Table 
Population 
TABLE 14.3.8 
Summary of Skin tolerability during 16 weeks treatment period 
Safety Population 
TABLE 14.3.9 
Summary of proportion of patients with UTI during 16 weeks 
treatment period 
Safety Population 
TABLE 14.3.10 
Summary and Change from Baseline of Lab parameters by Visit and 
Treatment 
Safety Population 
TABLE 14.3.11 
Summary of Overall Interpretation of Laboratory Parameters by 
Visit and Treatment 
Safety Population 
TABLE 14.3.12 
Summary of Actual and Change from Baseline for Vital Sign by 
Visit 
Safety Population 
TABLE 14.3.13 
Summary of Overall interpretation of Vital Signs by Visit 
Safety Population 
TABLE 14.3.14 
Summary of Overall Interpretation of Physical Examination by Visit Safety Population 
List of Figures 
Not Applicable 
List of Patient Data Listings 
 
In general, patient data listings should include all patients with data. 
 
A listing with all titles of patient data listings should be provided in accordance with the following structure 
No. 
Listing 
16.2.1.1  
Inclusion / Exclusion Criteria  
16.2.1.2 
Study Completion Details 
16.2.1.3  
Date of Visit  
16.2.2  
Protocol Deviations 
16.2.3  
Patients excluded from the analysis 
16.2.4.1  
Patient Demographic and Baseline Characteristics 
16.2.4.2 
Medical History  
16.2.4.3 
Prior and Current Medication 
16.2.4.4 
Concomitant Medication 
16.2.4.5.1 
Investigational Product Log 
16.2.4.5.2 
Treatment Exposure 
16.2.6  
Individual efficacy response data 
16.2.6.1  
Mini-Mental State Examination 
16.2.6.2  
Caregiver Medication Questionnaire 
16.2.6.3  
Patch Adhesion and Skin Reaction at Patch Site 
16.2.6.4 
ADCS ADL — Severe Dementia Version 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 6 of 63 
 
 
16.2.7.1  
Adverse Event by Patient 
16.2.7.1.1  
Serious Adverse Event by Patient 
16.2.8.1  
Lab Parameters – Urine Examination 
16.2.8.2 
Vital Signs 
16.2.8.3 
Physical Examination 
16.2.8.4 
Treatment of Alzheimer Disease 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 7 of 63 
 
 
Mockups of Tables, Figures and patient data listings 
Please note: Yellow resp. cursive texts are working advices. 
 
In General: 
• 
Required margins: at least 0.75 cm on the upper and lower margin and at least 1.0 cm on the left and right sides. All tables and listings will be landscape and centered 
format. All figures will be landscape and centered format, unless portrait orientation suggests that the information presented is easier to interpret. 
All output should have the following header at the upper left margin: 
 
<Sponsor> 
Protocol No.: <Protocol No.> 
and the following header at the upper right margin: 
<Draft/Final Version>,  ddmmmyyyy 
Page  n of N 
• Tables/appendices/listings should be internally paginated (i.e., page numbers should appear sequentially within each table). The name of the SAS program used to generate 
the output shall be displayed in the lower left corner. SAS Monospace, font size 8 will be used, although the mockup below would indicate differently. 
• Tables of Contents will be generated separately for Tables and Listings, listing numbers and titles. A file separate from Tables and Listings output must be produced. TOC 
pages will bear the standard header. 
Tables in general:  
• 
All necessary footnotes should be given to understand the values 
• 
Tables template should be as mentioned in SAP . 
•  Align numbers generally to decimal points (do not center numbers) 
 
Figures in general: 
• 
Figures should be made clear to interpret the data points plotted; 
• 
Appropriate legends should be placed to refer the plotted points 
 
Data Listings in general:    
• 
All Listings should be - paged by site and labeled with site number and sorted by investigation site, patient and actual date and time. 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 8 of 63 
 
 
 Tables 
Table 14.1.1: Patient Disposition 
Novartis  
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.1 
Summary of Patient Disposition 
 (Screened Population) 
Total 
n  (%) 
 
 
 
 
Number of patients screened  
xxx  
Number of patients screen failure 
xxx (xx.x) 
 
 
Reasons for screen failure: 
 
        Reason 1 
xx (xx.x) 
 ………….. 
…….. 
 
 
Number of patients enrolled 
xxx (xx.x) 
Number of patients dosed 
xxx (xx.x) 
 
 
Number of patients completed the study 
xx (xx.x) 
Number of patients withdrawn 
xx (xx.x) 
 
 
Reasons for withdrawn: 
 
        Reason 1 
xx (xx.x) 
        Reason 2 
xx (xx.x) 
 ………….. 
…….. 
  
n: Total number of patients in a given category  
Percentage for reasons of withdrawn was calculated based on the number of patients dosed 
Percentages are based on the total number of patients under screened patients 
Analysis Dataset: XXXX  
Source Listing: Listing xx.x.x 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 9 of 63 
 
 
 
Table 14.1.2: Number of Patients Included from Analysis Sets 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.2 
Number of Patients in Analysis Sets 
(Screened Population) 
 
Total 
(N = xxx) 
n (%) 
 
 
 
 
Safety (SAF) Population 
 
xx (xx.x) 
Intend to treat Population (ITT) 
 
xx (xx.x) 
 N: Total number of patients Screened 
n: Total number of patients in a given category  
Percentages are based on the total number of patient’s under safety population. 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 10 of 63 
 
 
Table 14.1.3: Number of Patients by Protocol Deviations  
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y 
Table 14.1.3 
Number of Patients by Protocol Deviations 
(Safety Population) 
Protocol Deviation 
Total 
(N=xx) 
n (%) 
Number of patients with any protocol deviations (Major/Minor) 
xx (xx.x) 
 
Major Protocol Deviations 
 
xx (xx.x) 
   Reason: 
           Deviation 1 
           Deviation 2 
           .............. 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Minor Protocol Deviations 
 
xx (xx.x) 
   Reason: 
           Deviation 1 
           Deviation 2 
           .............. 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
N = The total number of patients in the safety population  
n = Number of patients with non-missing data within the specific category. 
Percentages are based on the total number of patients in the safety population. 
A patient may record more than one reason for a major/minor deviation. All reasons will be counted in the table.  
Patients experiencing multiple deviation will be counted only once under the category of Major/Minor protocol deviations. 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 11 of 63 
 
 
Table 14.1.4: Number of Patients at Each Visit 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.4 
Number of Patients at Each Visit 
(Safety Population) 
Visit 
 
Total 
(N = xx) 
n (%) 
 
 
 
 
Baseline Visit 
xx 
(xx.x) 
Visit 2  
xx 
(xx.x) 
EOS 
xx 
(xx.x) 
 
 
 N: Total number of patients in the safety population 
n: Total number of patients in a given category  
Percentages are based on the total number of patients under safety Population  
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
  
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 12 of 63 
 
 
Table 14.1.5: Number of Patients Enrolled by Study Center 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.5 
Number of Patients Enrolled by Study Center 
(Safety Population) 
Center Number 
 
Total 
(N = xx) 
n (%) 
 
 
 
 
 
1 
 
xx (xx.x) 
2 
 
xx (xx.x) 
3 
 
xx (xx.x) 
4 
… 
 
xx (xx.x) 
……. 
 
 
 
 N: Total number of patients in the safety population 
n: Total number of patients in a given category  
Percentages are based on the total number of patients under safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 13 of 63 
 
 
Table 14.1.6: Summary of Patient Demographic Characteristics 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y y  
Table 14.1.6 
Summary of Patient Demographic Data and Baseline Characteristics 
(Safety Population) 
Variable 
  
Statistics  
 
Total 
(N = xxx) 
Age (Years) 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
 Max 
x.x 
 
 
 
Gender 
Female 
xx (xx.x) 
 
Male 
xx (xx.x) 
 
 
 
Height (cm) 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
 Max 
x.x 
 
 
 
Weight (kg) 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
 Max 
x.x 
 
 
 
BMI (kg/m2) 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
 Max 
x.x 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 14 of 63 
 
 
Variable 
  
Statistics  
 
Total 
(N = xxx) 
 
 
 
Baseline MMSE Total Score 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
 Max 
x.x 
 
 
 
Baseline ADCS-ADL SIV Total score 
 n 
xxx 
 
 Mean 
xx.x 
 
 SD 
xx.x 
 
 Min 
xx.x 
 
 Median 
xx.x 
 
Max 
x.x 
 
 
 
Patient diagnosed for AD 
Yes 
No 
xx (xx.x) 
xx (xx.x) 
 
 
 
 N: Total number of patients in the safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
  
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 15 of 63 
 
 
 
Table 14.1.7: Summary of Medical History Classified by MedDRA Preferred Term 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y 
Table 14.1.7 
Summary of Medical History Classified by MedDRA by SOC and Preferred Term 
(Safety Population) 
System Organ Class / 
   Preferred Term  
 
(N = xx) 
n  (%) 
 
 
 
Number of patients with atleast one condition  
 
xx (xx.x) 
 
System Organ Class  
 
 
xx (xx.x) 
 
Preferred Term 1 
 
xx (xx.x) 
          Preferred Term 2 
 
xx (xx.x) 
 
 
 
…………… 
 
……… 
 N: Total number of patients in the safety population 
n: Total number of patients in a given category  
Patients are counted only once within each SOC class and preferred term 
Medical History Terms are coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Percentages are based on the total number of patients under safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
  
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 16 of 63 
 
 
Table 14.1.8: Summary of Prior Medications by ATC Class and Preferred Term 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.8 
Summary of Prior and Current Medications by ATC Class and Preferred Term 
(Safety Population) 
ATC Class 
     Preferred Term 
 
 (N = xx) 
n (%) 
 
 
 
Number of patients with at least one medication recorded 
 
xx (xx.x) 
 
 
 
ATC level  
 
xx (xx.x) 
    Preferred Term 1 
 
xx (xx.x) 
    Preferred Term 2 
 
       xx (xx.x) 
………….. 
 
……… 
N = The total number of patients in the safety population 
n = Number of patients with non-missing data within the specific category. 
Percentages are based on the total number of patient’s under safety population 
Patients are counted only once within each ATC class and preferred term 
Prior and current medications are coded using WHODDE+ HD DEC 2017 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 17 of 63 
 
 
Table 14.1.9 
Summary of Concomitant Medication by ATC Class and Preferred Term 
 
 
 
 
 
 
 
 
(Safety Population) 
 
<Refer to table 14.1.8 for shell format> 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 18 of 63 
 
 
Table 14.1.10: Summary of Treatment Exposure  
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.1.10 
Summary of Treatment Exposure  
(Safety Population) 
Variable 
  
Statistics  
 
 
Total 
(N = xxx) 
Treatment Exposure  (days) 
 n 
 
xxx 
 
 Mean 
 
xx.x 
 
 SD 
 
xx.xx 
 
 Min 
 
xx.x 
 
 Median 
 
xx.x 
 
 Max 
 
x.x 
 
 
 
 
Total Number of patches dispensed 
 n 
 
xxx 
 
 Mean 
 
xx.x 
 
 SD 
 
xx.xx 
 
 Min 
 
xx.x 
 
 Median 
 
xx.x 
 
 Max 
 
x.x 
 
 
 
 
Total Number of patches Returned 
 n 
 
xxx 
 
 Mean 
 
xx.x 
 
 SD 
 
xx.xx 
 
 Min 
 
xx.x 
 
 Median 
 
xx.x 
 
 Max 
 
x.x 
 
 
 
 
 N: Total number of patient’s in the safety population 
 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
  
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 19 of 63 
 
 
Table 14.2.1: Summary of Mini-Mental State Examination 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.2.1 
Summary of Mini-Mental State Examination 
 (ITT Population) 
 
Parameter 
Visit 
Statistics 
Actual 
(N=xxx) 
Change from baseline 
(N=xxx) 
Orientation 
Baseline 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
Visit 2 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
EOS 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
Registration 
Baseline 
n 
Mean ± SD 
Q1 
xx 
xx.x ± xx.xx 
xx.x 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 20 of 63 
 
 
Parameter 
Visit 
Statistics 
Actual 
(N=xxx) 
Change from baseline 
(N=xxx) 
Median 
Q3 
(Min, Max) 
 
xx.x 
xx.x 
(xx.x , xx.x) 
 
Visit 2 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
 
EOS 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
 
…… 
 
 
 
 
……… 
 
 
 
…….. 
 
 
 
……….. 
 
 
 
………. 
Total 
Baseline 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
 
Visit 2 
n 
Mean ± SD 
xx 
xx.x ± xx.xx 
xx 
xx.x ± xx.xx 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 21 of 63 
 
 
Parameter 
Visit 
Statistics 
Actual 
(N=xxx) 
Change from baseline 
(N=xxx) 
Q1 
Median 
Q3 
(Min, Max) 
 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
EOS 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
 
N: Total number of patient’s in the ITT population 
n: Total number of patients in a given category 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
Programming note: 
 
This table will consists of five sections (orientation, registration, attention-calculation, recall, and language & Praxis) and Total  
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 22 of 63 
 
 
Table 14.2.2: Summary of ADCS ADL-Severe Dementia Version 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.2.2 
Summary of ADCS ADL-Severe Dementia Version 
 (ITT Population) 
ADCS ADL 
 (N=xx) 
 
 
 
 
n (%) 
Eating,, 
 
xx (xx.x) 
Walking 
 
xx (xx.x) 
Bowel and Bladder 
 
xx (xx.x) 
Bathing, 
 
xx (xx.x) 
Grooming, 
 
xx (xx.x) 
--- 
 
--- 
 
 
 
N: Total number of patient’s in the ITT population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 23 of 63 
 
 
Table 14.2.2.1: Summary and change from baseline of ADCS ADL-Severe Dementia Version total score 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.2.2.1 
Summary and change from baseline of ADCS ADL-Severe Dementia Version total score 
 (ITT Population) 
 
Visit 
Statistics 
Actual 
(N=xxx) 
Change from baseline 
(N=xxx) 
Baseline 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
Visit 2 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
EOS 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
EOS 
n 
Mean ± SD 
Q1 
Median 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 24 of 63 
 
 
Visit 
Statistics 
Actual 
(N=xxx) 
Change from baseline 
(N=xxx) 
Q3 
(Min, Max) 
xx.x 
(xx.x , xx.x) 
xx.x 
(xx.x , xx.x) 
 
N: Total number of patient’s in the ITT population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 25 of 63 
 
 
 
 
Table 14.2.3: Summary of Responses on the Caregiver Medication Questionnaire  
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.2.3 
Summary of Responses on the Caregiver Medication Questionnaire Mean scores 
 (ITT Population) 
Visit 
Parameter 
Category 
Statistics 
Total 
 (N=xx) 
n (%) 
Visit2 
During the past 1 week 
A patch ever skipped 
Never 
xx (xx.xx) 
 
 
 
1 day 
xx (xx.xx) 
 
 
 
2 days 
xx (xx.xx) 
 
 
 
3 days 
xx (xx.xx) 
 
 
 
4 or more days 
xx (xx.xx) 
 
 
 
 
 
 
 
The patch taken later than intended 
Never 
xx (xx.xx) 
 
 
 
1 day 
xx (xx.xx) 
 
 
 
2 days 
xx (xx.xx) 
 
 
 
3 days 
xx (xx.xx) 
 
 
 
4 or more days 
xx (xx.xx) 
 
 
 
 
 
 
 
 
 
 
 
Extent of agreement 
I was concerned that my patient missed taking his / her patch medication  
Always 
 
 
 
 
Most of the time 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 26 of 63 
 
 
Visit 
Parameter 
Category 
Statistics 
Total 
 (N=xx) 
n (%) 
 
 
 
Sometimes 
 
 
 
 
Rarely 
 
 
 
 
Never 
 
 
 
 
 
 
 
 
I found it difficult to remember to administer the patch medication 
Always 
 
 
 
 
Most of the time 
 
 
 
 
Sometimes 
 
 
 
 
Rarely 
 
 
 
 
Never 
 
 
 
 
 
 
 
Overall compliance 
 
n 
xx 
 
 
 
Mean ± SD 
xx.x ± xx.x 
 
 
 
Q1 
xx.x 
 
 
 
Median 
xx.x 
 
 
 
Q3 
xx.x 
 
 
 
(Min, Max) 
(xx.x , xx.x) 
 
 
 
 
 
 
 
 
n 
xx 
 
satisfied or dissatisfied 
 
Mean ± SD 
xx.x ± xx.x 
 
 
 
Q1 
xx.x 
 
 
 
Median 
xx.x 
 
 
 
Q3 
xx.x 
 
 
 
(Min, Max) 
(xx.x , xx.x) 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 27 of 63 
 
 
Visit 
Parameter 
Category 
Statistics 
Total 
 (N=xx) 
n (%) 
Visit3 
--- 
--- 
-- 
-- 
N: Total number of patient’s in the ITT population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
Programming note: 
 
This table will consist of mean scores of Visit-2 (8 + 2 weeks) and Visit-3 (16+ 2 weeks)  
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 28 of 63 
 
 
Table 14.3.1: Overall Summary of Adverse Events 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.1 
Overall Summary of Adverse Events  
(Safety Population) 
 
Total 
(N=xxx) 
n (%) E 
Adverse Events 
 
xx  (xx.x) xx 
Treatment Emergent Adverse Events 
xx  (xx.x) xx 
Serious Adverse Events  
 
xx  (xx.x) xx 
Adverse Event related to study drug 
 
xx  (xx.x) xx 
Adverse Events Leading to Study Medication Discontinuation  
 
xx  (xx.x) xx 
Adverse Events Leading to death 
          
xx  (xx.x) xx 
AE’s by maximum severity 
 
      Mild 
      Moderate 
      Severe 
             
 
 
xx  (xx.x) xx 
xx  (xx.x) xx 
xx  (xx.x) xx 
N = Total number of patients in the safety population 
n: number of patients with atleast one AE in the specified field. E: Number of Events 
This table includes only the treatment emergent adverse events 
Percentages are based on the total number of patient’s under Safety population 
Adverse Events will be coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 29 of 63 
 
 
Table 14.3.2: Summary of Patient’s with Adverse Events Classified by System Organ Class, Preferred Term During the Study 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.2 
Summary of Patient’s with Treatment Emergent Adverse Events Classified by System Organ Class, Preferred Term During the Study  
(Safety Population) 
System Organ Class 
      Preferred Term 
Total 
(N=xxx) 
n (%) E 
Number of patients with at least one AE 
xx  (xx.x) xx 
SOC1 
xx  (xx.x) xx 
      PT 1 
xx  (xx.x) xx 
             …. 
Xx  (xx.x) xx 
      
SOC2 
 
xx  (xx.x) xx 
      PT 1 
xx  (xx.x) xx 
      PT 2 
xx  (xx.x) xx 
….. 
….. 
       
N = Total number of patients in the safety population 
n: number of patients with atleast one AE in the specified fiel . E: Number of Events 
Patients are counted only once within each Preferred Term and System Organ Class 
Percentages are based on the total number of patient’s under Safety population 
Adverse Events will be coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
                    
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 30 of 63 
 
 
Table 14.3.3: Summary of Patients with Adverse Events Classified by System Organ Class, Preferred Term and Severity   
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.3 
Summary of Patients with Treatment Emergent Adverse Events Classified by System Organ Class, Preferred Term and Severity   
(Safety Population) 
 
System Organ Class 
     Preferred Term 
Severity 
Total 
(N=xxx) 
n (%) E 
Number of patients with at least one AE 
Mild 
Moderate 
Severe 
 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
  SOC 1 
          
      PT 1 
Mild 
Moderate 
Severe 
Mild 
Moderate 
Severe 
…..... 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
 
 ........ 
...... 
N = Total number of patients in the safety population 
n: number of patients with at least one AE in the specified field. E: Number of Events   
Percentages are based on the total number of patient’s under Safety population 
Adverse Events will be coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
  
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 31 of 63 
 
 
 
 
Table 14.3.4: Summary of Patients with Treatment Emergent Adverse Events Classified by System Organ Class, Preferred Term and Relation to study drug 
 
(Safety Population) 
 
<Refer to table 14.3.3 for shell format> 
 
 
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
 
Table 14.3.5: Summary of Patients with Treatment Emergent Adverse Events Classified by System Organ Class, Preferred Term and Action Taken 
 
(Safety Population) 
 
<Refer to table 14.3.3 for shell format> 
 
 
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
Table 14.3.6: Summary of Patients with Treatment Emergent Adverse Events Classified by System Organ Class, Preferred Term and Outcome 
 
(Safety Population) 
 
<Refer to table 14.3.3 for shell format> 
 
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 32 of 63 
 
 
Table 14.3.7: Number and Percentage of Patients with Treatment Emergent Serious Adverse Events Classified by System Organ Class and Preferred Term 
 
(Safety Population) 
 
<Refer to table 14.3.2 for shell format> 
 
 
Programming Note: 
Note 1: System organ class and preferred term are ordered alphabetically. 
Note 2: Patients are counted only once within each Preferred Term and System Organ Class 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: EA-CT-18-001 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 33 of 63 
 
 
Table 14.3.8: Summary of Skin tolerability during 16 weeks treatment period 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.8 
Summary of Skin tolerability during 16 weeks treatment period 
 (Safety Population) 
 
Visit 
Parameter 
Category 
Total 
(N=xx) 
 
 
 
n (%) 
Visit 2 
Score to capture comments relating to patch adhesion 
0 
1 
2 
3 
4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Has patch skin reaction occurred? 
Yes 
No 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Score to assess skin irritation (Dermal response) 
0 
1 
2 
3 
4 
5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Score to assess skin irritation (Other effects) 
Yes 
No 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Other effects 
O 
P 
xx (xx.x) 
xx (xx.x) 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 34 of 63 
 
 
V 
B 
Pu 
H 
W 
S 
A 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Visit 3 
…. 
…. 
…. 
                 N: Total number of patient’s in the safety population 
                Analysis Dataset: XXXX 
                Source Listing: Listing xx.x.x 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 35 of 63 
 
 
Table 14.3.9: Summary of proportion of patients with UTI during 16 weeks treatment period 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.9 
Summary of proportion of patients with UTI during 16 weeks treatment period 
 (Safety Population) 
 
Total 
(N=xx) 
 
n (%) 
Summary of patients with UTI 
xx (xx.x) 
 
 
N: Total number of patient’s in the safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 36 of 63 
 
 
Table 14.3.10: Summary and Change from Baseline of Lab parameters by Visit and Treatment 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.10 
Summary and Change from Baseline of Lab parameters by Visit and Treatment  
(Safety Population) 
Lab Category 
Parameters 
Visit 
Statistics* 
 
 
Actual 
Change from baseline 
Chemical 
Protein 
Baseline 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
 
Visit 2 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
……….. 
………. 
........ 
 
......... 
 
......... 
 
......... 
      
N = Total number of patients in the safety population 
Change from baseline = (Day X – baseline) 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
    Programming note: 
This table will consist of Physical (pH, Specific Gravity, Colour and Others), Chemical (Protein, Glucose, Ketones, Others) and Microscopy (Pus, RBC, Epithelial Cell, WBC 
and Others)      
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 37 of 63 
 
 
Table 14.3.11: Summary of Overall Interpretation of Laboratory Parameters by Visit and Treatment 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.11 
Summary of Overall Interpretation of Laboratory Parameters by Visit and Treatment 
(Safety Population) 
Lab Category 
Lab Test 
 Visit 
Categories 
 (N=xx) 
n (%) 
Chemical 
 Protein 
Baseline 
Normal 
xx (xx.x) 
Abnormal-NCS 
xx (xx.x) 
Abnormal-CS 
 
xx (xx.x) 
Visit 2 
Normal 
xx (xx.x) 
Abnormal-NCS 
xx (xx.x) 
Abnormal-CS 
 
xx (xx.x) 
… 
… 
… 
... 
... 
... 
... 
       
N = Total number of patients in the safety population 
n: Total number of patient’s in a given category  
Percentages are based on the total number of patient’s under safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
Programming note: 
 
This table will consist of Chemical (Protein, Glucose, Ketones and Others) and Microscopy (Pus RBC, Epithelial Cell WBC and Others) and Physical (pH, Specific Gravity, 
Colour and Others) 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 38 of 63 
 
 
 Table 14.3.12: Summary of Actual and Change from Baseline for Vital Signs by Visit 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.12 
Summary of Actual and Change from Baseline for Vital Sign by Visit 
(Safety Population) 
Lab Category 
Visit 
Statistics* 
 
Actual 
Change from baseline 
Systolic Blood Pressure (mmHg) 
Baseline 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
Visit 2 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
.... 
n 
Mean ± SD 
Q1 
Median 
Q3 
(Min, Max) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
xx 
xx.x ± xx.xx 
xx.x 
xx.x 
xx.x 
(xx.x , xx.x) 
 
........ 
 
......... 
 
......... 
 
......... 
       
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 39 of 63 
 
 
N = Total number of patients in the safety population 
Change from baseline = (Day X – baseline) 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
 
 
 
Programming note: 
 
This table will consist of Respiration Rate, Systolic Blood Pressure, Diastolic Blood Pressure, Pulse Rate and Body Temperature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 40 of 63 
 
 
Table 14.3.13: Summary of Overall interpretation for vital signs by Visit 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.13 
Summary of Overall interpretation for vital signs by Visit  
(Safety Population) 
Visit 
Categories 
Total 
 (N=xxx) 
n (%) 
Baseline  
Normal  
Abnormal-CS   
Abnormal-NCS 
 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
Visit 2 
Normal  
Abnormal-CS   
Abnormal-NCS 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
Visit 3 
 
  Normal  
Abnormal-CS   
Abnormal-NCS 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
       
N = Total number of patients in the safety population 
n: Total number of patient’s in a given category 
Percentages are based on the total number of patient’s under safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
                   
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 41 of 63 
 
 
Table 14.3.14: Summary of Overall Interpretation of Physical Examination by Visit 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Table 14.3.14 
Summary of Overall Interpretation of Physical Examination by Visit 
(Safety Population) 
Test 
 
Visit 
Categories 
Total 
 (N=xxx) 
n (%) 
General Appearance 
 
Baseline  
Normal  
Abnormal-CS   
Abnormal-NCS 
 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
Visit 2 
Normal  
Abnormal-CS   
Abnormal-NCS 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
Visit 3 
 
  Normal  
Abnormal-CS   
Abnormal-NCS 
xx (xx.x)  
xx (xx.x)  
xx (xx.x) 
… 
… 
… 
… 
… 
… 
… 
       
N = Total number of patients in the safety population 
n: Total number of patient’s in a given category  
Percentages are based on the total number of patient’s under safety population 
Analysis Dataset: XXXX 
Source Listing: Listing xx.x.x 
                   
 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 42 of 63 
 
 
 
 
 Figures 
Not Applicable 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 43 of 63 
 
 
 Patient Data Listings 
All variables out of all available case report forms (CRFs) will be listed. Each patient data listing will be paged by site and treatment, if applicable. Patient ID will be the 
first column in each listing. The Patient Data Listing which is presented below after table of contents is only an example, it will be expanded according to study objectives 
and CRF.  
 
Listing 16.2 Discontinued Patients 
 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
16.2 Discontinued Patients 
Listing 16.2.1.1  
Inclusion / Exclusion Criteria 
 
Patient ID 
Centre number 
Category 
S.No 
Question 
Status 
xxxxx 
xx 
Inclusion/Exclusion 
1 
xxxx 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 44 of 63 
 
 
 
Listing 16.2.1.2. Study Completion Details 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.1.2   
Study Completion Details 
Patient ID 
Has subject completed the 
study? 
If yes, date of study 
completion 
If no, reason for  
discontinuation 
if adverse event, or Serious 
Adverse Event please specify 
Date of death 
Other, please 
specify 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 45 of 63 
 
 
Listing 16.2.1.3. Date of Visit 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.1.3 
Date of Visit 
Patient ID 
Visit 
Date of Visit 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 46 of 63 
 
 
Listing 16.2.2. Protocol Deviations 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.2 
Protocol Deviations 
Patient ID 
Protocol Deviation identified? 
Deviation 
Description  
 
Deviation 
Category 
PD occurred in 
visit 
PD start date and time 
PD end date and 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 47 of 63 
 
 
Listing 16.2.3. Patients excluded from the analysis 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.3 
Patients excluded from the Analysis 
Patient ID 
Centre number 
Patient excluded from the analysis? 
Excluded analysis set 
Reason for Exclusion  
 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 48 of 63 
 
 
Listing 16.2.4.Demographic and baseline data 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.4 Demographic and baseline data 
Listing 16.2.4.1 
Patient Demographic and Baseline Characteristics 
Patient ID 
Center 
number 
Date of  
Informed Consent 
Date of Birth 
Age 
(years) 
Gender 
Height  
(cm) 
Weight  
(kg) 
BMI 
(kg/m2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 49 of 63 
 
 
Listing 16.2.4.2. Medical History 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.4.2 
Medical History 
Patient 
ID 
Disease / 
Condition 
System Organ Class 
Preferred Term 
Date of 
diagnoses/surgery 
(partial dates allowed) 
End Date of 
Disease/Condition/surgery 
(partial dates allowed) 
is active problem at 
start of study 
drug? 
Is subject 
receiving 
medication for 
this illness? 
 
 
 
 
 
 
 
 
 
Medical History Terms are coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 50 of 63 
 
 
Listing 16.2.4.3. Prior Medication 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.4.3 
Prior and current Medication  
Patient ID 
Medication Name 
ATC Class 
Preferred 
Term 
Dose 
Unit 
Dosage 
form 
Route 
Frequency 
Start 
Date 
Ongoing 
Stop 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
(Yes/No) 
 
Medications will be coded using  WHODDE+ HD DEC 2017 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 51 of 63 
 
 
Listing 16.2.4.4. Concomitant Medication 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.4.4 
Concomitant Medication 
Patient ID 
Medication Or 
Therapy Name 
(Generic name) 
Indication 
ATC 
Class 
Preferred 
Term 
Dose 
(Units) 
Dosage 
form 
Frequency 
Route 
Visit 
Medication 
started before 
screening? 
Start 
Date 
Stop 
Date/Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medications will be coded using  WHODDE+ HD DEC 2017 
Analysis Dataset: XXXX 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 52 of 63 
 
 
Listing 16.2.5. Compliance 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
 
Listing 16.2.5.1 Investigational Product Log 
Patient ID 
Investigational 
Product 
Visit 
Dose 
Patches 
Dispensed Date 
Total Number of 
patches dispensed 
Patches 
Returned Date 
Total Number of 
patches Returned 
Comments, 
if any 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 53 of 63 
 
 
Listing 16.2.5.2. Treatment Exposure 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.5.2 
Treatment Exposure 
Patient ID 
Treatment Start Date 
Treatment End Date 
Treatment Exposure (Days) 
 
 
 
 
 
 
 
 
 
 
 
Treatment exposure =Treatment end date – Treatment start date + 1 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 54 of 63 
 
 
Listing 16.2.6. Individual efficacy response data 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.6 Individual efficacy response data 
Listing 16.2.6.1  
Mini-Mental State Examination 
Patient ID 
Visit 
Test 
Score 
Change from baseline score 
 
 
Orientation 
Registration 
Attention-calculation 
Recall 
Language and Praxis 
Total 
 
 
 
 
 
 
 
 
 
Change from baseline = (Day X   – baseline) 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 55 of 63 
 
 
Listing 16.2.6.2. Caregiver Medication Questionnaire 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.6.2  
Caregiver Medication Questionnaire 
Patient ID 
Visit 
Date performed 
Question 
Result 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 56 of 63 
 
 
Listing 16.2.6.3. Patch Adhesion and Skin Reaction at Patch Site 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.6.3 
Patch Adhesion and Skin Reaction at Patch Site 
Patient ID 
Visit 
Question 
Result 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 57 of 63 
 
 
Listing 16.2.6.4. ADCS ADL — Severe Dementia Version 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.6.4 
ADCS ADL — Severe Dementia Version 
Patient ID 
Visit 
Question 
Result 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 58 of 63 
 
 
Listing 16.2.7. Adverse event  
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.7 Adverse event  
Listing 16.2.7.1 
Adverse Event by Patient 
Patient 
ID 
Visit 
Adverse 
Events  
TEAE 
System 
Organ 
Class 
Preferred 
Term 
Disorder 
Number 
Start 
Date 
End 
Date 
Relation 
to study 
drug 
Severity 
Action 
Taken 
Outcome 
Serious AE 
If 
SAE, 
Criteria 
/ class 
of SAE 
 
 
 
Yes/No 
 
 
 
 
 
 
 
 
 
Yes/No 
 
Adverse Events are coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 59 of 63 
 
 
Listing 16.2.7 .1.1. Serious Adverse Event by Patient 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.7.1.1 
Serious Adverse Event by Patient 
 
Patient 
ID 
Visit 
Adverse 
Events  
TEAE 
System 
Organ 
Class 
Preferred 
Term 
Disorder 
Number 
Start 
Date 
End 
Date 
Relation 
to study 
drug 
Severity 
Action 
Taken 
Outcome 
SAE, 
Criteria / 
class of 
SAE 
 
 
 
Yes/No 
 
 
 
 
 
 
 
 
 
 
Adverse Events are coded using the Medical Dictionary of Regulatory Activities (MedDRA version 20.1) 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 60 of 63 
 
 
Listing 16.2.8 Lab Parameters 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.8.1 
Lab Parameters – Urine examination 
Patient ID 
Visit 
Lab Category 
Lab Parameter 
Result 
Unit 
Interpretation 
Comment, if Abnormal 
 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 61 of 63 
 
 
Listing 16.2.8.2. Vital Signs 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.8.2 
Vital Signs 
Patient ID 
Visit 
Parameter Name 
Result 
 
 
Respiration Rate (/min) 
xxx 
 
 
SBP (mmHg) 
 
 
 
DBP (mmHg) 
 
 
 
Pulse Rate (bpm) 
 
 
 
Body Temperature (°F) 
Weight (kg) 
Clinical Significance 
 
Analysis Dataset: XXXX 
 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 62 of 63 
 
 
Listing 16.2.8.3. Physical Examination 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.8.3 
Physical Examination 
Patient ID 
Visit 
System 
Interpretation  
 Describe Abnormality 
 
 
 
 
 
 
 
 
 
 
Analysis Dataset: XXXX 
 
 
PPD


Catalogue of Tables, Listings and Figures 
Sponsor: Novartis 
Study Number: 
Version: Final 1.0   Date: 01 Dec 2022 
 
 
Page 63 of 63 
 
 
Listing 16.2.8.4. Treatment of Alzheimer Disease 
 
Novartis 
ddmmmyyyy hh:mm 
 
 Page x of y  
Listing 16.2.8.4 
Treatment of Alzheimer Disease 
Patient ID 
Visit 
Has a new AD medication added or changed from the previous visit? 
 
 
 
 
 
 
 
 
Yes/No 
Analysis Dataset: XXXX 
 
 
PPD