Conditions: Alzheimer's Disease
Keywords: SUVN-502 5-HT6 Phase 2 Cognition Donepezil Memantine Alzheimer's Disease Triple Combination Proof of Concept (POC)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 564
Healthy volunteers: no

Brief summary:
This is a phase 2a, proof-of-concept, 26-week, double-blind, multicenter, randomized, parallel group, placebo-controlled study to compare the efficacy and safety of treatment with SUVN-502 to placebo treatment in subjects with moderate Alzheimer's disease receiving stable doses of donepezil HCl and memantine HCl.

Detailed description:
This is a phase 2a, proof-of-concept, 26-week, double-blind, multicenter, randomized, parallel group, placebo-controlled study to compare the efficacy and safety of treatment with SUVN-502 to placebo treatment in subjects with moderate Alzheimer's disease receiving donepezil HCl (10 mg qd) and either memantine HCl (10 mg twice daily \[bid\]) or Namenda XR® (Extended Release, 28 mg qd) or the combination therapy, Namzaric™

The primary objective of the study is to evaluate the efficacy of a serotonin receptor subtype 6 (5-HT6) antagonist, SUVN-502, compared to placebo, as adjunct treatment in subjects with moderate Alzheimer's disease (Mini-Mental State Examination \[MMSE\] score of 12 to 20) currently treated with the acetylcholinesterase inhibitor, donepezil hydrochloride (HCl), and the N-methyl-D-aspartic acid (NMDA) antagonist, memantine HCl. Efficacy will be assessed by the 11-item Alzheimer's Disease Assessment Scale for Cognitive Behavior (ADAScog-11) after 26 weeks of treatment.

Arms:
arm 1: SUVN-502 Low dose adjunct to base treatment with Donepezil and Memantine arm 2: SUVN-502 High dose adjunct to base treatment with Donepezil and Memantine arm 3: Placebo adjunct to base treatment with Donepezil and Memantine

Interventions: intervention 1: SUVN-502 intervention 2: Placebo intervention 3: Donepezil intervention 4: Memantine
Intervention descriptions: intervention 1: Once-daily, tablets, orally intervention 2: Once-daily, tablets, orally intervention 3: Donepezil HCl (10 mg, once a day) intervention 4: Memantine HCl (10 mg, twice a day or 28 mg extended-release, once a day).

Protocol document:
Prot_000.pdf: 
 
 
Clinical Study Protocol 
Title: A Phase 2A Multicenter, Randomized, Double-Blind, Parallel Group, 26-Week, Placebo-Controlled 
Study of 50 mg and 100 mg of SUVN-502 in Subjects with Moderate Alzheimer’s Disease Currently 
Treated with Donepezil Hydrochloride and Memantine Hydrochloride 
Protocol Number: CTP2S1502HT6 
NCT02580305 
Date: 02 March 2016 












S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 of 1 4 3  
0 2 Mar c h 2 0 1 6  
Tr e at me nt  
E li gi bl e s u bj e cts will r e c ei ve d o u bl e -bli n d or al a d mi nistr ati o n of o ne of t hr e e 
tr e at me nts: S U V N-5 0 2 ( 5 0 m g  q d ), S U V N-5 0 2 ( 1 0 0  m g  q d ), or pl ac e b o ( q d) 
i n a 1: 1: 1  r ati o. 
Thr o u g h o ut t he st u d y, all s u bj e cts will als o c o nti n ue t o r e c ei ve d o ne pe zil H Cl 
( 1 0 m g q d) a n d me ma nti ne H Cl ( 1 0 m g bi d) or Na me n da X R ®  
( 2 8 m g  me ma nti ne H Cl e xt e n de d -r el e ase q d)  or t he c o m bi nati o n t her a p y, 
Na mzari c ™ ( 2 8  m g  me ma nti ne H Cl e xt e n de d -r el e as e / 10 m g d o ne pe zil H Cl ) 
q d . 
S u bj e cts will be tr e at e d wit h S U V N -5 0 2 or pl ac e b o f or a t ot al of 2 6  we e ks 
f oll o we d b y a 4-we e k si n gl e-bli n d  pl ac e b o was h o ut peri o d . D uri n g t he 
was h o ut peri o d, all s u bj e cts will r e c ei ve pl ac e b o i n a d diti o n t o d o ne pe zil H Cl 
a n d me ma nti ne H Cl.  
S U V N -5 0 2 will be s u p pli e d as i de nti c all y a p pe ari n g t a bl ets t hat c o nt ai n 
eit her 5 0  m g or 1 0 0  m g o f S U V N -5 0 2 . Pl ac e b o t a bl ets mat c hi n g S U V N -5 0 2 
t a bl ets will als o be s u p pli e d. 
Ge neri c f or m ul ati o ns of d o ne pe zil H Cl ( 1 0 m g) a n d me ma nti ne H Cl ( 1 0 m g) 
will be pr o vi de d b y t he S p o ns or a n d dis pe ns e d t o t he s u bj e cts fr o m bas eli ne . 
S u bj e cts tr e at e d wit h Na me n da X R ®  or Na mzari c ™ s h o ul d c o nti n ue t o t a ke 
t heir o wn me di c ati o n as pr es cri be d b y t heir pr es cri bi n g  p h ysi ci a n.  
N u m be r of S u bje ct s 
A t ot al of 5 3 7  s u bj e cts will be e nr oll e d a n d r a n d o mi ze d i nt o o ne of t hr e e 
tr e at me nt gr o u ps: S U V N -5 0 2 5 0 m g, S U V N -5 0 2 1 0 0 m g,  or pl ac e b o 
(1 7 9  s u bj e cts per gr o u p ). 
P o p ul ati o n  
The st u d y p o p ul ati o n will i ncl u de mal e or f e mal e s u bj e cts, 5 0 t o 8 5 ye ars of 
a ge, wit h  m o der at e de me nti a d ue t o pr o ba bl e Al z hei mer’s dis e as e bas e d o n 
t he Nati o nal I nstit ut e of Ne ur ol o gi c al a n d C o m m u ni c ati ve Dis e as es a n d 
Str o ke/ Al z hei mer's Dis e as e a n d Rel at e d Dis or ders Ass o ci ati o n 
(NI N C D S -A D R D A ) crit eri a, di a g n os e d at l e ast 1 ye ar pri or t o t he st u d y an d 
r e c ei vi n g st a bl e d os es f or at l e ast 3 m o nt hs of d o ne pe zil H Cl ( 1 0 m g q d ) a n d 
eit her me ma nti ne H Cl ( 1 0 m g bi d ) or Na me n da X R ®  ( 2 8 m g me ma nti ne H Cl 
e xt e n de d-r el e as e q d)  or t he c o m bi nati o n t her a p y, Na mzari c ™ 
( 2 8 m g  me ma nti ne H Cl e xt e n de d -r el e ase / 1 0 m g d o ne pe zil H Cl ) q d. 
Cri t e ri a f o r E v al u ati o n 
of Effi c ac y  
The pri mar y effi c ac y vari a bl e  will be t he A D A S -C o g . 
Se c o n dar y effi c ac y vari a bl es  will i ncl u de t he f oll o wi n g: 
•  
C D R -S B  
•  
M M S E  
•  
A D C S - AD L  
•  
N PI  
•  
C- S D D  
Cri t e ri a f o r E v al u ati o n 
of S afet y  
Saf et y e val uati o ns will i ncl u de t he r e p orti n g of A Es  t hr o u g h o ut t he st u d y a n d 
bl o o d pr ess ur e me as ur e me nt, E C G, p h ysi c al  a n d ne ur ol o gi c al e xa mi nat i o n, 
a n d ass ess me nts of s ui ci dalit y usi n g t he C- S S R S  at e ac h visit . Bl o o d a n d 
uri ne s a m pl es f or l a bor at or y  e val uati o ns will be c oll e ct e d at s cr e e ni n g, 
bas eli ne a n d We e ks 4 ( li ver f u ncti o n t ests o nl y) 1 3, 2 6 a n d 3 0.   
A n  i n de pe n de nt Dat a a n d Saf et y M o nit ori n g B o ar d ( D S M B) will be 
ass e m bl e d t o peri o di c all y r e vi e w a n d e val uat e ac c u m ul at e d st u d y dat a f or 
s u bj e ct s af et y, st u d y c o n d uct a n d pr o gr ess a n d, if a p pr o pri at e, effi c ac y. The 
D S M B will  be r es p o nsi bl e f or ma ki n g r e c o m me n dati o ns c o nc er ni n g 
c o nti n uati o n, m o difi c ati o n, or t er mi nati o n of t he st u d y, bas e d o n t heir 
i n de pe n de nt e val uati o n of st u d y r el at e d s af et y dat a. The D S M B r ol e a n d 
acti viti es ar e des cri be d i n det ail i n t he D S M B c hart er . The D S M B will c o nsist 
of a c hair pers o n a n d at l e ast 2  a d diti o nal me m bers  i ncl u di n g 1 st atisti cia n. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 of 1 4 3  
0 2 Mar c h 2 0 1 6  
Ot he r Crit e ri a  
At bas eli ne, a bl o o d s a m pl e will be dr a wn  f or A P O -E  ge n ot y pe t esti n g.  
Pl as ma s a m pl es will be a nal yze d f or l e vels of S U V N -5 0 2 a n d its pri mar y 
met a b olit e  (M 1 of S U V N -5 0 2) , at st e a d y st at e ( We e k 4 of tr e at me nt) a n d at 
t he e n d of st u d y ( We e k 2 6) t o gat her i nf or mati o n o n p o p ul ati o n 
p har mac o ki neti cs.  
Pl as ma s a m pl es will be a nal yze d f or l e vels of d o ne pe zil a n d me ma nti ne at 
s cr e e ni n g, at We e k 4 of tr e at me nt a n d at t he e n d of st u d y ( We e k 2 6) t o 
det er mi ne c o m pli a nc e wit h st u d y me di c ati o n.  
St ati sti c al Met h o ds  
A t ot al of 5 3 7  s u bj e cts will be r a n d o mi ze d i nt o o ne of t hr e e tr e at me nt gr o u p s, 
S U V N -5 0 2 ( 5 0 m g ), S U V N-5 0 2 ( 1 0 0 m g) or pl ac e b o ( 1 7 9  s u bj e cts per 
gr o u p ). Wit h a s a m pl e si ze of 5 3 7  s u bj e cts, t her e is at l e ast 8 0 % p o wer t o 
det e ct a 2 -p oi nt dr u g -pl ac e b o diff er e nc e o n t he A D AS- C o g  wit h a st a n dar d 
de vi ati o n o f 6 , a t wo-si de d 5 % si g nifi c a nc e l e vel a n d a dr o p-o ut r at e of 
≤2 0 %.  
Effi c ac y a nal ys es will be perf or me d o n t he m o difi e d I nt e nt t o Tr e at (I T T) 
p o p ul ati o n a n d  t he E val ua bl e  P o p ul ati o n ( E P) . The m o difi e d I T T  p o p ul ati o n 
is defi ne d as all r a n d o mi ze d s u bj e cts who r e c ei ve at l e ast o ne d os e of st u d y 
me di c ati o n a n d ha ve  o ne p ost -bas eli ne e val uati o n of t he pri mar y effi c ac y 
vari a bl e . The E P is defi ne d as all r a n d o mi ze d s u bj e cts wh o c o m pl et e 
2 6  we e ks of tr e at me nt, ar e c o m pli a nt wit h t a ki n g st u d y me di c ati o n ( ≥8 0 %), 
a n d ha ve  n o si g nifi c a nt pr ot o c ol de vi ati o n . 
Saf et y a nal ys es will be perf or me d o n t he Saf et y P o p ul ati o n ( S P), defi ne d as 
all r a n d o mi ze d s u bj e cts wh o r e c ei ve at l e ast o ne d os e of st u d y me di c ati o n.  
P har mac o ki neti c ( P K) a nal ys es will be perf or me d o n t he S P . 
St atisti c al a nal ysis of t he pri mar y e n d p oi nt will be perf or me d usi n g mi xe d 
m o del r e pe at e d me as ur es ( M M R M) wit h o ut i m p ut ati o n of missi n g dat a . The 
M M R M m o del will i ncl u de fi xe d c at e g ori c al eff ects f or tr eat me nt, p o ol e d 
sit e, we e k, a n d tr e at me nt-b y -we e k i nt e r acti o n, as well as a c o nti n u o us 
c o vari at e of bas eli ne s c or e a n d bas eli ne s c or e-b y -we e k i nt er acti o n . An 
u nstr uct ur e d c o vari a nc e matri x will be us e d t o m o del t he vari ati o n of t he 
r e pe at e d me as ur es wit hi n pati e nt. 
The pri mar y effi c ac y a nal ysis will c o m par e t he eff e ct of e ac h d os e of 
S U V N -5 0 2 ( 5 0 m g a n d 1 0 0 m g), s e par at el y, t o t he eff e ct of pl ac e b o, f or t he 
c ha n ge fr o m bas el i ne t o we e k 2 6 of t he A D A S-C o g  s c or e usi n g t he m o difi e d 
I T T  p o p ul ati o n a n d  t he a b o ve me nti o ne d M M R M m o del. N o a dj ust me nt f or 
m ulti pli cit y will be ma de .  
Se c o n dar y effi c ac y a nal ys es i ncl u de t he c o m paris o n of t he eff e ct of 
S U V N -5 0 2 ( 5 0  m g a n d 1 0 0 m g) t o t he eff e ct of pl ac e b o usi n g t he s a me 
M M R M a p pr o ac h as des cri be d a b o ve f or t he f oll o wi n g me as ur es: 
•  
A D A S -C o g  at We e ks 4 a n d 1 3  
•  
C D R -S B at W e e ks 4 , 1 3 a n d 2 6 
•  
M M S E at W e e ks 4, 1 3 a n d 2 6  
•  
A D C S -A D L  at  W e e ks 4, 1 3 a n d 2 6  
•  
N PI at W e e ks 4, 1 3 a n d 2 6  
•  
C- S D D at We e ks, 4, 1 3 a n d 2 6  
Se nsiti vit y a nal ys es f or t he pri mar y a n d s e c o n dar y vari a bl es usi n g l ast 
o bs er vati o n c arri e d f or war d ( L O C F) a n d usi n g t he E P a nal ysis s et will be 
c o n d uct e d. 
E x pl or at or y a nal ys es of t he pri mar y a n d s e c o n dar y effi c ac y crit eria will be 
c o n d uct e d bas e d o n A P O-E 4 c arri er st at us.  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
8 of 1 4 3  
0 2 Mar c h 2 0 1 6  
Sc he d ule   of Pr oce d ure s  
St u d y  pe ri o d  
Sc re e ni n g  
B as e li ne  
Tre at me nt Pe ri o d  
E n d of  Tre at me nt  
F oll o w -u p  
Ti me  
 
D a ys  -2 8 t o -1 4 a 
 
D a y  1 a 
We e k 4  
D a y  2 8 ± 2  
We e k 1 3  
D a y  9 1 ± 2  
We e k 2 6  
D a y 1 8 2 ± 3  
o r e arl y wit h dr a wal  
We e k 3 0  
D a y 2 1 0 ± 2  
Vis it n u m be r  
1  
2  
3  
4  
5  
6  
Pr o c e d ure s  
 
 
 
 
 
 
I nf or me d  Co ns e nt  
X  
 
 
 
 
 
I nclusio n  / E xclusio n  Criteria 
X  
X  
 
 
 
 
D e m o gra p hics,  Me dic al  Hist or y  
X  
X  
 
 
 
 
Prior  a n d C o nc o mita nt  Me dic atio ns  
X  
X  
X  
X  
X  
X  
M RI or C T Sc a n (if N e c ess ar y)  
X  
 
 
 
 
 
Blo o d  Sa m ple  f or A P O -E Ge n ot y pe  T e stin g 
 
X  
 
 
 
 
St u d y  Tre at me nt D is pe ns atio n b  
 
X 
X 
X 
X 
 
M M S E a n d A D A S -C o g  
X  
X  
X  
X  
X  
 
M o difie d  H a c hins ki  Is c he mic  Sc ale  
X  
 
 
 
 
 
C D R -S B, A D C S -A D L, a n d N PI  
 
X  
X  
X  
X  
 
C -S D D  
X  
X  
X  
X  
X  
X  
C -S S R S  
X  
X  
X  
X  
X  
X  
Re vie w  of A Es  
X  
X  
X  
X  
X  
X  
La b orat or y  Tests  
X c 
X 
X d  
X 
X c 
X 
Blo o d  Press ure Me as ure me nts  
X  
X  
X  
X  
X  
X  
E C G  
X 
X 
X e 
X  e 
X e 
X 
P h ysic al  a n d N e ur olo gic al  E xa minatio n  
X  
X  
X  
X  
X  
X  
Plas ma L e vels of S U V N -5 0 2  a n d M 1  of S U V N -5 0 2  
 
 
X  f 
 
X  f 
 
Plas ma Le vels  of D o ne pe zil  a n d  M e ma ntine  
X 
 
X  f 
 
X  f 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
9 of 1 4 3  
0 2 Mar c h 2 0 1 6  
Sc he d ule   of Pr oce d ure s  ( C o nti n ue d)  
A D A S -C o g = Alz h ei mer’s Dis e ase Ass ess me nt S c al e; A D C S -A D L = Alz hei mer’s Dis e as e C o o per ati ve St u dy Acti vit y of D ail y Li vi n g; A E = a d v erse e ve nt; 
A P O -E = A p oli p o pr ot ei n E; C D R -S B = Cli ni c al De me nti a R ati n g S c al e – S u m of B o x es; C -S D D = C or nell S c al e of De pressi o n a n d De me nti a; C -S S R S = C ol u m bi a 
S ui ci d e S e verity R ati n g S c ale; C T = C o m p ut e d T o m o gr a p hy; E C G = El e ctr oc ar d i o gr a m; M HI S = M o difi e d H a c hi ns ki Is c h e mi c S c al e; M M S E = Mi ni -Me nt al St ate 
Ev al u ati o n; M RI = M a g n etic Res o n a nce I m a gi n g; N PI = Ne ur o ps yc hi atri c I n v e nt or y.  
 
N ot e:  It is str o n gl y r e c o m me n de d t h at o n e r at er is assi g n e d f or e a c h s u bj ect f or e a c h of t h e f oll o wi n g assess me nt s c al es s o t h at o n e r ater s c or es a s u bje ct’s 
ass ess me nt f or t h e e ntir e st u dy: M M S E, A D A S -C o g , C D R-S B, A D C S -A D L, N PI, C -S D D, a n d C -S S R S.  
 
a.  F or S cr e e ni n g a n d B as eli ne Visits, t h e f oll o wi n g ass ess me nts, i n cl u de d i n st u dy e ntry crit eri a, s h o ul d b e p erf o r me d first i n or d er t o li mit t h e n u m ber of 
ass ess me nts p erf or me d f or s u bj ects w h o d o n ot me et t he st u dy e ntry crit eri a: M M S E, t h e M HI S, C -S D D, C -S S R S, E C G, pr e g n a n cy t est (f or w o me n of 
c hil d b e ari n g p ot e nti al), a n d l a b or at or y t ests.  
b.  O n t h e d a y of t h e st u d y  visits, s u bj ects will b e i nstr u ct e d n ot t o t a ke t h eir tr e at me nt at h o me, as tr e at me nt will b e dis pe nse d at t h e st u dy ce nt er . 
c.  A uri n e pr e g n a ncy t est will b e d o n e at s cr e e ni n g a n d We e k 2 6 visit f or w o me n of c hil d be ari n g p ot e nti al. A p ositi ve uri ne t est  will  b e c o nfir me d b y a 
s er u m pr e g n a ncy t est. 
d.  At We e k 4, l a b or at or y t ests will o nl y i n cl u d e li v er f u ncti o n t ests.  
e. 3 h o urs aft er st u dy tr e at me nt a d mi nistr ati o n, i.e. t h e a p pr oxi m at e ti me of m a xi m u m c o n ce ntr ati o n of S U V N -5 0 2.  
f. 
Pl as m a s a m pl es f or P K ass ess me nts wil l b e c oll ect e d b ef ore st u d y dr u gs ar e a d mi nist er e d t o t h e s u bje cts.  




S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T A B L E  O F C O N T E N T S  
P R O T O C O L S Y N O P SI S  .................................................................................................. 5 
LI S T O F S T U D Y P E R S O N N E L  .................................................................................... 1 0 
LI S T  O F A B B R E VI A TI O N S A N D  D E FI NI TI O N S O F T E R M S ............................... 1 5 
1  
I N T R O D U C TI O N................................................................................................ 1 7  
1. 1  
B ac k gr o u n d ...................................................................................................... 1 7  
1. 1. 1  
Al z hei mer’s Dis eas e  ............................................................................ 1 7 
1. 1. 2  
S u m mar y of Fi ndi n gs fr o m N o n- Cli ni cal St udi es  ............................... 1 7 
1. 1. 2. 1  
P h ar m ac ol o gy ................................................................................ 1 7  
1. 1. 2. 2  
P h ar m ac oki neti cs a n d M et a b olis m ................................................ 1 8  
1. 1. 2. 3  
T oxi c ol o gy ...................................................................................... 1 8  
1. 1. 3  
S u m mar y of Fi ndi n gs fr o m Pr e vi o us Cli ni cal St udi es......................... 1 9  
1. 2  
R ati o nale  .......................................................................................................... 1 9 
1. 3  
Ris k -Be nefit Assess me nt  ................................................................................. 2 0 
2  
S T U D Y O B J E C TI V E S  ........................................................................................ 2 2 
2. 1  
Pri  ma r y O bj e cti ve  ........................................................................................... 2 2 
2. 2  
Se c o n da r y O bj e cti ve (s)  ................................................................................... 2 2 
3  
O V E R A L L D E SI G N A N D P L A N O F T H E S T U D Y  ....................................... 2 3 
3. 1  
O ve r vie w  .......................................................................................................... 2 3 
3. 2  
Crit e ri a f or E v al uati o n of t he St u dy.............................................................. 2 4  
3. 2. 1  
Pri mar y Effi cac y Criteri o n  ................................................................... 2 4 
3. 2. 2  
Sec o ndar y Effi cac y Criteri a  ................................................................. 2 5 
3. 2. 3  
Safet y Criteri a  ...................................................................................... 2 5 
3. 2. 4  
Ot her Criteri a  ....................................................................................... 2 5 
3. 3  
J ustific ati o n of t he St u dy Desi g n  ................................................................... 2 5 
4  
S T U D Y P O P U L A TI O N  ...................................................................................... 2 6 
4. 1  
I ncl us i o n C rit e ri a ............................................................................................ 2 6 
4. 2  
E xcl usi o n C rit e ri a  ........................................................................................... 2 7 
4. 3  
S u bj e ct Wit h dr a w al a n d Re pl ace me nt .......................................................... 2 8 
4. 4  
Pl a n ne d S a  m ple  Siz e  a n d N u m be r of St u dy Ce nt e rs  ................................... 2 9 
4. 5  
S u bj e ct I de nt ific ati o n a n d  R a n do  miz ati o n  ................................................... 2 9 
4. 5. 1  
S ubj ect I de ntifi cati o n  ........................................................................... 2 9 
4. 5. 2  
Ra nd o mi za ti o n Sc he  me ........................................................................ 3 0  
4. 5. 3  
All ocati o n/ Ra nd o mi zati o n of S ubj ects t o Tr eat me nt  ........................... 3 0 
5  
S T U D Y D R U G  ..................................................................................................... 3 1 
5. 1  
I de ntit y ............................................................................................................. 3 1 
5. 1. 1  
I nvesti gati o nal Tr eat me nt: S U V N- 5 0 2 a nd Matc hi n g Pl ace b o  ........... 3 1 
5. 1. 2  
Ot her St ud y Dr u gs  ............................................................................... 3 1 
5. 2  
A d mi nist r ati o n ................................................................................................. 3 1  
5. 2. 1  
I nvesti gati o nal Tr eat me nt: S U V N- 5 0 2 a nd Matc hi n g Pl ace b o ........... 3 1 
5. 2. 2  
Ot her St ud y Dr u gs  ............................................................................... 3 2 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
5. 3  
P ac k a gi ng, L a beli ng a n d St or a ge .................................................................. 3 2  
5. 3. 1  
I nvesti gati o nal Tr eat me nt: S U V N- 5 0 2 a nd Matc hi n g Pl ace b o ........... 3 2 
5. 3. 2  
Ot her St ud y Dr u gs  ............................................................................... 3 2 
5. 4  
Bli n di ng a n d B re a ki ng t he Bli n d  ................................................................... 3 2 
5. 5  
Dr ug  Acc o u nt a bilit y  ........................................................................................ 3 3 
5. 6  
C o m pli a nce  ...................................................................................................... 3 3 
5. 7  
Pre vi o us a n d C o nc o  mit a nt  Me dic ati o ns  ....................................................... 3 4 
5. 7. 1  
Per mit te d C o nc o mita nt Me di cati o ns.................................................... 3 4 
5. 7. 2  
Pr o hi bite d C o nc o mita nt Me di cati o ns................................................... 3 5  
6  
V A RI A B L E S A N D M E T H O D S O F A S S E S S M E N T  ....................................... 3 6 
6. 1  
Effic ac y V ari a bles  ........................................................................................... 3 6 
6. 1. 1  
Pri mar y Effi cac y Vari a bl e  ................................................................... 3 6 
6. 1. 2  
Sec o ndar y Effi cac y Vari a bl es  .............................................................. 3 6 
6. 1. 2. 1  
Cli ni c al De me nti a R ati n g Sc al e – S u m of B oxes ........................... 3 6  
6. 1. 2. 2  
Mi ni- M e nt al St at e Ex a mi n ati o n ..................................................... 3 6  
6. 1. 2. 3  
Alz hei mer’s Dis e as e C o -o per ati ve St u dy Acti vit y of D ail y 
Li vi n g ( A D C S- A D L)  ....................................................................... 3 7 
6. 1. 2. 4  
Ne ur o ps yc hi atri c I nve nt ory ............................................................ 3 7 
6. 1. 2. 5  
C or nell Sc ale f or De pr essi o n a n d De me nti a ................................. 3 7  
6. 2  
S af et y V ari a bles ............................................................................................... 3 8  
6. 2. 1  
A d vers e E ve nts .................................................................................... 3 8  
6. 2. 1. 1  
C oll ecti o n of Advers e Eve nts  ......................................................... 3 8 
6. 2. 1. 2  
Defi niti o ns  ...................................................................................... 3 8 
6. 2. 1. 3  
Ass ess me nt of Advers e Eve nts  ........................................................ 3 8 
6. 2. 1. 4  
Rec or di n g Advers e Eve nts  ............................................................. 4 0 
6. 2. 1. 5  
Re p orti n g Seri o us Advers e Eve nts  ................................................. 4 0 
6. 2. 1. 6  
F oll o w- u p of Advers e Eve nts ......................................................... 4 1  
6. 2. 1. 7  
Pr e g n a ncy ...................................................................................... 4 1  
6. 2. 2  
La b or at or y Vari a bl es ............................................................................ 4 2  
6. 2. 3  
Vital Si g ns  ............................................................................................ 4 4 
6. 2. 4  
El ectr ocar di o gr a ms  .............................................................................. 4 4 
6. 2. 5  
P h ysi cal a nd Ne ur ol o gi cal E xa  mi na ti o ns  ............................................ 4 4 
6. 2. 6  
A d diti o nal Safet y Ass ess me nts ............................................................ 4 5  
6. 2. 6. 1  
C ol u m bi a S ui ci de Severit y R ati n g Sc al e ........................................ 4 5  
6. 3  
De mo g r a p hics a n d B as eli ne C ha r act e ristics ................................................. 4 6 
6. 3. 1  
S ubj ect De m o gr a p h y ............................................................................ 4 6  
6. 3. 2  
Dis eas e Hist or y  .................................................................................... 4 6 
6. 3. 3  
Me di cal Hist or y .................................................................................... 4 6  
6. 3. 4  
Pr e vi o us a nd C o nc o  mi ta nt Me di cati o ns  .............................................. 4 6 
6. 4  
Ot he r Ass ess me nts  .......................................................................................... 4 6 
6. 4. 1  
Scr ee ni n g Ass ess me nts  ........................................................................ 4 6 
6. 4. 1. 1  
M RI a n d C T s c a n ........................................................................... 4 6  
6. 4. 1. 2  
M o difi e d H ac hi ns ki Is c he mi c Sc al e ( M HI S) .................................. 4 6  
6. 4. 1. 3  
N ati o n al I nstit ut e of Ne ur ol o gi c al a n d C o m m u ni c ati ve 
Dis e as es a n d Str oke/ Alz hei mer's Dis e as e a n d Rel at e d 


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Ve rsi o n 2  
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0 2 Mar c h 2 0 1 6  
Dis or ders Ass oci ati o n Crit eri a f or Pr o b a bl e Alz hei mer’s 
Dis e as e  ........................................................................................... 4 7 
6. 4. 2  
A p oli p o pr otei n E Ge not ype Testi n g .................................................... 4 7  
6. 4. 3  
P har mac o ki ne ti cs  ................................................................................. 4 7 
7  
S T U D Y C O N D U C T  ............................................................................................. 4 8 
7. 1  
Sc he d ule of Pr oce d ures  ................................................................................... 4 8 
7. 2  
Pr oce d ures by Visit  ......................................................................................... 5 1 
7. 2. 1  
Scr ee ni n g ( Visit 1, Da y - 2 8 t o - 1 4) ...................................................... 5 1  
7. 2. 2  
Bas eli ne Visit ( Visit  2, Da y 1) ............................................................. 5 1 
7. 2. 3  
Wee k 4 Visit ( Visit 3, Da y 2 8) ............................................................ 5 2  
7. 2. 4  
Wee k 1 3 Visit ( Visit 4, Da y 9 1) .......................................................... 5 2  
7. 2. 5  
Wee k 2 6 Visit ( Visit 5, Da y 1 8 2) ........................................................ 5 3  
7. 2. 6  
Wee k 3 0 Visit ( Visit 6, Da y 2 1 0) ........................................................ 5 3  
7. 2. 7  
Earl y Ter mi nati o n a nd F oll o w -Up  Visits ............................................. 5 3 
8  
S T A TI S TI C A L M E T H O D S  ............................................................................... 5 4 
8. 1  
St u dy S u bj e cts  ................................................................................................. 5 4 
8. 1. 1  
Dis p ositi o n of S ubj ects ........................................................................ 5 4  
8. 1. 2  
Pr ot oc ol De vi ati o ns .............................................................................. 5 4  
8. 1. 3  
A nal ysis Sets  ........................................................................................ 5 4 
8. 2  
Ge ne r al C o ns i de r ati o ns  .................................................................................. 5 5 
8. 3  
De mo gr a p hics,  Me dic al Hist or y, B as eli ne C har act e ristics, a n d 
C o nc o  mit a nt  Me dic at i o ns  ............................................................................... 5 6 
8. 4  
Tre at me nt C o  m pli a nce  ................................................................................... 5 6 
8. 5  
Effic ac y A nal ys es ............................................................................................. 5 6  
8. 5. 1  
Pri mar y Effi cac y A nal ysis  ................................................................... 5 6 
8. 5. 1. 1  
Hy p ot hes es t o be Test e d ................................................................. 5 6  
8. 5. 1. 2  
St atistic al Met h o ds ......................................................................... 5 6  
8. 5. 1. 3  
S u b gr o u p An al ys es ......................................................................... 5 7  
8. 5. 2  
Sec o ndar y Effi cac y A nal ys es ............................................................... 5 7  
8. 6  
S af et y A nal ys es ................................................................................................ 5 7  
8. 6. 1  
A d vers e E ve nts .................................................................................... 5 7  
8. 6. 2  
La b or at or y Ass ess me nts ...................................................................... 5 7  
8. 6. 3  
Vital Si g ns  ............................................................................................ 5 8 
8. 6. 4  
El ectr ocar di o gr a ms  .............................................................................. 5 8 
8. 6. 5  
P h ysi cal a nd Ne ur ol o gi cal E xa  mi na ti o ns  ............................................ 5 8 
8. 6. 6  
A d diti o nal Safet y Ass ess me nts ............................................................ 5 8  
8. 7  
P ha r m ac o ki netics A nal ys es ............................................................................ 5 8  
8. 8  
I nt e ri m A na l ys e s.............................................................................................. 5 8  
8. 9  
De te r mi nati o n of  S a m ple Siz e  ........................................................................ 5 8 
9  
E T HI C A L, L E G A L, A N D A D MI NI S T R A TI V E A S P E C T S ........................... 5 9 
9. 1  
D at a Q ualit y Ass ur a nce .................................................................................. 5 9  
9. 1. 1  
Data bas e Ma na ge me nt a nd Q ualit y C o ntr ol  ........................................ 5 9 
9. 2  
C as e Re port Fo r ms a n d S o urce D oc u me nt ati o n  .......................................... 5 9 
9. 2. 1  
Data C oll ecti o n  .................................................................................... 6 0 


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Ve rsi o n 2  
1 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
9. 3  
Access t o S o urce D at a ..................................................................................... 6 0  
9. 4  
D at a Pr ocessi ng ............................................................................................... 6 1  
9. 5  
Arc hi vi n g St u d y Re c or ds  ................................................................................ 6 1 
9. 6  
G o o d Cli nic al Pr actice  .................................................................................... 6 1 
9. 7  
I nf or me d  C o ns e nt............................................................................................ 6 1  
9. 8  
Pr ot oc ol A p pr o v al a n d A me n d me nt .............................................................. 6 2 
9. 9  
D at a a n d S af et y M o nit o ri ng B o a r d ............................................................... 6 2  
9. 1 0  
D ur at i o n of t he  St u dy ...................................................................................... 6 2  
9. 1 1  
Pre mat ure Te r mi n ati o n of t he St u dy  ............................................................ 6 2 
9. 1 2  
C o nfi de nti a lit y  ................................................................................................. 6 3 
9. 1 3  
Ot he r Et hic al a n d  Re g ul at o r y  Iss ue s ............................................................. 6 3 
1 0  
R E F E R E N C E LI S T  ............................................................................................. 6 4 
1 1  
A P P E N DI C E S  ...................................................................................................... 6 5 
 
T a ble s  i n  Te xt  
Ta bl e 1: C o mp ositi o n of S U V N- 5 0 2 a nd Pl ace b o Ta bl ets ................................................ 3 1  
Ta bl e  2: La b or at or y Ass ess me nts ...................................................................................... 4 3 
Ta bl e  3: Sc he d ul e of Pr oce d ur es ........................................................................................ 4 9  
 
Fi g ure s  i n  Te xt  
Fi g ur e 1: St ud y Desi g n  ...................................................................................................... 2 3 
 
List of A p pe n dice s  
A p pe ndi x 1: Al z hei mer’s Dis eas e Ass ess me nt  Scal e - C o gniti ve Be ha vi or (A D A S -
C o g)    ........................................................................................................................... 6 5 
A p pe ndi x 2: Cli ni cal De me nti a Rati n g Scal e  .................................................................... 7 7 
A p pe ndi x 3: Mi ni- Me ntal State E xa mi nati o n  .................................................................... 8 5 
A p pe ndi x 4: Al z hei mer’s Dis eas e C o -O per ati ve St ud y Acti vit y Of Dail y L i vi n g............ 8 6 
A p pe ndi x 5: Ne ur o ps yc hi atri c I nve nt or y 1 2- Ite m ............................................................. 9 4 
A p pe ndi x 6: C or nell Scal e F or De pr essi o n A nd De me nti a ............................................. 1 0 8  
A p pe ndi x 7: Ge ner al Ne ur ol o gi cal E xa  m  ........................................................................ 1 1 0 
A p pe ndi x 8: C ol u m bi a S ui ci de Se verit y Rati n g Scal e .................................................... 1 1 3  
A p pe ndi x 9: M o difi e d Hac hi ns ki Is c he mi c Scal e............................................................ 1 1 9  
A p pe ndi x 1 0: Nati o nal I nstit ute  of Ne ur ol o gi cal a nd C o m muni cati ve  Dis eas es A nd 
Str o ke/ Al z hei mer's  Dis eas e a nd Rel ate d Dis or ders Ass oci ati o n Criteri a f or 
Pr o ba bl e Al z hei mer’s Dis eas e ................................................................................... 1 2 0  
A p pe ndi x 1 1: S u m mar y of C ha n ges f or Pr ot oc ol A me nd me nt 1 ( Versi o n 2) ................. 1 2 2  
 


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C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
LI S T  O F A B B R E VI A TI O N S  A N D D E FI NI TI O N S  O F  T E R M S  
5- H T 6 
Ser ot o ni n r ece pt or s ubt ype 6  
A D A S -C o g  
Al z hei mer’s Dis eas e Ass ess me nt Scal e  f or C o gniti ve Be ha vi or 
A D C S -A D L  
Al z hei mer’s Dis eas e C o o per ati ve St ud y Acti vit y of Dail y Li vi ng  
A E  
A d vers e e ve nt 
A L T  
Al a ni ne a mi notr a nsfer as e  
A P O - E 
A p oli p o pr otei n E 
A S T  
As partate a mi notr a nsfer as e  
A T C  
A nat o mi cal T her a pe uti c C he mi cal [ Cl assifi cati o n S yste m]  
BI D, bi d  
T wi ce dail y  
c A M P 
C ycli c a de nosi ne mo no p hos p hate 
C D R  
Cli ni cal De me nti a  Rati ng Scal e  
C D R -S B  
Cli ni cal De me nti a  Rati ng Scal e – S u m  of B o xes  
C R E -Luc  
C ycli c a de nosi ne mo no p hos p hate  ( c A M P) r es p o ns e el e me nt -
l ucifer as e 
C- S D D  
C or nell Scal e of De pr essi o n a nd De me nti a  
C- S S R S  
C ol u mbi a S ui ci de Se verit y Rati ng  Scal e  
C T  
C o mp ute d  t o mo gr a p hy  
C Y P 3 A 4  
C yt oc hr o me  P 4 5 0 3 A 4 
D S M B  
Data Safet y M o nit ori ng  B oar d  
E C G  
El ectr ocar di o gr a m  
e C R F 
El ectr o ni c cas e r e p ort f or m  
E D C  
El ectr o ni c data ca pt ur e  
E M A  
E ur o pea n Me di ci nes A ge nc y  
F D A  
F o o d a nd Dr ug A d mi nistr ati o n 
G G T  
Ga m ma -gl uta  m yl  tr a ns pe pti das e  
H b A 1c  
He mo gl o bi n  A 1c or gl ycate d he mo gl o bi n 
H Cl  
H ydr oc hl ori de 
I C F 
I nf or me d  c o ns e nt f or m 
I C H 
I nter nati o nal  C o nfer e nce o n Har mo ni zati o n 
I E C 
I nde pe nde nt  Et hi cs C o m mittee 
I R 
I m me di ate  r el eas e  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
I R B 
I nstit uti o nal  Re vi e w B oar d 
I T T 
I nte nt-t o-tr eat; i nte nti o n-t o-tr eat 
I V R S 
I nter acti ve Voi ce Res p o ns e S yste m 
K b  
Diss oci ati o n c o nsta nt  
Ki  
I nhi biti o n  c o nsta nt 
L D 5 0 
Me di a n l et hal d os e  
M C H  
Mea n c or p us c ul ar he mo gl o bi n  
M C V  
Mea n c or p us c ul ar v ol u me  
M D D  
Maj or de pr essi ve dis or der  
Me d D R A  
Me di cal Di cti o nar y f or Re gul at or y  Acti viti es 
M HI S  
M o difi e d Hac hi ns ki Is c he mi c  Scal e  
M M S E  
Mi ni -Me ntal State E xa mi nati o n  
M RI  
Ma gneti c Res o na nce I ma gi ng  
NI N C D S -A D R
D A  
Nati o nal I nstit ute  of Ne ur ol o gi cal a nd C o m mu ni cati ve  Dis eas es a nd 
Str o ke/ Al z hei mer's  Dis eas e a nd Rel ate d Dis or ders Ass oci ati o n  
N M D A  
N- met hyl - D-as parti c  aci d  
N O A E L  
N o o bs er ve d a d vers e effect l e vel  
N PI  
Ne ur o ps yc hi atri c  I nve nt or y  
P K  
P har mac o ki neti c  
P T  
Pr eferr e d ter m  
Q D, q d  
O nce dail y  
Q Tc F 
Fri deri ci a’s f or mul a c orr ecte d Q T i nter val  
S A E  
Seri o us a d vers e e ve nt  
S A P  
Statisti cal a nal ysis pl a n  
S O C  
S yste m  or ga n cl ass  
S U S A R  
S us pecte d une xpecte d  s eri o us a d vers e r eacti o n  
T E A E  
Tr eat me nt -e mer ge nt  a d vers e e ve nt 
U S A  
Unite d States of A meri ca  
 


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C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1  
I N T R O D U C TI O N 
1. 1  
B ac k gr o u n d 
S U V N -5 0 2  is pr o p os e d as a no vel, hi ghl y s el ecti ve a nd or all y acti ve a nta go nist  at a 
no n -peri p her al ce ntr al ner v o us s yste m s er ot o ni n r ece pt or, t he s er ot o ni n r ece pt or 
s ubt ype 6 ( 5-H T 6), i nte nde d f or t he tr eat me nt  of c o gniti ve dis or ders ass oci ate d wit h 
Al z hei mer’s dis eas e.  
1. 1. 1  Alz hei m er’s Dis e as e  
Al z he i mer’s dis eas e is a pr o gr essi ve a nd fatal ne ur o de ge ner ati ve  dis or der ma nifeste d  b y 
c o gniti ve a nd me mor y  deteri or ati o n i n a d diti o n t o pr o gr essi ve i mpair me nt  of acti viti es of 
dail y li vi ng . C urr e ntl y a vail a bl e tr eat me nts,  i ncl udi ng acet yl c holi nester as e i nhi bi t ors 
( d o ne pezil, ri vasti g mi ne, a nd gal a nta mi ne)  a nd no n-c o mpetiti ve  N-met hyl - D-as parti c 
aci d ( N M D A) r ece pt or bl oc kers ( me ma nti ne)  ar e s ee n as mi ni mall y  effecti ve, wit h o nl y 
mi nor s y mpt o mati c  i mpr o ve me nts  f or a li mite d d ur ati o n, a nd t he y d o not sl o w t he 
pr o gr essi o n of t he dis eas e.  
1. 1. 2  S u m m ar y of Fi n di n gs fr o m N o n -Cli ni c al St u di es  
1. 1. 2. 1  P h ar m ac ol o gy 
S U V N -5 0 2  a nd its meta b olite “ M 1 of S U V N- 5 0 2” s el ecti vel y bi nd t o 5-H T 6 r ece pt ors 
wit h i nhi biti o n c o nsta nt  ( Ki) val ues of 2. 1 6 a nd 1. 2 8 n M r es p ecti vel y, w he n teste d b y t he 
i n vitr o r a di o-li ga nd bi ndi ng  tec hni q ue  o n hu ma n  r ec o mbi na nt  5-H T 6 r ece pt ors. 
S U V N -5 0 2  a nd its meta b olite, M 1 of S U V N  5 0 2 , e xhi bite d a nta go nist-li ke  pr o perti es i n 
C R E -Luc ( cycli c a de nosi ne mo no p hos p hate  [ c A M P] r es p o ns e el e me nt-l ucifer as e) bas e d 
r e p orter gene  ass a y o n hu ma n  r ec o mbi na nt  5 -H T 6 r ece pt or, wit h diss oci ati o n c o nsta nt 
 w hi c h is i n a gr ee me nt  wit h val ues 
deter mi ne d b y r a di o -li ga nd bi ndi ng ass a y ( 2. 1 6 a nd 1. 2 8 n M r es pecti vel y) a nd s ho wi ng 
no detecta bl e a go nis t  acti vit y. 
S U V N -5 0 2  has s ho w n s el ecti vit y of 
 o ver a hundr e d  tar get 
sites i ncl udi ng ne ur otr a ns mitter  r el ate d r ece pt ors, e nz y mes,  pe pti des, gr o wt h 
fact ors/ hor mo nes,  i o n c ha nnels, ster oi ds, i m munol o gi cal  fact ors, s ec o nd mess e ngers, a nd 
pr osta gl a ndi ns.  
S U V N - 5 0 2  w as f o und  t o be acti ve i n t he no vel o bj ect r ec o gniti o n tas k ( e pis o di c 
me mor y),  i n  ti me -i nd uce d me mor y  disr upti o n as w ell as i n s c o p ol a mi ne -i nd uce d 
me mor y  disr upti o n . S U V N -5 0 2  w as f o und  t o e nha nce  c o gniti o n  i n t he  M orris w ater 
maze (s pati al me mor y)  i n b ot h a d ult a nd a ge d r ats. S U V N -5 0 2  w as f o und  t o r e vers e t he 
s c o p ol a mi ne-i nd uce d a mnesi a i n b ot h mo dels . T hus,  S U V N -5 0 2  acts vi a t he c holi ner gi c 
pat h w a y . I n t he passi ve a v oi da nce b o x ( e moti o nal me mor y), t her e w as a r e vers al i n t he 
ti me-i nd uce d me mor y  disr upti o n. S U V N -5 0 2  p ote nti ate d t he pr o -c o gniti ve effect of 
d o ne pezil hydr oc hl ori de ( H Cl) , a nd c o mbi ne d d o ne pezil H Cl a nd me ma nti ne H Cl 
tr eat me nt. S U V N - 5 0 2  w as f o und t o be s afe i n t he ce ntr al ner v o us s yste m, car di o vas c ul ar 
s yste m,  r es pir at or y, gastr oi ntesti nal a nd r e nal s afet y p har mac ol o gi cal st udi es at t he teste d 
d os es. 










S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
2  
S T U D Y  O B J E C TI V E S  
2. 1  
Pri mar y  O bj e cti ve  
T o e val ua te t he effi cac y of a 5-H T 6 a nta go nist,  S U V N-5 0 2  at dail y d os es of 5 0 mg or 
1 0 0 mg c o mpar e d  t o pl ace b o, as a dj unct tr eat me nt  i n s ubj ects wit h mo der ate Al z hei mer’s 
dis eas e  (Mi ni -Me ntal State E xa mi nati o n  [ M M S E ] s c or e of 1 2 t o 2 0) c urr e ntl y tr eate d 
wit h t he acet yl c holi nester as e i nhi bit or, d o ne pezil H Cl , a nd t he N M D A  a nta go nist, 
me ma nti ne  H Cl . Effi cac y will be  ass ess e d b y t he A D A S -C o g  after 2 6 w ee ks of 
tr eat me nt. 
2. 2  
Se c o n dar y O bj e cti ve(s)  
Sec o ndar y o bj ecti ve s of t he  st ud y  ar e:  
•  T o f urt her  e val uate t he effi cac y of t hes e tr eat me nts usi ng  t he  f oll o wi ng s cal es : 
- 
Cli ni cal De me nti a  Rati ng Scal e – S u m  of B o xes ( C D R -S B)  
- 
M M S E  
- 
Al z hei mer’s Dis eas e C o -o per ati ve St ud y  Acti vit y of Dail y Li vi ng ( A D C S -A D L)  
- 
N e ur o ps yc hi atri c  I nve nt or y  ( N PI)  1 2 ite m 
- 
C or nell Scal e f or De p r essi o n a nd De me nti a  ( C-S D D)  
•  T o e val uate t he s afet y a nd t her a pe uti c t ol er a bilit y of t hes e tr eat me nt s  usi ng A Es , 
l a b or at or y e val uati o ns, bl o o d pr ess ur e, E C Gs , p hysi cal a nd ne ur ol o gi cal e xa mi nati o n, 
a nd t he C ol u mbi a S ui ci de  Se verit y Rati ng Scal e ( C -S S R S)  
•  T o e val uate t he p har mac o ki neti cs  of S U V N -5 0 2  a d mi nister e d i n c o mbi nati o n  wit h 
d o ne pezil H Cl a nd me ma nt i ne  H Cl 
•  T o e xpl or e t he r el ati o ns hi p bet w ee n t he effi cac y of S U V N - 5 0 2  a nd a p oli p o pr otei n E 
( A P O-E) ge not ype ,  as w ell as a nal yze  s ubj ects mor e li kel y t o ha ve Al z hei mer’s 
dis eas e  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
3  
O V E R A L L  D E SI G N  A N D P L A N O F T H E S T U D Y  
3. 1  
O ve r vie w 
T his is a p has e 2 A, pr o of- of- c o nce pt, 2 6- w ee k , d o ubl e- bli nd, multice nter,  r a nd o mi ze d, 
par all el gr o up, pl ace b o -c o ntr oll e d st ud y  t o c o mpar e t he effi cac y a nd s afet y of tr eat me nt 
wit h  S U V N -5 0 2  ( 5 0 mg or 1 0 0 mg  q d) t o pl ace b o tr eat me nt  i n s ubj ects wit h mo der ate 
Al z hei mer ’s dis eas e r ecei vi ng d o ne pezil H Cl ( 1 0 mg q d ) a nd eit her me ma nti ne  H Cl 
( 10 mg t wi ce dail y  [ bid]) or Na me nda X R ®  ( 2 8 mg me ma nti ne  H Cl e xte nde d -r el eas e q d) 
or t he c o mbi nati o n t her a p y, Na mzari c ™ ( 2 8 mg me ma nti ne  H Cl e xte nde d -r el eas e / 
1 0 mg d o ne pezil H Cl) q d. 
T he st ud y  c o nsist s of a 2 t o 4- w ee k s cr ee ni ng peri o d, f oll o w e d b y a 2 6- w ee k d o ubl e-
bli nd tr eat me nt  peri o d a nd a 4 -w ee k si ngl e- bli nd pl ace b o w as ho ut peri o d  (Fi gur e 1 ). 
 
 
 
 
S U V N -5 0 2  5 0  m g q d  oral 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S U V N -5 0 2  1 0 0  m g q d  oral 
 
Pla c e b o  
q d  oral 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pla c e b o q d  oral 
 
 
 
 
 
 
 
 
 
 
 
 
D a ys  
D a y  -2 8 t o 
D a y  -1 4  
D a y 1  
We e k 4  
We e k 1 3  
We e k 2 6  
We e k 3 0  
 
 
 
 
 
 
 
Vi sit s 
1  
2  
3  
4  
5  
6  
 
Scre e nin g  
Ba s e line  
 
 
 
 
 
 
 
 
 
 
 
 
 
Tre at me nt perio d  
 
Was h o ut  perio d  
q d : o n ce d ail y 
Fi g ure  1 : St u dy  De si g n  
At t he s cr ee ni ng  visit , s ubj ects a nd t heir car e gi ve r or a p pr o pri ate l e gal r e pr es e ntati ve will 
si gn t he  i nf or me d  c o ns e nt  f or m pri or t o a ny pr oce d ur es . The i ncl usi o n a nd e xcl usi o n 
criteri a  will be r e vi e w e d i ncl udi ng de mo gr a p hi cs, me di cal hist or y a nd pri or a nd 
c o nc o mita nt  tr eat me nt,  NI N C D S -A D R D A  criteri a, M M S E, M o difi e d Hac hi ns ki 
Is c he mi c Scal e ( M HI S) , a nd C-S S R S . If  no m a gneti c r es o na nce ima gi ng  ( M RI ) or 
c o mp ute d  to mo gr a p hy  ( C T ) s ca n w as perf or me d wit hi n t he past 1 2 mo nt hs,  a M RI or C T 
s ca n will be perf or me d at s cr ee ni ng  t o c o nfir m  t hat  fi ndi ngs  ar e c o nsiste nt wit h t he 
di a gnosis of de me nti a d ue t o Al z hei mer’s dis eas e wit ho ut a ny ot her cli ni call y si gnifi ca nt 
c o mor bi d pat hol o gi es . S u bj ects will under go  p hysi cal a nd ne ur ol o gi cal e xa mi nati o n, 
bl o o d pr ess ur e ass ess me nt, el ectr ocar di o gr a m ( E C G ). Uri ne a nd bl o o d s a mpl e s will be 
c oll ecte d f or l a bor at or y e val uati o ns (i ncl udi ng  pr e gna nc y  test f or w o me n of c hil d beari ng 
p ote nti al) a nd pl as ma l e vels of d o ne pezil a nd me ma nti ne.  The A D A S -C o g  a nd C- S D D 
s c or es will als o be o btai ne d. 
T he bas eli ne visit will occ ur 1 4 t o 2 8 da ys after s cr ee ni ng . I ncl usi o n  a nd e xcl usi o n 
criteri a will be r e vi e w e d t o c o nfir m  eli gi bilit y of t he s ubj ect. S ubj ects will be e val uate d 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
f or A Es  a nd under go p hysi cal a nd ne ur ol o gi cal e xa mi nati o n,  bl o o d pr ess ur e ass ess me nt, 
a nd E C G. Uri ne a nd b l o o d s a mpl es will be c oll ecte d f or l a b or at or y e val uati o ns a nd 
A P O - E ge not ype  testi ng . Bas eli ne s c or es will be a ss ess e d f or t he M M S E, A D A S-C o g , 
C D R -S B , A D C S -A D L,  N PI, C -S D D a nd C -S S R S .  
F oll o wi ng c o nfir mati o n  of eli gi bilit y, s ubj ects will be r a nd o mi ze d i n a 1: 1: 1 r ati o t o o ne 
of t he f oll o wi ng t hr ee tr eat me nt  gr o ups:  
•  S U V N - 5 0 2  ( 5 0 mg) 
•  S U V N - 5 0 2  ( 1 0 0 mg) 
•  Pl ace b o  
Bli nde d S U V N -5 0 2/ pl ace b o t r eat me nt a nd ge neri c f or mul ati o ns  of d o ne pezil H Cl  1 0 mg 
a nd me ma nti ne  H Cl  1 0 mg  will be dis pe ns e d t o t he s ubj ects f or tr eat me nt  until t he ne xt 
visit.  
D uri ng  t he 2 6- w ee k tr eat me nt  peri o d, s ubj ects a nd car e gi vers will ha ve st ud y  visits at 
Wee k s 4, 1 3, a nd 2 6. At eac h of t hes e visit s, s ubj ects will be e val uate d f or A Es a nd 
under go  p hysi cal a nd ne ur ol o gi cal e xa mi nati o n,  bl o o d pr ess ur e ass ess me nt, a nd E C G. 
T he M M S E,  A D A S -C o g ,  C D R-S B , A D C S -A D L,  N PI, C -S D D a nd C -S S R S  s cor es will 
be ass ess e d . Uri ne a nd b l o o d s a mpl es f or l a b or at or y e val uati ons will be c oll ecte d at 
Wee ks  4 (li ver f uncti o n  tests o nl y), 1 3 a nd 2 6. F or w o me n of c hil d beari ng p ote nti al, a 
pr e gna nc y  test will be perf or me d at Wee k 2 6. Bl o o d s a mpl es f or pl as ma l e ve ls of 
S U V N - 5 0 2,  its meta b olite ( M 1 of S U V N- 5 0 2),  d o ne pezil a nd me ma nti ne will be 
c oll ecte d at Wee ks 4 a nd  2 6. 
S ubj ects w ho c o mpl et e t he 2 6-w ee k tr eat me nt  peri o d, will under go  a 4-w ee k si ngl e- bli nd 
pl ace b o w as ho ut peri o d . At Wee k 3 0, s ubj ects will atte nd a f oll o w-up  visit t o t he st ud y 
ce nter . D uri ng t his visit, s ubj ects will be e val uate d f or A Es a nd under go  p hysi cal a nd 
ne ur ol o gi cal e xa mi nati o n,  bl o o d pr ess ur e ass ess me nt, E C G, l a b or at or y e val uati o ns. T he 
C- S D D a nd C -S S R S  s c or es will be ass ess e d. 
S ubj ects w ho  dis c o ntinu e tr eat me nt  pr e mat ur el y (s ee S ecti o n 4. 3 ) s ho ul d  atte nd a fi nal 
visit si mil ar  t o Wee k 2 6 visit a nd, if s ubj ects a gr ee, t he s ubj ects will r et ur n 4 w ee ks l ater 
f or a f oll o w-up visit si mil ar t o Wee k  3 0 visit. 
D uri ng  t he c o urs e of t he st ud y,  a n i nde pe nde nt Data a nd Safet y M o nit ori ng  B oar d 
( D S M B) will be ass e mbl e d t o peri o di call y r e vi e w a nd e val uate acc u mul ate d  st ud y data 
f or s ubj ect s afet y, st ud y c o nd uct a nd pr o gr ess . T he D S M B will ha ve t he r es p o nsi bilit y t o 
ma ke r ec o m me ndati o ns  c o ncer ni ng  c o nti nuati o n,  mo difi cati o n, or ter mi nati o n  of t he 
st ud y. 
T he a p pr o xi mate bl o o d v ol u me t o be c oll ecte d d uri ng  t he st ud y is 1 3 5. 5 m L,  w it h  a 
ma xi mu m  of 2 6 m L  per visit.  
3. 2  
Crit e ri a f or E v al uati o n  of t he St u dy 
3. 2. 1  Pri m ar y Effi c acy Crit eri o n  
T he pri mar y criteri o n f or t he e val uati o n of effi cac y will be t he c ha nge  fr o m bas eli ne t o 
Wee k  2 6 i n A D A S -C o g   s c or e. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
3. 2. 2  Sec o n d ar y Effi c acy Crit eri a  
T he c ha nge  fr o m bas eli ne i n t he A D A S-C o g  s c or e will als o be ass ess e d at Wee ks 4 
a nd 1 3. 
Sec o ndar y effi cac y criteri a will als o  i ncl ude t he c ha nge  fr o m bas eli ne of t he f oll o wi ng 
vari a bl es : 
•  C D R -S B  at Wee ks  4, 1 3 a nd 2 6 
•  M M S E  at Wee ks  4, 1 3 a nd 2 6 
•  A D C S -A D L  at Wee ks  4, 1 3 a nd 2 6 
•  N PI  at Wee ks  4, 1 3 a nd 2 6 
•  C- S D D at Wee ks  4, 1 3 a nd 2 6 
3. 2. 3  S af et y Crit eri a  
Safet y e val uati o ns will i ncl ude t he r e p orti ng of A E s t hr o ugho ut  t he st ud y, bl o o d pr ess ur e 
meas ur e me nt , E C G s, p hysi cal a nd  ne ur ol o gi cal e xa mi nati o n,  a nd ass ess me nt of 
s ui ci dalit y usi ng  t he C- S S R S  at eac h visit.  
Bl o o d a nd uri ne s a mpl es f or l a bor at or y e val uati o ns will be c oll ecte d at s cr ee ni ng, 
bas eli ne a nd Wee ks 4 ( li ver f uncti o n  tests o nl y), 1 3, 2 6 a nd 3 0. 
3. 2. 4  Ot her Crit eri a  
At bas eli ne, a bl o o d s a mpl e will be dr a w n f or A P O - E ge not ype  testi ng.  
P l as ma s a mpl es will be a nal yze d f or l e vels of S U V N-5 0 2  a nd M 1 of  S U V N - 5 0 2,  at 
stea d y state ( Wee k 4 of tr eat me nt)  a nd at t he e nd of st ud y ( Wee k 2 6 of tr eat me nt) t o 
gat her  i nf or mati o n  o n p o p ul ati o n  p har mac o ki neti cs.  
Pl as ma s a mpl es will be a nal yze d f or l e vels of d o ne pezil a nd me ma nti ne  at s cr ee ni ng, at 
Wee k 4 of tr eat me nt  a nd at t he e nd of st ud y t o deter mi ne c o mpli a nce wit h st ud y 
me di cati o n.  
3. 3  
J ustific ati o n  of t he St u dy Desi g n  
T his st ud y  is desi gne d t o test t he hyp ot hesi s  t hat 5 0 mg  a nd 1 0 0 mg of S U V N - 5 0 2 
i mpr o ves t he c o gniti ve stat us of Al z hei mer's dis eas e s ubj ects w ho ar e c urr e ntl y r ecei vi ng 
d o ne pezil H Cl a nd me ma nti ne  H Cl , c o mpar e d t o pl ace b o. 
A ni mal t o xi c ol o gy da ta s up p ort t he s afet y of t he t w o d os a ge l e vels of S U V N-5 0 2,  5 0 mg 
a nd 1 0 0 mg  t o be us e d i n t his st ud y  a nd data fr o m  a p has e 1  si ngl e a nd multi pl e d os e 
st udi es s uggest  S U V N-5 0 2  s ho ul d be r el ati vel y s afe a nd w ell t ol er ate d i n s ubj ects wit h 
mo der ate Al z hei mer’s dis eas e  c urr e ntl y r ecei vi ng d o ne pezil H Cl a nd me ma nti ne  H Cl .  
T he desi gn of t his st ud y f oll o ws t he  r ec o m me ndati o ns  of t he  F o o d a nd Dr ug 
A d mi nistr ati o n  ( F D A  3 ) a nd t he E ur o pea n Me di ci ne A ge nc y  ( E M A  4 ) f or st udi es of s mall 
mol ec ul e s y mpt o mati c  dr ugs i n Al z hei mer’s dis eas e . T he st ud y  is d o ubl e- bli nd, 
pl ace b o -c o ntr oll e d a nd f oll o ws  a n a d d-o n desi gn t o t he sta ndar d - of-car e . Effi cac y 
ass ess me nts  i ncl ude c o gniti ve,  f uncti o nal  a nd gl o bal e val uati o ns usi ng  w ell -r ec o gni ze d 
s cal es. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
4  
S T U D Y  P O P U L A TI O N  
T he st ud y p o p ul ati o n will c o nsist of s ubj ects wit h  mo der ate Al z hei mer’ s dis eas e 
( M M S E 1 2- 2 0). S ubj ects a nd car e gi vers must  meet all t he i ncl usi o n criteri a a nd no ne of 
t he e xcl usi o n criteri a. 
4. 1  
I ncl usi o n  Crit e ri a 
S ubj ects must  meet all of t he f oll o wi ng i ncl usi o n criteri a t o be e nr oll e d i nt o t he  st ud y: 
1.  Mal e or fe mal e s ubj ects, a ge d bet w ee n 5 0 a nd 8 5 years i ncl usi ve at s cr ee ni ng. 
2.  Has a d i a gnosis of pr o ba bl e Al z hei mer’s dis eas e bas e d o n t he NI N C D S -A D R D A 
criteri a at l east 1 year pri or t o t he s cr ee ni ng visit.  
3.  Has a s c or e bet w ee n 1 2 a nd 2 0 i ncl usi ve o n t he M M S E at t he s cr ee ni ng a nd bas eli ne 
visits.  
4.  Has a M RI  or C T  s ca n perf or me d  wit hi n 1 2 mo nt hs  pri or t o s cr ee ni ng  wit h fi ndi ngs 
c o nsiste nt  wit h t he  di a gnosis of de me nti a  d ue t o Al z hei mer’s dis eas e  wit ho ut  a ny 
ot her cli ni call y si gnifi ca nt  c o mo r bi d pat hol o gi es. 
5.  Has a M HI S  s c or e  of 4 or l ess . 
6.  M ust be r ecei vi ng tr eat me nt  wit h  sta bl e d os es of d o ne pezil H Cl ( 1 0 mg q d), eit her as 
1 0 mg  d o ne pezil H Cl o nl y or part of t he c o mbi nati o n  t her a p y, Na mzari c ™ 
( 2 8 mg  me ma nti ne  H Cl e xte nde d -r el eas e / 1 0 mg d o ne p ezil H Cl ) q d f or at l east 3 
mo nt hs  pri or t o s cr ee ni ng  visit . S ubj ect s ar e li kel y t o  be mai ntai ne d  o n t his 1 0  mg 
dail y d os e of d o ne pezil H Cl or Na mzari c ™ f or t he e ntir e d ur ati o n  of t he st ud y. 
7.  M ust  be  r ecei vi ng tr eat me nt  wit h sta bl e d os es of me ma nti ne H Cl  ( 1 0 mg bi d) or 
Na me nda  X R ®  ( 2 8 mg me ma nti ne  H Cl e xte nde d -r el eas e q d) or as part of t he 
c o mbi nati o n t her a p y, Na mzari c ™ ( 2 8 mg  me ma nti ne  H Cl e xte nde d -r el eas e / 1 0 mg 
d o ne pezil H Cl ) q d f or at l east 3 mo nt hs pri or t o t he  s cr ee ni ng visit . S ubj ects ar e 
li kel y t o be mai ntai ne d o n t heir c urr e nt d os e of me ma nti ne  H Cl  or Na me nda  X R ®  or 
Na mzari c ™ f or t he d ur ati o n  of t he  st ud y. 
8.  A vail a bilit y of a pers o n ( car e gi ver) w ho i n t he i nvesti gat or's j ud g me nt  has fr e q ue nt 
a nd s uffi ci e nt  c o ntact  wit h t he s ubj ect, s uc h t hat  t his pers o n is q ualifi e d, willi ng a nd 
a bl e t o pr o vi de acc ur ate i nf or mati o n  r e gar di ng t he s ubj ect's c o gniti ve a nd f uncti o nal 
a biliti es a nd will acc o mpa ny  t he s ubj ect t o st ud y visits. T he car e gi ver s ho ul d ha ve 
face t o face c o ntact wit h t he s ubj ect f or a mi ni mu m  of a p pr o xi matel y 1 2 ho urs per 
w ee k s pr ea d o ver 3 t o 5 da ys d uri ng t he w ee k (f or e xa mpl e: 3 ho urs per da y f or 
4 da ys a w ee k , or 4 ho urs per da y f or 3 da ys a w ee k ). 
9.  M ust be li vi ng i n t he c o m munit y  or a n assiste d li vi ng facilit y . N o s ubj ects c urr e ntl y 
r esi di ng i n a nursi ng  ho me  or a nti ci pate d t o mo ve  i nt o a nursi ng  ho me  d uri ng  t he 
st ud y  will be all o w e d e ntr y  i nt o t he st ud y. 
1 0.  M ust be a mb ul at or y or a mb ul at or y  ai de d ( us e of ca ne or w al ker).  
1 1.  M ust  ha ve visi o n a nd heari ng ( c orr ecte d) s uffi ci e nt  t o c o mpl y  wit h t he testi ng 
pr oce d ur es. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
2 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1 2.  B ot h s ubj ect a nd car e gi ver must  be a bl e t o r ea d a nd understa nd E nglis h  or S pa nis h 
a nd ha ve a p pr o pri ate liter ac y s kills t o e ns ur e  c o mpli a nce wit h t he  testi ng  a nd st ud y 
visit pr oce d ur es.  
1 3.  Is not  pr e gna nt  or pl a nni ng  t o bec o me pr e gna nt  d uri ng  t he  st ud y. W o me n  of  
c hil d beari ng p ote nti al must ha ve  a ne gati ve pr e gna nc y  test at s cr ee ni ng a nd must  be 
usi ng or al or i nj ecta bl e c o ntr ace pti o n ( no n-c hil d beari ng p ote nti al is defi ne d as 
p ost -me no pa us al f or at l east 1 year or s ur gi cal sterili zati o n or hyster ect o my  at l east 
3 mo nt hs  bef or e st ud y  start).  
1 4.  S ubj ect ( or s ubj ect ’s l e gall y acce pta bl e r e pr es e ntati ve) a nd car e gi ver must  si gn a n 
I nf or me d  C o ns e nt  t o parti ci pate i n t he st ud y. 
4. 2  
E xcl usi o n  Crit e ri a  
S ubj ects w ho meet a ny of t he f oll o wi ng e xcl usi o n criteri a will not be all o w e d t o be 
r a nd o mi ze d  i nt o  t he  st ud y: 
1.  Has a  di a gnosis of de menti a d ue t o ot her ca us es, i ncl udi ng  v as c ul ar dis eas e, 
Par ki ns o n’s dis eas e, Le w y  B o d y d is eas e, AI D S, Cr e utzfel dt-J a ko b  dis eas e, 
fr o nt o-te mp or al de me nti a, H u nti ngt o n’s  dis eas e, maj or hea d tr a u ma,  pri mar y or 
s ec o ndar y cer e br al ne o pl asi a, or ot her no n- Al z hei mer  dis or ders . S ubj ects wit h maj or 
str o kes (l ar ge c orti cal/s ubc orti cal or i n br ai n ar eas r el ate d t o c o gniti o n), bas e d o n 
me di cal hist or y,  p hysi c al e xa m  or M RI, ar e e xcl ude d.  
2.  Has a  di a gnosis of s c hi z o p hr e ni a, bi p ol ar dis or der or c urr e nt maj or de pr essi ve 
dis or der ( M D D)  or s ubj ects w hos e C-S D D s c or es ar e s uggesti ve of pr o ba bl e 
de pr essi o n (t ypi call y s c or es ≥1 2). S ubj ects  wit h hist or y  of M D D  w ho ar e c urr e ntl y 
tr eate d a nd c o ntr oll e d o n me di cati o n f or at l east 6 mo nt hs ma y  be e nr oll e d . S ubj ect s 
ta ki ng  l o w d os es of a nti ps yc hoti cs f or t he tr eat me nt  of sl ee p dist ur ba nces or f or 
a gitati o n  or a ggr essi o n, f or w hi c h t he  d os e has bee n sta bl e f or at l east 1 mo nt h a nd 
not  a nti ci pate d t o c ha nge  d uri ng  t he c o urs e of  t he st ud y, ca n be e nr oll e d.  
3.  Is ta ki ng  c holi nester as e i nhi bit ors ot her t ha n  d o ne pezil H Cl, i ncl udi ng ri vasti g mi ne 
a nd gal a nta mi ne . S ubj ects c urr e ntl y  ta ki ng  5 mg  of d o ne pezil H Cl, or ta ki ng  2 3 mg 
dail y d os es of d o ne pezil H Cl or s ubj ects ta ki ng  1 0 mg  dail y d os e of d o ne pezil H Cl 
f or w ho m t he p hysi ci a n c o nte mpl ates  i ncr easi ng t he d os e t o 2 3 mg d uri ng  t he 
c o nd uct  of t he st ud y,  will not be e nr oll e d. 
4.  Is ta ki ng  d os es of me ma nti ne H Cl  ot her t ha n  1 0 mg bi d or Na me nda  X R ®  
( 2 8 mg  me ma nti ne  H Cl e xte nde d -r el eas e q d) or Na mzari c ™ ( 2 8 mg  me ma nti ne  H Cl 
e xte nde d -r el eas e / 1 0 mg d o ne pezil H Cl ) q d. 
5.  Has unc o ntr oll e d car di ac dis eas e or hyperte nsi o n . T his i ncl udes s ubj ects wit h hist or y 
of myocar di al i nfar cti o n wit hi n 6 mo nt hs  of s cr ee ni ng visit; c o ngesti ve heart fail ur e; 
hist or y  of unsta bl e  a ngi na  wit hi n 6 mo nt hs  of  s cr ee ni ng visit; a nd cli ni call y 
si gnifi ca nt  E C G at s cr ee ni ng visit a nd s ubj ects w hos e hyperte nsi o n  has not  bee n 
c o ntr oll e d o n me di cati o n f or at l east 3 mo nt hs  pri or t o s cr ee ni ng. 
6.  Has a hist or y or c urr e nt  e vi de nce of l o ng  Q T s yndr o me, Fri deri ci a’s f or mul a 
c orr ecte d Q T ( Q Tc F) i nter val ≥ 4 7 0 ms (f or mal e s ubj ects) or ≥ 4 8 0 ms (f or fe mal e 


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s ubj ects), or t ors a des de p oi ntes, as deter mi ne d b y a n E C G r ea d b y a ce ntr al  E C G 
ve nd or. 
7.  Has  br a d ycar di a ( < 5 0  b p m) or tac hycar di a ( > 1 0 0  b p m) o n t he E C G at s cr ee ni ng.  
8.  Has  unc o ntr oll e d  T ype - 1 or T ype - 2 di a betes (gl ycate d he mo gl o bi n  [ H b A 1c] 
a b o ve 6. 5 %). A S ubj ect  wit h H b A 1c l e vels up t o 7. 5 % ca n be e nr oll e d if t he 
i nvesti gat or beli e ves t he s ubj ect’s di a betes is under c o ntr ol.  
9.  Has  ca ncer or a mali gna nt  t u mor, or has bee n tr eate d f or a n acti ve mali gna nc y  wit hi n 
t he past 5 years. S ubj ects wit h sta bl e untr eate d pr ostate ca ncer,  l ocali ze d s q ua mo us 
cell ca ncer or bas al cell ca ncer wil l be all o w e d. 
1 0.  Has  untr eate d t hyr oi d dis or der . S ubj ects  w ho ar e c o nsi der e d e ut hyr oi d  o n me di cati o n 
wit h nor mal fr ee t hyr o xi ne  (T 4 ) will be all o w e d.  
1 1.  Has a h ist or y of s ei z ur e dis or der. 
1 2.  Has  cli ni call y si gnifi ca nt  r e nal or he pati c i mpair me nt.  
1 3.  Has  a ny cli ni call y si gnifi ca nt  a b nor mal l a b or at or y val ues. S ubj ects wit h li ver 
f uncti o n  tests (as partate a mi notr a nsfer as e [ A S T ] or al a ni ne a mi notr a nsfer as e [ A L T ]) 
gr eater t ha n  t wi ce t he up per li mit of nor mal will be  e xcl ude d. 
1 4.  Is tr eate d or li kel y t o r e q uir e tr eat me nt  d uri ng t he st ud y,  wit h a ny  me di cati o ns 
pr o hi bite d b y t he st ud y pr ot oc ol.  
1 5.  Has  a b nor mal vita mi n B- 1 2 l e vels t hat ar e l o w er t ha n  nor mal limit s a nd r e mai ns l o w 
o n r e peat testi ng.  S ubj ects ta ki ng  vita mi n  B -1 2 s up pl e me nts  w ho ar e wit hi n nor mal 
li mits or a b o ve at s cr eeni ng  or wit hi n nor mal li mits  or a b o ve at r e peat testi ng will be 
all o w e d. 
1 6.  Has  parti ci pate d i n a pr e vi o us cli ni cal st ud y wit hi n 2 6 w ee ks of t he s cr ee ni ng  visit , or 
has  bee n pr e vi o usl y tr eate d wit h t he i nvesti gati o nal pr o d uct, S U V N- 5 0 2. 
1 7.  S ubj ect ( or car e gi ver)  is dee me d ot her wis e i neli gi bl e f or parti ci pati o n i n t his st ud y i n 
t he i nvesti gat or’s j ud g me nt. 
1 8.  Is at i m mi ne nt  ris k of s elf-har m, bas e d o n cli ni cal i nter vi e w a nd r es p o ns es o n t he 
C- S S R S, or of har m t o ot hers i n t he o pi ni o n of t he I nvesti gat ors. S ubj ects mu st  be 
e xcl ude d if t he y  r e p ort s ui ci dal i deati o n wit h i nte nt,  wit h or wit ho ut  a pl a n or met ho d 
( e. g. p ositi ve r es p o ns e t o Ite ms  4 or 5 i n ass ess me nt of s ui ci dal i deati o n o n t he 
C- S S R S) i n t he past 2 mo nt hs,  or s ui ci dal be ha vi or i n t he past 6 mo nt hs. 
4. 3  
S u bj e ct  Wit h dr a w a l  a n d  Re pl ace  me nt  
S ubj ect s a nd car e gi vers ma y  wit hdr a w fr o m  t he e ntir e st ud y i ncl udi ng f oll o w-up  at a ny 
ti me  wit ho ut  pe nalt y a nd f or a ny r eas o n wit ho ut  pr ej udi ce t o his or her f ut ur e  me di cal 
car e. 
S ubj ect s must  be wit hdr a w n fr o m st u dy  dr ug under t he f oll o wi ng cir c u msta nces: 
•  Pr e gna nc y  (s ee Secti o n 6. 2. 1. 7 ) 
•  El e vate d A L T, A S T, or t otal bilir ubi n (s ee Secti o n 6. 2. 2 ) 
•  S ui ci dal i deati o n or be ha vi or (s ee Secti o n 6. 2. 6. 1 ) 


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•  Tr eat me nt  wit h pr o hi bite d c o nc o mita nt  me di cati o ns is r e q uir e d (s ee Secti o n 5. 7. 2 ) 
•  Tr eat me nt  wit h  d o ne pezil H Cl ca nnot be mai ntai ne d  at t he d os e of 1 0 mg q d or as 
part of t he c o mbi nati o n  t her a p y of Na mzari c ™ ( 2 8 mg me ma nti ne  H Cl e xte nde d-
r el eas e / 1 0 mg d o ne pezil H Cl) q d. 
•  Tr eat me nt  wit h me ma nti ne  H Cl ca nnot be mai ntai ne d  at eit her 1 0 mg bi d of 
me ma nti ne  H Cl or 2 8 mg me ma nti ne  H Cl e xte nde d-r el eas e q d of Na me nda  X R ®  or 
as part of t he c o mbi nati o n  t her a p y of Na mzari c ™ ( 2 8 mg me ma nti ne  H Cl e xte nde d-
r el eas e / 1 0 mg d o ne pezil H Cl) q d 
•  S ubj ect’s no nc o mpli a nce  t o st ud y tr eat me nt  (s ee Secti o n 5. 6 ) 
•  A me di cal c o nditi o n or pers o nal cir c u msta nce w hi c h, i n t he o pi ni o n of t he 
I nvesti gat or  a nd/ or S p o ns or, pl aces t he s ubj ect at unnecess ar y  ris k t hr o ugh  c o nti nue d 
parti ci pati o n i n t he  st ud y or d oes not all o w t he s ubj ect t o a d her e t o t he r e q uir e me nts 
of t he pr ot oc ol  
S ubj ect s ma y be r e q uir e d t o wit hdr a w fr o m  st ud y  dr ug, acc or di ng t o t he I nvesti gat or’s 
j ud g me nt, f or t he f oll o wi ng r eas o ns: 
•  A E (s) 
•  A ny  r eas o n at  t he dis cr eti o n of t he I nvesti gat or 
I n all cas es, t he r eas o n(s) f or wit hdr a w al, a nd t he pri mar y r eas o n, must  be r ec or de d o n 
t he el ectr o ni c Cas e Re p ort F or m ( e C R F). If a s ubj ect is pr e mat ur el y  wit hdr a w n fr o m  t he 
st ud y  dr ug  f or a ny  r eas o n, t he  I nvesti gat or must  ma ke e ver y eff ort t o perf or m t he 
e val uati o ns des cri be d f or t he Wee k 2 6 visit a nd a f oll o w- u p visit 4  w ee ks l ater . 
If a s ubj ect wit hdr a ws c o ns e nt  a nd still a gr ees t o under go  a fi nal e xa mi nati o n,  t his will 
be d oc u me nte d  o n t he e C R F a nd t he I nvesti gat or’s c o p y of t he i nf or me d c o ns e nt  f or m 
(I C F), w hi c h will be c o untersi gne d  a nd date d b y  t he s ubj ect.  
A s ubj ect ma y als o be wit hdr a w n  fr o m  st ud y  dr ug b y t he S p o ns or, Re gul at or y 
A ut horiti es , or I nde pe nde nt  Et hi cs C o m mittees (I E Cs)/I nstit uti o nal  Re vi e w B oar ds 
(I R Bs). 
S ubj ect s will also be wit hdr a w n if t he e ntir e st ud y is ter mi nate d  pr e mat ur el y as des cri be d 
i n Secti o n 9. 1 1 . 
Wit hdr a w n s ubj ects will not be r e pl ace d . If t he car e gi ver wit hdr a ws c o ns e nt, t he 
i nvesti gat or s ho ul d c o ns ult wit h t he S p o ns or/ Me di cal M o nit or r e gar di ng p ote nti al 
r e pl ace me nt of t he car e gi ver. 
4. 4  
Pl a n ne d  S a m ple   Siz e  a n d  N u m be r  of St u dy  Ce nt e rs  
It is pl a nne d t o r ecr uit 5 3 7 s ubj ects at a p pr o xi matel y  9 0 ce nters i n t he Unite d  States of 
A meri ca ( U S A) f or t his st ud y. See Secti o n  8. 9  f or a dis c ussi o n of s a mpl e si ze. 
4. 5  
S u bj e ct  I de ntific ati o n  a n d  R a n do miz ati o n 
4. 5. 1  S u bj ect  I de ntifi c ati o n 
After i nf or me d c o ns e nt  is o btai ne d , eac h s ubj ect will r ecei ve a uni q ue s cr ee ni ng nu mber . 
E nr oll e d s ubj ects w ho dr o p o ut of t he st ud y bef or e r a nd o mi zati o n  will r etai n t heir 
s cr ee ni ng  nu mber. T he s cr ee ni ng nu mber  f or eac h s ubj ect will be a 6-di git i de ntifi cati o n 


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nu mber  s uc h t hat all pati e nts fr o m a ce nter ar e gi ve n c o ns ec uti ve i de ntifi cati o n nu mber 
i n s uccessi ve or der of i ncl usi o n. T he first 3 di git s of t he  s cr ee ni ng  nu mber  will be t he 
desi gnate d i nvest i gat or ce nter nu mber  a nd t he l ast 3 di gits will be assi gne d at t he 
i nvesti gat or ce nter ( e. g., t he t hir d pati e nt at ce nter 5 w o ul d be gi ve n t he nu mber  0 0 5 0 0 3). 
4. 5. 2  R a n d o miz ati o n Sc he m e  
Eli gi bl e s ubj ects will be r a nd o mi ze d t o r ecei ve o ne of t he t hr ee tr eat me nts:  S U V N - 5 0 2 
5 0 mg,  S U V N -5 0 2  1 0 0  mg, or pl ace b o i n a 1: 1: 1 r ati o, usi ng per mute d  bl oc ke d 
r a nd o mi zati o n. 
4. 5. 3  All oc ati o n/ R a n d o miz ati o n of S u bj ect s t o Tr e at m e nt 
Ra nd o mi zati o n  of s ubj ect t o tr eat me nt  will occ ur at bas eli ne ( Visit 2)  after all s cr ee ni ng 
pr oce d ur es ha ve bee n perf or me d a nd eli gi bilit y f or t he st ud y c o nfir me d . Eac h 
r a nd o mi ze d s ubj ect will r ecei ve a uni q ue r a nd o mi zati o n  nu mber .  Ra nd o mi ze d s ubj ects 
w ho ter mi nate  t heir st ud y parti ci pati o n f or a ny r eas o n, r e gar dl ess of w het h er st ud y  dr ug 
w as ta ke n or not, will r et ai n t heir r a nd o mi zati o n  nu mber.  
F or t he r a nd o mi zati o n  of s ubj ects, t he I nvesti gat or will us e a n I nter acti ve Voi ce 
Res p o ns e S yste m (I V R S) . Details ca n be f o und  i n t he st ud y  fil e . I V R S  will assi gn 
s ubj ects i n a d o ubl e-bli nd ma nner t o a tr eat me nt  gr o up bas e d o n t he pr e- defi ne d 
r a nd o mi zati o n  list. 


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5  
S T U D Y  D R U G  
5. 1  
I de ntit y 
5. 1. 1  I nvesti g ati o n al Tr e at m e nt: S U V N-5 0 2 a n d M at c hi n g Pl ace b o  
Fr o m Da y 1 t o t he e nd of Wee k 2 6, e li gi bl e s ubj ects will r ecei ve d o ubl e- bli nd or al 
a d mi nistr ati o n of o ne of f oll o wi ng t hr ee tr eat me nts: 
•  S U V N - 5 0 2  5 0 mg 
•  S U V N - 5 0 2  1 0 0 mg 
•  pl ace b o  
D uri ng  t he si ngl e- bli nd pl ace b o w as ho ut peri o d ( Wee ks 2 7 t o 3 0), all s ubj ects will 
r ecei ve pl ace b o. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1. 2  Ot her St u dy Dr u gs  
I n a d diti o n t o t he i nvesti gati o nal dr ug, all s ubj ects will als o c o nti nue  t o r ecei ve  dail y 
a d mi nistr ati o ns  of t he f oll o wi ng tr eat me nts  t hr o ugho ut  t he  st ud y (i ncl udi ng  t he 
si ngl e- bli nd pl ace b o w as ho ut peri o d) : 
•  d o ne pezil H Cl 1 0 mg  q d 
A N D  
•  me ma nti ne  H Cl 1 0 mg  bi d or Na me nda X R ®  ( 2 8 mg me ma nti ne  H Cl e xte nde d-
r el eas e) q d 
O R  
•  Na mzari c ™ ( 2 8 mg  me ma nti ne  H Cl e xte nde d-r el eas e / 1 0 mg  d o ne pezil H Cl ) q d. 
5. 2  
A d mi nist r ati o n  
5. 2. 1  I nvesti g ati o n al Tr e at m e nt: S U V N-5 0 2 a n d M at c hi n g Pl ace b o  
Eac h ta bl et of  S U V N-5 0 2  5 0 mg,  S U V N - 5 0 2  1 0 0 mg a nd matc hi ng  pl ace b o will c o ntai n 
t he dail y d os e t o be a d mi nister e d t o t he s ubj ects. 


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Tr eat me nt  will start after t he bas eli ne visit w her e s ubj ects a nd car e gi vers will be 
pr o vi de d wit h t he nu mber  of ta bl ets nee de d un til t he  ne xt  visit. 
O n da ys wit h no s c he d ul e d st ud y  visits , subj ects will ta ke o ne ta bl et per da y i n t he 
mor ni ng,  wit h a gl ass of w ater ( wit h or wit ho ut  f o o d) .  
O n t he  da y  of t he  st ud y  visits, s ubj ects will be i nstr ucte d  not t o ta ke t heir tr eat me nt  at 
ho me , as tr eat me nt  will be dis pe ns e d at t he st ud y  ce nter.  
5. 2. 2  Ot her St u dy Dr u gs  
D o ne pezil H Cl  ( 1 0 mg  q d), me ma nti ne  H Cl ( 1 0 mg  bi d) a nd Na me nda X R ®  ( 2 8 mg 
me ma nti ne  H Cl e xte nde d -r el eas e q d) or Na mzari c ™ ( 2 8 mg me ma nti ne  H Cl e xte nde d-
r el eas e / 1 0 mg d o ne pezil H Cl) q d s ho ul d be a d mi nister e d at sta bl e d os es t hr o ugho ut  t he 
st ud y at t he s a me ti me e ver y da y, as dir ecte d b y t heir pr es cri bi ng p hysi ci a n. 
Ge neri c f or mul ati o n s  of d o ne pezil H Cl ( 1 0 mg) a nd me ma nti ne  H Cl ( 1 0 mg) will be 
pr o vi de d b y t he S p o ns or  a nd dis pe ns e d t o t he s ubj ects fr o m bas eli ne .  
S ubj ects tr eate d wit h Na me nda X R ®  or Na mazari c ™ will  c o nti nue  t o ta ke  t heir o w n 
me di cati o n  as dir ecte d  b y t heir pr es cri bi ng p hysi ci a n.  
A ny cess ati o n of t hes e me di cati o ns, if r ec o m me nde d  b y t he pers o nal p hysi ci a n, must  be 
r e p orte d i m me di atel y  t o t he I nvesti gat or a nd t he S p o ns or/ Me di cal M o nit or f or 
c o ns ultati o n.  
S ubj ects r e q uiri ng d os e mo difi cati o ns f or d o ne pezil H Cl or me ma nti ne  H Cl  will be 
wit hdr a w n.  
O n t he  da y of t he  st ud y  visits, s ubj ects  s ho ul d not  ta ke t hei r tr eat me nt  at ho me,  as 
tr eat me nt  will be dis pe ns e d at t he st ud y ce nter. 
5. 3  
P ac k a gi ng, L a beli ng a n d  St or a ge  
5. 3. 1  I nvesti g ati o n al Tr e at m e nt: S U V N-5 0 2 a n d M at c hi n g Pl ace b o  
S U V N -5 0 2  will be s up pli e d as i de nti call y a p peari ng ta bl ets t hat c o ntai n eit her 5 0 mg or 
1 0 0 mg  of S U V N - 5 0 2. Pl ace b o ta bl ets matc hi ng  S U V N - 5 0 2  ta bl ets will als o be s up pli e d. 
S U V N -5 0 2  5 0  mg,  S U V N -5 0 2  1 0 0  mg a nd matc hi ng  pl ace b o will be pr o vi de d i n b ottl es 
c o ntai ni ng 3 5 ta bl ets. T he st ud y  dr ugs  will be pac ka ge d b y t he S p o ns or  acc or di ng t o all 
l ocal l e gal r e q uir e me nts. St ud y  dr ug will be l a bel e d i n acc or da nce wit h a p pli ca bl e 
r e gul at or y  r e q uir e me nts. 
All s up pli es must  be st or e d i n acc or da nce wit h t he ma nufact ur er’s  i nstr ucti o ns or i n 
acc or da nce wit h U S P C o ntr oll e d R o o m Te mper at ur e  ( 2 0– 2 5° C [ 6 8 – 7 7° F] wit h 
e xc ursi o ns per mitte d bet w ee n 1 5 a nd 3 0° C [ 5 9  – 8 6° F]). Until dis pe ns e d t o t he s ubj ects, 
t he st ud y  dr ug will be st or e d i n a s ec ur el y l oc ke d ar ea, accessi bl e t o a ut hori ze d  pers o nnel 
o nl y.  
5. 3. 2  Ot her St u dy Dr u gs  
Ge neri c f or mul ati o ns  of d o ne pezil H Cl ( 1 0 mg) a nd me ma nti ne  H Cl ( 1 0 mg) will be 
pr o vi de d b y t he S p o ns or i n t heir c o m mer ci all y a vail a bl e pac ka gi ng  wit h t h e l a bel ‘f or 
cli ni cal tri al us e  o nl y’ . 


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5. 4  
Bli n di ng  a n d  Bre a ki ng  t he  Bli n d  
T he st ud y will be perf or me d i n a d o ubl e- bli nd ma nner . S U V N- 5 0 2  will be s up pli e d as 
i de nti call y a p peari ng ta bl ets t hat c o ntai n eit her 5 0 mg or 1 0 0 mg  of  S U V N - 5 0 2. Pl ace b o 
ta bl ets matc hi ng  S U V N- 5 0 2  ta bl ets will als o be s up pli e d. Ta bl ets will be si mil ar i n c ol or, 
s mell, taste, a nd a p pear a nce, t her e b y e na bli ng d o uble- bli nd c o nditi o ns.  
T he st ud y  bli nd s ho ul d  not be br o ke n  e xce pt i n a me di cal e mer ge nc y  ( w her e kno wl e d ge 
of t he st ud y dr ug r ecei ve d w o ul d affect t he tr eat me nt  of t he e mer ge nc y)  or r e gul at or y 
r e q uir e me nt. 
T he bli nd must  o nl y  be br o ke n  f oll o wi ng dis c ussi o n o n  a cas e - b y-cas e basis, at t he 
dis cr eti o n of t he S p o ns or/ Me di cal M o nit or. 
If t he bli nd is br o ke n, t he date, ti me, a nd r eas o n must  be r ec or de d i n t he s ubj ect’s e C RF, 
a nd a ny ass oci ate d A E r e p ort.  
T he I nvesti gat or  s ho ul d notif y  t he S p o ns or/ Me di cal M o nit or pri or t o c o ntacti ng  I V R S. 
All calls r es ulti ng  i n a n unbli ndi ng  e ve nt will be r ec or de d a nd r e p orte d b y t he I V R S  t o 
t he C R O Me di cal M o nit or a nd t he S p o ns or .  
T he D S M B will ha ve access t o t he r a nd o mi zati o n  c o de, a nd t he c o de f or a parti c ul ar 
s ubj ect ma y be dis cl os e d after a p pr o pri ate dis c ussi o n wit h t he S p o ns or .  
If a n I nvesti gat or,  site pers o nnel perf or mi ng  ass ess me nts, or s ubj ect, is unbli nde d, t he 
s ubj ect must  be liste d as maj or pr ot oc ol de vi ati o n. H o w e ver, t he s ubj ect will not be 
wit hdr a w n fr o m st ud y  tr eat me nt .   
Seri o us une xpecte d  s us pecte d a d vers e r eacti o ns ( S U S A Rs), w hi c h ar e s ubj ect t o 
e xpe dite d r e p orti ng, s ho ul d be unbli nde d bef or e s ub missi o n t o t he Re gul at or y 
A ut horiti es  
T he o ver all r a nd o mi zati o n  c o de will be br o ke n o nl y f or r e p orti ng t he  fi nal r es ults of t he 
st ud y. T his will occ ur o nce all fi nal cli ni cal data ha ve  bee n e nter e d o nt o t he data bas e, all 
data q ueri es ha ve bee n r es ol ve d, t he assi gn me nt  of s ubj ect s t o t he  a nal ysis s ets has bee n 
c o mpl ete d , t he  S A P has bee n fi nali ze d a nd t he data bas e has bee n l oc ke d . 
5. 5  
Dr ug  Acc o u nt a bilit y  
T he I nvesti gat or  is r es p o nsi bl e f or mai ntai ni ng  acc ur ate st ud y  dr ug  acc o unta bilit y 
r ec or ds t hr o ugho ut  t he st ud y. 
Eac h dis pe nsi ng of st ud y  dr ug  will be d oc u me nte d  i n t he e C R F. 
T he I nve sti gat or is r es p o nsi bl e f or r et ur ni ng  all unus e d  or parti all y us e d st ud y  dr ug  t o t he 
S p o ns or or S p o ns or’s desi gnee a nd must  verif y t hat  all unus e d  or parti all y us e d dr ug 
s up pli es ha ve bee n r et ur ne d b y t he s ubj ect a nd t hat no r e mai ni ng  s up pli es ar e i n t he 
Investi gat or’s p oss essi o n.  
5. 6  
C o m pli a nce  
N ote t hat  t he  car e gi ver is r es p o nsi bl e f or hol di ng,  dis pe nsi ng,  a nd r et ur ni ng  st ud y  dr ugs 
a nd f or o vers eei ng all me di cati o ns.  
As part of t he r o uti ne  r ec or di ng of t he  a mo unt  of st ud y  me di cati o n (i ncl udi ng  S U V N- 5 0 2 
or pl a ce b o ta bl ets, d o ne pezil H Cl , a nd me ma nti ne  H Cl  if pr o vi de d b y t he S p o ns or) ta ke n 
b y eac h s ubj ect, t he car e gi ver  will r et ur n st ud y me di cati o n at eac h cli ni c visit, i ncl udi ng 


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e mpt y  b ottl es ( be gi nni ng  at Visit 3) a nd t he nu mber  of ta bl ets r e mai ni ng  i n t he st ud y 
pac ka gi ng  will be c o unte d a nd r ec or de d . T hes e r es ults will be us e d t o cal c ul ate s ubj ect 
c o mpli a nce . I nsta nces  w her e t he s ubj ect t o o k mor e or l ess st ud y me di cati o n t ha n 
pr es cri be d will be r ec or de d o n t he e C R F .  
T o mo nit or  f or p ote nti al f or mis us e, t he site will d oc u me nt  si gnifi ca nt dis cr e pa nci es i n 
dr ug  r et ur ns w her e  t he car e gi ver r et ur ns l ess st ud y me di cati o n t ha n  e xpecte d b ut de ni es 
ta ki ng  e xtr a st ud y me di cati o n ( e. g., l ost or missi ng me di cati o n e q ui val e nt t o mor e t ha n 
o ne ta bl et per w ee k).  
I n a d ditio n t o r o uti ne s ur veill a nce of s ubj ect st ud y me di cati o n c o mpli a nce, 
s ubj ects/ car e gi vers will be gi ve n st ud y  dr ugs “cal e ndar sl ee ves ” w hi c h affi x t o t he 
e xteri or of st ud y me di cati o n b ottl es t o hel p s ubj ects r e me mber w he n t o ta ke st ud y 
me di cati o n . T hes e sl ee v es will als o hel p s ubj ect/ car e gi ver t o r e me mber w he n t he s ubj ect 
miss e d a d os e . T hes e sl ee ves will be pr o vi de d t o t he site a nd t he site will sli de t he m  o nt o 
t he b ottl es. T he site w ill t he n i nstr uct t he car e gi ver o n ho w t o ma ke  t he m  s ubj ect -s pecifi c 
(i.e., d oc u me nt  o n t he “cal e ndar sl ee ve” t he date t o start ta ki ng st ud y me di cati o n,  b ottl e 
nu mber).  
W he n  t he s ubj ect/ car e gi ver r et ur ns t o t he cli ni cal site, t he site will perf or m a ta bl et c o unt 
a nd als o r e vi e w t he “cal e ndar  sl ee ve” t o verif y ta bl et c o unt  a nd a ny p ossi bl e miss e d or 
e xtr a d os es ta ke n. If t her e is a dis cr e pa nc y bet w ee n t he b ottl e a nd t he “cal e ndar sl ee ve” 
s ubj ect/ car e gi ver ver bal acc o unt  will be t he fi nal decisi o n f or w hi c h t o d oc u me nt  i n t he 
e C R F. Dis cr e pa nci es s ho ul d be d oc u me nte d  i n t he site’s s o u r ce d oc u me nts  a nd t he 
r eas o ni ng f or w hat w as ulti matel y  r ec or de d i n t he e C R F. 
F or s ubj ects w ho dis c o nti nue  st ud y  me di cati o n earl y b ut r e mai n i n t he st ud y,  site 
pers o nnel s ho ul d e ns ur e t he  s ubj ect r et ur ns  all st ud y me di cati o n  at t he earl y ter mi nati o n 
visit . S ubj ects a nd car e gi vers will als o be r e mi nde d t o c o nti nue  bac kgr o und  t her a p y f or 
Al z hei mer’s dis eas e ( d o ne pezil H Cl a nd me ma nti ne  H Cl).  
A d mi nistr ati o n  of st ud y  dr ugs will be wit ness e d b y t he I nvesti gat or a nd/ or st ud y staff at 
eac h visit. All ot her st ud y tr eat me nts s ho ul d be a d mi nister e d b y t he s ubj ect at ho me  ( w it h 
assista nce fr o m t he car e gi ver , as nee de d). 
C o mpli a nce wit h d o ne pezil H Cl  a nd me ma nti ne  H Cl  tr eat me nt  will als o be ass ess e d b y 
meas uri ng  dr ug l e vels i n pl as ma s a mpl es c oll ecte d at s cr ee ni ng, Wee k 4 a nd Wee k 2 6.  
S ubj ects s ho wi ng l ess  t ha n  8 0 % c o mpli a nce t o a ny  st ud y  tr eat me nt  (i ncl udi ng 
S U V N -5 0 2  or pl ace b o ta bl ets, d o n e pezil H Cl , a nd me ma nti ne  H Cl  if pr o vi de d b y t he 
S p o ns or) f or t w o c o ns ec uti ve visits will be wit hdr a w n fr o m t he st ud y.  
5. 7  
Pre vi o us a n d  C o nc o mit a n t  Me dic ati o ns 
5. 7. 1  Per mitt e d C o nc o mit a nt M e di c ati o ns  
A ny  me di cati o n  t he s ubj ect ta kes ot her t ha n  t he st ud y  dr ug, i ncl udi ng  her bal a nd ot her 
no n -tr a diti o nal r e me di es, is c o nsi der e d a c o nc o mita nt  me di cati o n. All c o nc o mita nt 
me di cati o ns must be r ec or de d  i n t he e C R F. T he f oll o wi ng i nf or mati o n  must  be r ec or de d 
i n t he e C R F f or eac h c o nc o mita nt  me di cati o n: ge neri c na me, r o ute of a d mi nistr ati o n, 
start date, st o p date, d os a ge, a nd i ndi cati o n. A ny  c ha nges  i n t he d os a ge or r e gi me n  of  a 
c o nc o mita nt  me di cati o n mus t  be r ec or de d i n t he e C R F. 


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At Scr ee ni ng, s ubj ects will be as ke d w hat me di cati o ns t he y  ha ve ta ke n  d uri ng t he l ast 
3 mo nt hs . At eac h s ubs e q ue nt  st ud y  visit, s ubj ects will be as ke d w hat c o nc o mita nt 
me di cati o ns  t he y  ar e c urr e ntl y  ta ki ng.  
5. 7. 2  Pr o hi bit e d C o nc o mit a nt  M e di c ati o ns 
Str o ng i nhi bit ors of C Y P 3 A 4, i ncl udi ng pr oteas e i nhi bit ors ( ataza na vir, i ndi na vir, 
rit o na vir, s a q ui na vir, nelfi na vir), az ol e a ntif ungals  ( ket oc o naz ol e,  itr ac o naz ol e, 
fl uc o naz ol e), macr oli de a nti bi oti cs ( er yt hr o myci n,  cl arit hr o myci n,  telit hr o myci n), 
cal ci u m c ha nnel bl oc kers ( ver a pa mil a nd dilti aze m)  a nd gr a pefr uit j ui ce ar e pr o hi bite d 
d uri ng  t he  st ud y . 
Str o ng i nd ucers of C Y P 3 A 4, i ncl udi ng  rifa mpi ci n, p he nyt oi n,  p he no bar bital, 
car ba maze pi ne, de xa met has o ne  a nd St. J o hn’s W ort ( her bal s up pl e me nt) ar e pr o hi bite d 
d uri ng  t he  st ud y .  
S ubj ects r e q uiri ng tr eat me nt  wit h pr o hi bite d c o nc o mita nt  me di cati o ns s ho ul d be 
wit hdr a w n fr o m t he  st ud y. 


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V A RI A B L E S  A N D M E T H O D S  O F A S S E S S M E N T  
6. 1  
Effic ac y V ari a ble s 
It is str o ngl y r ec o m me nde d  t hat o ne r ater is assi gne d f or eac h s ubj ect f or eac h of t he 
effi cac y ass ess me nt s cal es des cri be d bel o w, s o t hat o ne r ater s c or es a s ubj ect’s 
ass ess me nt f or t he e ntir e st ud y.  F or e xa mpl e, t he r ater assi gne d t o perf or m t he M M S E 
w o ul d r ate t hat s cal e f or all visits f or t hat s ubj ect. 
6. 1. 1  Pri m ar y Effi c acy V ari a bl e 
T he pri mar y effi cac y vari a bl e f or t he  st ud y  is t he  A D A S-C o g . 
T he A D A S -C o g  is a bri ef meas ur e of c o gniti o n, i ncl udi ng  w or d r ecall, c o m ma nds, 
c o nstr ucti o nal pr a xis, na mi ng  o bj ects a nd fi ngers, i deati o nal pr a xis, ori e ntat i o n, w or d 
r ec o gniti o n,  r e me mberi ng  test i nstr ucti o ns,  s p o ke n l a ngua ge  a bilit y, w or d-fi ndi ng 
diffi c ult y,  a nd c o mpr e he nsi o n  of s p o ke n  l a ngua ge .   
T he A D A S -C o g  will be a d mi nister e d t o t he s ubj ect a nd s c or e d b y a q ualifi e d, tr ai ne d 
r ater at s cr ee ni ng, bas eli ne a nd at Wee ks 4, 1 3 a nd 2 6 as i ndi cate d i n t he Sc he d ul e of 
Pr oce d ur es (Ta bl e  3). 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 1 . 
6. 1. 2  Sec o n d ar y Effi c a cy V ari a bl es  
6. 1. 2. 1  Cli ni c al De me nti a R ati n g Sc al e – S u m of B oxes 
T he Was hi ngt o n  Uni versit y  Cli n i cal De me nti a  Rati ng Scal e ( C D R) is a gl o bal 
ass ess me nt of c o gniti o n  a nd  f uncti o n   r ate d i n 6 d o mai ns: me mor y,  ori e ntati o n, j ud g me nt 
a nd pr o bl e m s ol vi ng, c o m munit y  affa irs, ho me  a nd ho b bi es, a nd pers o nal car e, w hi c h is 
us e d t o ass ess t he s e verit y of de me nti a.   
Eac h d o mai n is r ate d o n a 5 -p oi nt s cal e of f uncti o ni n g  as f oll o ws:  
•  0: 
no  i mpair me nt  
•  0. 5: 
q uesti o na bl e i mpair me nt  
•  1: 
mil d i mpair me nt  
•  2: 
mo der ate i mpair me nt  
•  3:  
s e ve r e i mpair me nt 
Pers o nal car e is s c or e d o n a 4 -p oi nt s cal e wit ho ut a 0. 5 r ati ng a vail a bl e. 
T he C D R will be a d mi nister e d t hr o ugh  s e mi -str uct ur e d i nter vi e ws t o t he s ubj ects a nd 
car e gi vers b y a q ualifi e d, tr ai ne d r ater at bas eli ne a nd Wee ks 4, 1 3 a nd 2 6 as i ndi cate d i n 
t he Sc he d ul e of Pr oce d ur es (Ta bl e  3). T he C D R -S B s c or e will  be o btai ne d b y s u m mi n g 
eac h of t he d o mai n b o x s c or es  (i.e., s u m of b o xes), wit h s c or es r a ngi ng  fr o m 0 t o 1 8. 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 2 . 
6. 1. 2. 2  Mi ni- M e nt al St at e Ex a mi n ati o n  
T he M M S E  is a bri ef c o gniti ve s cr ee ni ng meas ur e  a nd ass ess es ori e ntati o n t o ti me a nd 
pl ace, i m me di ate  a nd del a ye d r ecall of w or ds, atte nti o n  a nd cal c ul ati o n, l a ngua ge 
( na mi ng,  c o mpr e he nsi o n  a nd r e petiti o n), a nd s pati al a bilit y ( c o p yi ng  a fi gur e). T he 


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M M S E will be a d mi nister e d  t o t he s ubj ect a nd s c or e d b y a q ualifi e d, tr ai ne d r ater at 
s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3 a nd 2 6 as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es 
(Ta bl e  3). 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 3 . 
6. 1. 2. 3  Alz hei mer’s Dis e as e C o -o per ati ve St u dy Acti vit y of D ail y Li vi n g ( A D C S -A D L)  
T he A D C S -A D L  is a vali date d s cal e f or meas uri ng  f uncti o nal  a biliti es i n acti viti es of 
dail y li vi ng i n s ubj ects wit h  Al z hei mer’s dis eas e . It meas ur es 6 basi c a nd 1 7 i nstr u me ntal 
acti viti es of dail y li vi ng a nd w as s pecifi call y de vel o pe d as a s e nsiti ve t o ol t o tr ac k 
c ha nges i n f uncti o nal  perf or ma nce i n Al z hei mer’s dis eas e o ver ti me . T he basi c acti viti es 
i ncl ude s elf-car e tas ks s uc h as eati ng,  w al ki ng, t oil eti ng,  bat hi ng,  gr o o mi ng,  a nd 
dr essi ng . T he i nstr u me ntal  acti viti es ar e mor e c o mpl e x s kills t hat ar e r e q uir e d t o 
s uccessf ull y  li ve i nde pe nde ntl y  a nd i ncl ude s ho p pi ng,  kee pi ng  a p p oi nt me nts,  tr a veli ng 
o utsi de of ho me,  ma ki n g  a meal or s nac k, r ea di ng, a nd writi ng . It will be a d mi nister e d t o 
t he s ubj ect’s car e gi ver a nd s c or e d b y a q ualifi e d, tr ai ne d r ater at bas eli ne a nd Wee ks 4, 
1 3 a nd 2 6 as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es ( Ta bl e  3). 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 4 . 
6. 1. 2. 4  Ne ur o ps yc hi atri c I nve nt or y  
T he N PI is a n i nter vi e w -bas e d t o ol f or ass essi ng be ha vi or al d o mai ns c o m mo n  i n 
de me nti a  ( hall uci nati o ns,  del usi o ns, a gitati o n/ a ggr essi o n,  d ys p hori a/ de pr essi o n, a nxi et y, 
irrita bilit y, disi nhi biti o n, e up hori a, a pat hy, a berr a nt mot or be ha vi or, sl ee p a nd ni ght- ti me 
be ha vi or c ha nge,  a p petite a nd eati ng c ha nge) i n ter ms of fr e q ue nc y,  s e verit y a nd distr ess .  
T he N PI will be a d mi nister e d t o t he s ubj ect’s car e gi ver a nd s c or e d  b y a q ualifi e d, tr ai ne d 
r ater at bas eli ne a nd Wee ks 4, 1 3 a nd 2 6 as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es 
(Ta bl e  3). 
F urt her  details r e gar di ng  t he ass ess me nt ar e pr o vi de d i n A p pe ndi x 5 . 
6. 1. 2. 5  C or nell Sc al e f or De pr essi o n a n d De me nti a  
T he C -S D D w as s pecifi call y de vel o pe d t o ass ess si gns a nd s y mpt o ms  of m aj or 
de pr essi o n i n de me nte d  s ubj ects.  
T he s cal e c o ntai ns ni netee n q uesti o ns, eac h of w hi c h ca n be gi ve n a s c or e r a ngi ng  fr o m 0 
( a bs e nt) t o 2 (s e ver e) a nd is di vi de d i nt o fi ve s ub-s cal es:  
•  mo o d- r el ate d si gns: a nxi et y,  s a d ness, a mi ni mal  r eacti o n t o pl eas a nt e ve nts a nd 
irrita bilit y 
•  be ha vi or al dist ur ba nce: a gitati o n, ps yc ho mot or  r etar dati o n, multi pl e p hysi cal 
c o mpl ai nts a nd l oss of i nter est 
•  p hysi cal si gns: l oss of a p petite, w ei ght l oss a nd l ac k of e ner gy  
•  c ycli c f uncti o ns:  di ur nal vari ati o n i n mo o d, diffi c ult y falli ng asl ee p, multi pl e 
a w a ke ni ng  d uri ng  t he ni ght  a nd earl y mor ni ng  a w a ke ni ng 
•  i deati o nal dist ur ba nce: s ui ci dal te nde nci es, l o w s elf- estee m, pessi mis m a nd mo o d-
c o ngr ue nt  del usi o ns  


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T he C -S D D will be a d mi nister e d t hr o ugh  s e mi -str uct ur e d  i nter vi e ws t o t he subj ects a nd 
car e gi vers b y a q ualifi e d tr ai ne d r ater at s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3, 2 6 a nd 3 0 
as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es ( Ta bl e  3). 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 6 . 
6. 2  
S af et y V ari a ble s 
6. 2. 1  A dvers e Eve nts  
6. 2. 1. 1  C oll ecti o n of Advers e Eve nts  
It is t he r es p o nsi bilit y of t he I nvesti gat or t o c oll ect all A Es ( b ot h s eri o us a nd no n-s eri o us) 
deri ve d b y s p o nta ne o us, uns oli cite d r e p orts of s ubj ects, b y o bs er vati o n a nd b y r o uti ne 
o pe n q uesti o ni ngs  e. g., " H o w ha ve yo u  felt si nce I l ast s a w yo u ?" 
6. 2. 1. 2  Defi niti o ns  
A n A E is  any  unt o w ar d  me di cal  occ urr e nce t hat occ urs i n a s ubj ect  or cli ni cal 
i nvesti gati o n s ubj ect a d mi nister e d a p har mace uti cal  pr o d uct, a nd w hi c h d oes not 
necess aril y ha ve t o ha ve a ca us al r el ati o ns hi p wit h t his tr eat me nt. A n A E ca n t her ef or e 
be a ny  unfa v or a bl e a nd uni nte nde d  si gn (i ncl udi ng  a b nor mal  l a b or at or y fi ndi ng), 
s y mpt o m,  or dis eas e te mp or all y ass oci ate d with t he  us e of a n i nvesti gati o nal pr o d uct, 
w het her or not c o nsi der e d r el ate d t o t he pr o d uct.  
All A Es, i ncl udi ng  i nter c urr e nt  ill ness es, occ urri ng  d uri ng  t he  st ud y  will be d oc u me nte d 
i n t he e C R F. C o nc o mita nt  ill ness es, w hi c h e xiste d bef or e e ntr y  i nt o  t he  st ud y, will not be 
c o nsi der e d A Es unl ess t he y  w ors e n d uri ng  t he  tr eat me nt  peri o d . All A Es, r e gar dl ess of 
t he s o ur ce of i de ntifi cati o n ( e. g., p hysi cal e xa mi nati o n,  l a b or at or y ass ess me nt, E C G, 
r e p orte d b y s ubj ect), must   be d oc u me nte d. 
Pr e -e xisti ng c o nditi o ns will be r ec or de d i n t he  e C R F o n t he Me di cal Hist or y or  
a p pr o pri ate pa ge .  
A tr eat me nt -e mer ge nt  A E ( T E A E) will be defi ne d as a n A E t hat be gi ns or t hat w ors e ns 
i n s e verit y after at l east o ne d os e of st ud y dr ug has bee n a d mi nister e d. 
6. 2. 1. 3  Ass es s me nt of Advers e Eve nts 
Eac h A E will be ass ess e d b y t he I nvesti gat or wit h r e gar d t o t he f oll o wi ng cate gori es:  
•  Seri o us ness  
•  I nte nsit y 
•  Ca us alit y  
6. 2. 1. 3. 1  Seri o us ness  
A S A E  is defi ne d as a ny unt o w ar d me di cal occ urr e nce t hat at a ny d os e: 
•  Res ults i n deat h.  
•  Is life-t hr eate ni ng. 
T his mea ns  t hat  t he s ubj ect is at ris k of deat h at t he ti me  of t he  e ve nt;  it d oes not 
mea n t hat t he e ve nt hyp ot heti call y  mi ght  ha ve ca us e d deat h if it w er e mor e s e ver e.  
•  R e q uir es i npati e nt hos pitali zati o n or pr ol o ngat i o n  of e xisti ng hos pitali zati o n. 


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•  Res ults i n persiste nt or si gni fi ca nt dis a bilit y or i nca pacit y. 
•  Is a c o nge nital  a no mal y or birt h defect. 
•  Is a n i mp orta nt  me di cal e ve nt(s) t hat ma y not be i m me di atel y life-t hr eate ni ng  or 
r es ult i n deat h or hos pitali zati o n b ut t hat ma y  j e o par di ze t he s ubj ect or r e q uir e 
i nter ve nti o n  t o pr e ve nt o ne of t he a b o ve o utc o mes. E xa mpl es of s uc h e ve nts ar e 
i nte nsi ve tr eat me nt  i n a n e mer ge nc y  r o o m or at ho me f or all er gi c br o nc hos pas m; 
bl o o d d ys cr asi as or c o nv ulsi o ns t hat d o not r es ult i n hos pitali zati o n ;  or de vel o p me nt 
o f dr ug de pe nde nc y  or dr ug  a b us e. 
Me di cal a nd s ci e ntifi c j ud g me nt  s ho ul d be e xer cis e d i n deci di ng w het her a cas e is 
s eri o us a nd w het her e xpe dite d r e p orti ng is a p pr o pri ate. 
6. 2. 1. 3. 2  I nte nsit y 
T he i nte nsit y  of eac h A E must  be ass ess e d b y t he I nvesti gat or usi ng  o ne of t he f oll o wi ng 
cate gori es, a nd r ec or de d  i n t he  e C R F: 
•  Mil d: A n A E t hat d oes not i nterfer e wit h us ual acti viti es;  
•  M o der ate: A n A E t hat ma y  ca us e s o me i nterfer e nce wit h us ual acti viti es;  
•  Se ver e: A n A E t hat pr e ve nts us ual acti viti es  a nd is us uall y i nca pacitati ng. 
6. 2. 1. 3. 3  Ca us alit y  
T he I nvesti gat or  will ass ess t he ca us alit y/ r el ati o ns hi p bet w ee n t he st ud y  dr ug  a nd t he A E 
a nd r ec or d t hat ass ess me nt i n t he  e C R F. Ca us alit y will be s ho w n as a ‘ pr o ba bl y r el ate d’, 
‘ p ossi bl y r el ate d’, ‘ unli kel y  r el ate d’, ‘ not r el ate d’ or ‘ not ass ess a bl e’ . 
T he most li kel y ca us e of a n S A E ( e. g., dis eas e under tr eat me nt,  c o nc o mita nt  dis eas e, 
c o nc o mita nt  me di cati o n, ot her) will be i ndi cate d o n t he e C R F wit h details of t he 
c o nc o mita nt  dis eas e or me di cati o n or ot her ca us e.  
T he ca us al r el ati o ns hi p of t he A E t o st ud y dr ug will be des cri be d i n ter ms of:  
•  Pr o ba bl e: t he A E:  
- 
F oll o ws a r eas o na bl e te mp or al s e q ue nce fr o m a d mi nistr ati o n of t he st ud y dr ug.  
- 
C o ul d not be r eas o na b l y e xpl ai ne d b y t he s ubj ect’s cli ni cal state, e nvir o n me ntal 
or t o xi c fact ors or ot her t her a pi es a d mi nistr ate d t o t he s ubj ect.  
- 
Dis a p pears or decr eas es  o n cess ati o n or r e d ucti o n i n d os e of t he st ud y dr ug. 
- 
F oll o ws a kno w n  pat ter n of r es p o ns e t o t he  st ud y  dr ug. 
- 
Rea p pears or w ors e ns up o n r ec hall e nge.  
•  P ossi bl e: t he A E:  
- 
F oll o ws a r eas o na bl e te mp or al s e q ue nce fr o m a d mi nistr ati o n of t he st ud y dr ug. 
- 
C o ul d be r eas o na bl e e x pl ai ne d b y t he s ubj ect’s cli ni cal state, e nvir o n me ntal  or 
t o xi c fact ors or ot her t her a pi es a d mi nistr ate d t o t he s ubj ect. 
- 
F oll o ws a kno w n  pat ter n of r es p o ns e t o t he  st ud y  dr ug. 
•  Unli kel y:  t he A E  
- 
D oes not f oll o w a r eas o na bl e te mp or al s e q ue nce fr o m a d mi nistr ati o n  of t he st ud y 
dr ug.  


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- 
C o ul d be r eas o na bl y e xpl ai ne d b y t he s ubj ect’s cli ni cal state, e nvir o n me ntal  or 
t o xi c fact ors or ot her t her a pi es a d mi nistr ate d t o t he s ubj ect.  
- 
D oes not f oll o w a kno w n  patter n of r es p o ns e t o t he st ud y  dr ug. 
- 
D oes not r ea p pear or w ors e n up o n r ec hall e nge.  
•  N ot r el ate d:  
- 
T he A E d oes not meet t he a b o ve criteri a.  
- 
T her e is s uffi ci e nt   i nf or mati o n  t hat  t he eti ol o gy of t he  A E is not r el ate d t o t he 
stud y  dr ug.  
•  N ot ass ess a bl e / uncl assifi a bl e: 
- 
T he A E ca nnot be j ud ge d  beca us e of i ns uffi ci e nt  or c o ntr a di ct or y i nf or mati o n, 
w hi c h ca nnot be s up pl e me nte d  or verifi e d.  
T he st ud y c o nd uct  r el ate d ness f or S A Es will als o be ass ess e d a nd d oc u me nte d.  
6. 2. 1. 4  Rec or di n g Advers e Eve nts  
T he peri o d f or a d vers e e ve nt r e p orti ng will e xte nd  fr o m  si gni ng  of  i nf or me d  c o ns e nt 
until 1 4 da ys after t he l ast st ud y tr eat me nt  a d mi nistr ati o n  (i ncl udi ng  pl ace b o d uri ng  t he 
si ngl e- bli nd pl ace b o w as ho ut peri o d) . A d vers e e ve nts occ urri ng after t he e n d of t he st ud y  
s ho ul d be r e p orte d t o t he S p o ns or or S p o ns or’s desi gnee b y t he I nvesti gat or  if t he 
I nvesti gat or c o nsi ders t her e is a ca us al r el ati o ns hi p wit h t he st ud y  dr ug.  
All A Es, r e gar dl ess of t he r el ati o ns hi p t o st ud y dr ug, will be r ec or de d i n t he  e C RF. All 
A E r e p orts s ho ul d c o ntai n a bri ef des cri pti o n of t he e ve nt, date a nd ti me of o ns et, date 
a nd ti me of r es ol uti o n, i nte nsit y,  tr eat me nt  r e q uir e d, r el ati o ns hi p t o st ud y dr ug, acti o n 
ta ke n  wit h t he st ud y  dr ug, o utc o me,  a nd w het her  t he  e ve nt is cl assifi ed as s eri o us.  
6. 2. 1. 5  Re p orti n g Seri o us Advers e Eve nts  
T he I nvesti gat or  must r e p ort a ny S A Es t o t he  
Cli ni cal St udi es Safet y Ce nter 
wit hi n 2 4  ho urs  of bec o mi ng a w ar e of t he e ve nt. 
W he n  calli ng t o r e p ort a n S A E, state t hat yo u ar e r e p orti ng a n S A E a nd gi ve t he 
I nvesti gat or’s na me, yo ur na me, t he tel e p ho ne nu mber  w her e yo u ca n be r eac he d, a nd t he 
pr ot oc ol nu mber  a nd titl e. 
T he I nvesti gat or   a nd t he S p o ns or ( or S p o ns or’s desi gnee) will r e vi e w eac h S A E r e p ort 
a nd t he S p o ns or/  
will e val uate t he s eri o us ness a nd t he ca us al r el ati o ns hi p of 
t he e ve nt  t o st ud y  tr eat me nt. I n a d diti o n, t he S p o ns or ( or S p o ns or’s desi gnee) will 
e val uate t he e xpecte d ness acc or di ng t o t he r efer e nce d oc u me nt  (I nvesti gat or  Br oc hur e or 
S u m mar y  of Pr o d uct C har acteristi cs) . Bas e d o n t he I nvesti gat or a nd S p o ns or’s 
ass ess me nt of t he e ve nt, a decisi o n will be ma de c o ncer ni ng  t he nee d f or f urt her  acti o n . 
All S A Es will be r ec or de d fr o m si gni ng  of i nf or me d  c o ns e nt until  1 4 da ys after t he l ast 
st ud y  tr eat me nt  a d mi nistr ati o n  (i ncl udi ng  pl ace b o d uri ng  t he si ngl e- bli nd pl ace b o 
w as ho ut peri o d) . Seri o us A Es  occ urri ng after t he e nd of t he st ud y  a nd  c o mi ng  t o t he 
atte nti o n  of t he I nvesti gat or  must be r e p orte d o nl y if t he y ar e c o ns i der e d (i n t he o pi ni o n 
of t he I nvesti gat or) ca us all y -r el ate d t o t he i nvesti gati o nal dr ug. 




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ne o natal deat h, c o nge nital a no mal y, or birt h defect) a nd r e p orte d wit hi n 2 4  ho urs i n 
acc or da nce wit h t he pr oce d ur e f or r e p orti ng S A Es . 
6. 2. 2  L a b or at or y V ari a bl es 
La b or at or y ass ess me nts will be perf or me d b y a ce ntr al l a b or at or y, as i de ntifi e d i n t he 
List of St ud y  Pers o nnel . F or s afet y r eas o ns, l a b or at or y ass ess me nts ma y  als o  be 
perf or me d l ocall y  i n cas e of a n e mer ge nc y. 
Bl o o d s a mpl es s ho ul d  be ta ke n  usi ng  sta ndar d ve ni p unct ur e  tec hni q ues . F urt her 
i nstr ucti o ns ar e a vail a bl e i n t he Ma nual f or l a b or at or y e val uati o ns.  
T he f oll o wi ng l a b or at or y vari a bl e s will be deter mi ne d at s cr ee ni ng, bas eli ne a nd 
Wee ks  4 (li ver f uncti o n  tests o nl y), 1 3, 2 6 a nd 3 0 as i ndi cate d i n t he Sc he d ul e of 
Pr oce d ur es (Ta bl e  3): 


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T a ble  2: L a bor at or y Ass ess me nts  
He mat ol o gy:  
er yt hr oc ytes  
he mo gl o bi n  
he mat ocrit  
M C V  
M C H  
ne utr o p hils  
e osi no p hils 
bas o p hils 
l y mp hoc ytes 
mo noc ytes  
pl atel ets  
l e ukoc ytes 
E nd ocri nol o gy:  
fr ee T 4  
pr e gna nc y  test  a 
Cli ni cal 
c he mistr y:  
s o di u m 
p otassi u m  
c hl ori de 
cal ci u m 
p hos p hor us 
gl uc os e  
cr eati ni ne  
ur ea  
uri c aci d  
t otal bilir ubi n  b  
dir ect bilir ubi n  b  
indir ect bilir ubi n  b  
al kali ne p hos p hatas e  b  
A S T  b  
A L T  b  
G G T  b  
al b u mi n b  
t otal pr otei n b  
tri gl yceri des  
c hol ester ol  
cal c ul ate d cr eati ni ne cl ear a nce  
vita mi n B 1 2  
H b A 1c  
Uri nal ysis 
( macr os c o p y): 
a p pear a nce  
bilir ubi n  
c ol or 
gl uc os e  
ket o ne  
l e ukoc ytes 
nitrite  
occ ult bl o o d  
pr otei n 
r eactio n p H 
r e d uci ng  s ubsta nce 
s pecifi c gr a vit y 
Mi cr os c o p y will be d o ne if 
macr os c o p y is a b nor mal  
A L T = al a ni n e a mi n otr a nsf er ase; A S T = as p art at e a mi n otr a nsf er as e; G G T = g a m m a -gl ut a myl 
tr a ns p e pti d ase; H b A 1 c = gly c at e d h e m o gl o bi n; M C V = me a n c or p usc ul ar v ol u me; M C H = me a n c or p usc ul ar 
h e m o gl o bi n; T 4 =t h yr oxi n e . 
a.  A t s cr e e ni n g a n d We e k 2 6  f or w o me n of c hil d be ari n g p ot e nti al, a uri ne pr e g n a ncy t est will b e 
p erf or me d. P ositi ve r es ult will b e c o nfir me d b y a s er u m pr e g n a ncy t est  
b.  At We e k 4, o nl y li v er f u n cti o n t ests will b e p erf or me d.  
 
All cli ni cal l a b or at or y test r es ults o utsi de of t he r efer e nce r a nge will be i nter pr ete d b y t he 
i nvesti gat or usi ng  t he f oll o wi ng cate gori es:  
•  A b nor mal  b ut  not a cli ni call y si gnifi ca nt  w ors e ni ng  


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•  A b nor mal a nd a cli ni call y si gnifi ca nt  w ors e ni ng.  
A l a b or at or y test r es ult t hat  has si gnifi ca ntl y  w orse ne d ( acc or di ng t o me di cal j ud gme nt) 
c o mpar e d t o t he bas eli ne r es ult will be r ec or de d o n t he e C R F as a n A E.  
 
S ubj ects wit h el e vate d al a ni ne a mi notr a nsfer as e ( A L T ), as partate a mi notr a nsfer as e 
(A S T ), or t otal bilir ubi n, meeti ng  a ny o ne of  t he f oll o wi ng criteri a s ho ul d be wit hdr a w n 
fr o m t he st ud y  as des cri be d i n Secti o n 4. 3 : 
•  A L T or A S T ≥ 8 x U L N; 
•  A L T or A S T ≥ 5 x U L N  f or mor e t ha n 2 w ee ks; 
•  A L T or A S T ≥ 3 x U L N  a nd t otal bilir ubi n ≥ 2 x U L N  at t he s a me visit; 
•  A L T or A S T ≥ 3 x U L N  wit h t he a p pear a nce of s y mpt o ms  i ndi cati ng he patitis 
( e. g., w ors e ni ng fati gue,  na us ea,  v o miti ng,  ri ght  up per  q ua dr a nt pai n or te nder ness, 
fe ver, r as h, or e osi no p hili a). 
6. 2. 3  Vit al Si g ns  
T he f oll o wi ng vital si gns will be ass ess e d at s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3, 2 6 a nd 
3 0 as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es (Ta bl e  3): 
•  Bl o o d pr ess ur e (s yst oli c a nd di ast oli c; m m H g) 
S ubj ects s ho ul d be r esti ng i n a s e mi -r ec u mbe nt  p ositi o n f or at l east 1 0 mi nutes  pri or t o 
t he ass ess me nt of bl o o d pr ess ur e. T he c orr ect si ze of  t he bl o o d pr ess ur e c uff a nd t he 
c orr ect p ositi o ni ng o n t he s ubj ects’ ar m is ess e nti al t o i ncr eas e t he acc ur ac y of bl o o d 
pr ess ur e meas ur e me nts.  
6. 2. 4  El ectr oc ar di o gr a ms 
Sta ndar d 1 2 -l ea d E C Gs will be perf or me d at s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3, 2 6 a nd 
3 0 as i ndi cate d i n t he Sc he d ul e of Pr oce d ur es (Ta bl e  3). F or Wee ks 4, 1 3 a nd 2 6, E CGs 
will be perf or me d a p pr o xi matel y  3  ho urs p ost st ud y  dr ug a d mi nistr ati o n,  t he a p pr o xi mate 
ti me of ma xi mu m  c o nce ntr ati o n  of S U V N-5 0 2. 
T he E C Gs will be per f or me d acc or di ng t o t he i nstr ucti o ns i n a s e par ate E C G i nstr ucti o n 
ma nual  pr o vi de d b y t he ce ntr al E C G ve nd or  a nd r e vi e w e d b y a ce ntr al r e vi e w er .  
T he E C G par a meters (i ncl udi ng  he art r ate a nd P R, R R, Q R S, a nd Q T i nter vals) will be 
ass ess e d  b y ce ntr al r e vi e w  usi ng  a ce ntr al E C G ve nd or . 
6. 2. 5  P hysi c al a n d Ne ur ol o gi c al E x a mi n ati o ns 
P hysi cal  a nd ne ur ol o gi cal  e xa mi nati o ns ,  i ncl udi ng  w ei ght, will be perf or me d at 
s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3, 2 6 a nd 3 0 as i ndi cate d i n t he Sc he d ul e of 
Pr oce d ur es (Ta bl e  3). 
A c o mpl ete p hysi cal e xa mi nati o n  will be perf or me d b y t he  Pri nci pal I nvesti gat or . T he 
f oll o wi ng b o d y s yste ms  s ho ul d be i ncl ude d i n t he  p hysi cal e xa m: 
•  Hea d, ear, nos e, a nd t hr oat 
•  E yes  
•  Nec k  
•  Car di o vas c ul ar s yste m  


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•  Res pir at or y s yste m  
•  A b d o me n 
•  S ki n  
•  E xtr e miti es  
•  Ne ur ol o gi cal s yste m  
•  C hest  
•  M us c ul os kel etal s yste m  
E xa mi nati o n  of t he br east, r ect u m, a nd ur o ge nital s yste m  ar e at t he PI’s dis cr eti o n ( i.e., if 
cli ni call y i ndi cate d) . If a p hysi cal or ne ur ol o gi cal a b nor malit y is note d p ost-tr eat me nt, 
t he PI will i ndi cate w het her or not t he r es ult is cli ni call y si gnifi ca nt a nd if it c o nstit utes 
a n A E . 
A ge ner al ne ur ol o gi cal e xa m will be perf or me d b y t he Pri nci pal I nvesti gat or,  as 
des cri be d i n  A p pe ndi x 7 . 
6. 2. 6  A d diti o n al S af et y Ass ess m e nts  
6. 2. 6. 1  C ol u m bi a S ui ci de Severit y R ati n g Sc al e  
S ui ci dal i deati o n a nd be ha vi or will be pr os pecti vel y ass ess e d d uri ng t he st ud y usi ng t he 
C- S S R S . T he C -S S R S (s cr ee ni ng a nd si nce l ast visit versi o ns) will be a d mi nister e d b y a 
q ualifi e d tr ai ne d r ate r at s cr ee ni ng, bas eli ne a nd Wee ks 4, 1 3, 2 6 , a nd 3 0, as i ndi cate d i n 
t he Sc he d ul e of Pr oce d ur es (Ta bl e  3), as w ell as at uns c he d ul e d  visits as cli ni call y 
i ndi cate d. Site staff s ho ul d r e vi e w t he c o nte nts  of t he C -S S R S f or c o mpl ete ness a nd t he n 
tr a ns cri be t he data t o t he e C R F. 
S ubj ects w ho, at a ny ti me  d uri ng  t his st ud y,  r e p ort a n A E of s ui ci dal i deati o n or 
be ha vi or, eit her bet w ee n visits or d uri ng visit i nter vi e ws, must  be ass ess e d b y tr ai ne d 
r aters a nd r e vi e w e d b y a n M D or a cli ni c i a n P hD. S ubj ects w ho r e p ort s ui ci dal i deati o n 
wit h i nte nt, wit h or wit ho ut a pl a n or met ho d  (i.e., a p ositi ve r es p o ns e t o Ite ms 4 or 5 i n 
t he ass ess me nt of s ui ci dal i deati o n o n t he  C- S S R S) or s ui ci dal be ha vi or must  be 
e val uate d t hat da y b y a ps yc hi atrist or ot her tr ai ne d me ntal healt h pr ofessi o nal w ho is a 
li ce ns e d ps yc hol o gist,  s ocial w or ker or nurs e pr actiti o ner . O nl y  s ubj ects w hos e s ui ci dal 
i deati o n is passi ve, w ho e xpr essl y de ny a ny i nte nt  t o act, a nd w ho, after e val uati o n, ar e 
not j ud ge d t o be at s eri o us ris k f or s elf -har m d uri ng  t he c o urs e of t he st ud y  ma y  c o nti nue 
i n t he st ud y;  ot hers must  be dis c o nti nue d  fr o m  st ud y  parti ci pati o n a nd r ecei ve 
a p pr o pri ate cli ni cal f oll o w -up car e t o e ns ur e t heir s afet y.  
All r e p orts of s ui ci dal i deati o n or be ha vi or must  be r e p orte d as a n A E.  Sites s ho ul d 
i ndi cate w hi c h healt h car e pr ofessi o nals ar e t o be r es p o nsi bl e f or ac ute car e o n-site a nd 
s pecif y r eferr al ce nter(s) t o be us e d f or f urt her e val uati o n. 
F urt her details r e gar di ng t he ass ess me nt ar e pr o vi de d i n  A p pe ndi x 8 . A d diti o nal detail e d 
i nf or mati o n  c o ncer ni ng  a d mi nistr ati o n,  s c ori ng a nd r ec or di ng will als o be pr o vi de d b y 
t he Rater Tr ai ni ng  Ve nd or. 


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6. 3  
De mo gr a p hics  a n d  B as eli ne C har act e ristics 
De mo gr a p h i cs  a nd Bas eli ne C har acteristi cs c o nsist of t hos e vari a bl e s t hat ar e ass ess e d 
o nl y at s cr ee ni ng/ bas eli ne.  
6. 3. 1  S u bj ect  De m o gr a p hy 
S ubj ect  de mo gr a p hy  c o nsists of: 
•  A ge at s cr ee ni ng  
•  Hei ght  
•  Race  
•  Se x  
6. 3. 2  Dis e as e Hist or y  
F or dis eas e hist or y t he f oll o wi ng will be d oc u me nt e d: 
•  Date of first di a gnosis  
•  Date of first tr eat me nt  
•  Date of a d diti o nal tr eat me nt 
6. 3. 3  M e di c al Hist or y  
F or t he d oc u me ntati o n  of t he me di cal hist or y, a ny pr e vi o us a nd c o nc o mita nt  dis eas es 
bef or e s cr ee ni ng will be d oc u me nte d . 
T he me di cal hist or y will be o btai ne d b y i nter vi e wi ng t he s ubj ect or b y i ns pecti ng  his/ her 
me di cal r ec or ds.  
F or c o di ng of me di cal hist or y, s ee Secti o n 9. 4 . 
6. 3. 4  Pr evi o us a n d C o nc o mit a nt M e di c ati o ns 
Pr e vi o us a nd c o nc o mita nt me di cati o n will be d oc u me nte d  as des cri be d i n Secti o n  5. 7 . 
6. 4  
Ot he r Ass ess me nts  
6. 4. 1  Scr ee ni n g Ass ess m e nts  
6. 4. 1. 1  M RI a n d C T s c a n 
S ubj ects w ho di d not ha ve a n M RI  or C T s ca n wit hi n t he  past 1 2 mo nt hs  will ha ve a 
1. 5 Tesl a or 3. 0 Tesl a M RI s ca n or a C T s ca n as part of s cr ee ni ng. If a n M RI or C T s ca n 
is r e quir e d, t he s ubj ect s ho ul d be s c he d ul e d f or a Scr ee ni ng M RI o nl y after t he Pri nci pal 
I nvesti gat or or tr ai ne d desi gnee has verifi e d t hat t he s ubj ect has met all of t he i ncl usi o n 
a nd no ne of t he e xcl usi o n criteri a.  
6. 4. 1. 2  M o difi e d H ac hi ns ki Is c he mi c Sc al e ( M HI S) 
T he M HI S , a t o ol t o i de ntif y t he p ossi bilit y of a vas c ul ar eti ol o gy f or t he s ubj ect’s 
de me nti a, will be c o mpl ete d b y a q ualifi e d, tr ai ne d r ater at t he s cr ee ni ng visit, as 
des cri be d i n A p pe ndi x 9 . 


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6. 4. 1. 3  N ati o n al I nstit ut e of Ne ur ol o gi c al a n d C o m m u ni c ati ve Dis e as es a n d 
Str oke/ Alz hei mer's Dis e as e a n d Rel at e d Dis or ders Ass oci ati o n Crit eri a f or 
Pr o b a bl e Alz hei mer’s Dis e as e  
T he NI N C D S -A D R D A  criteri a f or pr o ba bl e Al z hei mer’s dis eas e will be r e vi e w e d at 
s cr ee ni ng, as des cri be d i n A p pe ndi x 1 0 . 
6. 4. 2  A p oli p o pr ot ei n E Ge n ot y pe  Testi n g  
At bas eli ne, a bl o o d s a mpl e will be dr a w n f or A P O-E ge not ype  testi ng. S ubj ect s ( or 
car e gi ver) will be pr o vi de d t he r es ults of t he test at t he c o ncl usi o n of t he st ud y,  up o n 
r e q uest. 
T o o btai n s uffi ci e nt  D N A f or A P O -E ge not ypi ng,  a si ngl e bl o o d s a mpl e of 4 m L will be 
dr a w n i nt o t he a p pr o pri ate t ube  (s ee t he La b or at or y Ma nual f or s a mpl e ac q uisiti o n, 
s hi p pi ng  a nd l a beli ng i nstr ucti o ns). 
6. 4. 3  P h ar m ac o ki neti cs 
Pl as ma s a mpl es will be a nal yze d f or l e vels of S U V N -5 0 2  a nd M 1 of  S U V N - 5 0 2 at 
stea d y state ( Wee k 4 of tr eat me nt)  a nd at Wee k 2 6 t o gat her i nf or mati o n  o n p o p ul ati o n 
p har mac o ki neti cs . Pl as ma s a mpl es will be a nal yze d f or l e vels of d o ne pezil a nd 
me ma nti ne  at s cr ee ni ng, Wee k 4 a nd at Wee k 2 6 t o deter mi ne c o mpli a nce wit h t hes e 
st ud y  tr eat me nts. 
At Wee ks 4 a nd  2 6, pl as ma s a mpl es will be c oll ecte d bef or e st ud y  dr ugs ar e 
a d mi nister e d t o t he s ubj ects. It is r ec o m me nde d,  o n t he da y pri or t o a nd/ or da y of visits 
w her e p har mac o ki neti c  ( P K ) s a mpli ng is perf or me d, t hat t he date, ti me a nd fr e q uenc y 
( q d or bi d) of S U V N- 5 0 2, d o ne pezil H Cl  a nd me ma nti ne H Cl a d mi nistr ati o n  be note d b y 
t he s ubj ect or t he car e gi ver t o deter mi ne t he ti mi ng  of l ast d os e a d mi nister e d. T his 
i nf or mati o n  will be r e vi e w e d d uri ng eac h st ud y  visit a nd e nter e d i nt o t he e C R F. 
Ve n o us bl o o d s a mpl es ( a p pr o xi matel y 6 m L)  will be c oll ecte d i n Li -He pari n vac utai ner, 
a nd ce ntrif uge d  wit hi n 3 0 mi nutes  of c oll ecti o n, f or 1 0 mi n, at 3 0 0 0 R P M at + 4° C t o 
o btai n pl as ma s a mpl es . If a r efri ger ate d ce ntrif uge  is not a vail a bl e at t he site, s a mpl es ca n 
be ce ntrif uge d  at a mbi e nt  te mper at ur e. T he bl o o d s a mpl e s ho ul d be ke pt o n cr us he d i ce 
until  ce ntrif uge d.  T he pl as ma s ho ul d be di vi de d i nt o 4 t ubes: 
•  O ne t ube will be us e d f or pl as ma l e vels of S U V N -5 0 2  a nd M 1 of S U V N - 5 0 2. 
•  O ne t ube will be us e d f or pl as m a l e vels of d o ne pezil a nd me ma nti ne .   
•  T he r e mai ni ng t w o t ubes will s er ve as bac k up  s a mpl es a nd s ho ul d  be s hi p pe d 
s e par atel y fr o m t he pri mar y s a mpl es. 
At s cr ee ni ng, o nl y 2 t ubes ar e r e q uir e d f or pl as ma l e vels of d o ne pezil a nd me ma nti ne 
( 1 pri mar y s a mpl e a nd 1 bac kup  s a mpl e). 
All P K s a mpl es s ho ul d be st or e d at - 7 0° C. 
O n t he da y of s a mpl e c oll ecti o n, t he pri mar y s a mpl es s ho ul d be s hi p pe d o n dr y i ce t o t he 
bi oa nal yti cal l a b.  
If t he st ud y  ce nter has a - 7 0°C fr eezer, bac kup s a mpl es s ho ul d be st or e d at -7 0° C a nd 
s hi p pe d mo nt hl y o n  dr y i ce t o t he bi oa nal yti cal l a b. If t he st ud y  ce nter d oes not ha ve 
a - 7 0°C fr eezer , bac kup  s a mpl es s ho ul d be st or e d at - 2 0° C a nd s hi p pe d o n dr y i ce t o t he 
bi oa nal yti cal l a b , o ne da y after t he s a mpl e c oll ecti o n. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
4 8  of 1 4 3  
0 2 Mar c h 2 0 1 6  
7  
S T U D Y  C O N D U C T  
7. 1  
Sc he d ule   of Pr oce d ure s  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
4 9  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T a ble  3: Sc he d ule   of Pr oce d ure s  
St u d y  pe ri o d  
Sc re e ni n g  
B as e li ne  
Tre at me nt Pe ri o d  
E n d of  Tre at me nt  
F oll o w -u p  
Ti me  
 
D a ys  -2 8 t o -1 4 a 
 
D a y  1 a 
We e k 4  
D a y 2 8 ± 2  
We e k 1 3  
D a y  9 1 ± 2  
We e k 2 6  
D a y  1 8 2 ± 3   
o r  e arl y wit h dr a wal 
We e k 3 0  
D a y  2 1 0 ± 2  
Vis it n u m be r  
1  
2  
3  
4  
5  
6  
Pr o c e d ure s  
 
 
 
 
 
 
I nf or me d  Co ns e nt  
X  
 
 
 
 
 
I nclusio n / E xclusio n Criteria  
X  
X  
 
 
 
 
D e m o gra p hics,  Me dic al  Hist or y  
X  
X  
 
 
 
 
Prior  a n d C o nc o mita nt  Me dic atio ns  
X 
X 
X 
X 
X 
X 
M RI or C T Sc a n (if N e c ess ar y)  
X  
 
 
 
 
 
Blo o d  Sa m ple  f or A P O -E Ge n ot y pe  T e stin g 
 
X  
 
 
 
 
St u d y  Tre at me nt D is pe ns atio n b  
 
X  
X 
X 
X  
 
M M S E  a n d A D A S -C o g  
X  
X  
X  
X  
X  
 
M o difie d  H a c hins ki  Is c he mic  Sc ale  
X  
 
 
 
 
 
C D R -S B, A D C S -A D L, a n d N PI  
 
X  
X  
X  
X  
 
C -S D D  
X  
X  
X  
X  
X  
X  
C -S S R S  
X  
X  
X  
X  
X  
X  
Re vie w  of A Es  
X  
X  
X  
X  
X  
X  
La b orat or y  Tests  
X c 
X  
X d  
X  
X c 
X  
Blo o d  Press ure Me as ure me nts  
X  
X  
X  
X  
X  
X  
E C G  
X  
X  
X e 
X e 
X e 
X  
P h ysic al  a n d N e ur olo gic al  E xa minatio n  
X  
X  
X  
X  
X  
X  
Plas ma L e vels of S U V N -5 0 2  a n d M 1  of S U V N -5 0 2  
 
 
X  f 
 
X  f 
 
Plas ma Le vels  of D o ne pe zil  a n d  M e ma ntine  
X 
 
X  f 
 
X  f 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
5 0  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T a ble  3: Sc he d ule   of Pr oce d ure s ( C o nti n ue d) 
A D A S -C o g = Alz h ei mer’s Dis e ase Ass ess me nt  S c al e; A D C S -A D L = Alz hei mer’s Dis e as e C o o per ati ve  St u dy Acti vit y of D ail y Li vi n g; A E = a d v erse e ve nt; 
A P O - E= A p oli p o pr ot ei n E ; C D R -S B = Cli ni c al De me nti a R ati n g S c al e – S u m of B o x es ; C-S D D = C or nell S c al e of De pressi o n a n d De me nti a ; C-S S R S = C ol u m bi a 
S ui ci d e S e verity R ati n g S c ale ; C T = C o m p ut e d T o m o gr a p hy; E C G = El e ctr oc ar di o gr a m; M HI S = M o difi e d H a c hi ns ki Is c h e mi c S c al e; M M S E = Mi ni -Me nt al St ate 
Ev al u ati o n ; M RI = M a g n etic Res o n a nce I m a gi n g; N PI = Ne ur o ps yc hi atri c I n v e nt or y . 
 
N ot e:  It is str o n gl y r e c o m me n de d t h at o n e rat er is assi g n e d f or e a c h s u bj ect f or e a c h of t h e f oll o wi n g assess me nt s c al es s o t h at o n e r ater s c or es a s u bje ct’s 
ass ess me nt f or t h e e ntir e st u dy: M M S E, A D A S -C o g , C D R-S B, A D C S -A D L, N PI, C -S D D, a n d C -S S R S.  
 
a.  F or S cr e e ni n g a n d B as eli ne Visits, t h e f oll o wi n g ass ess me nts , i n cl u de d i n st u dy e ntry crit eri a, s h o ul d b e p erf or me d first i n or d er t o li mit t h e n u m ber of 
ass ess me nts p erf or me d f or  s u bj ects w h o d o n ot me et t he st u dy e ntry crit eri a: M M S E, t h e M HI S , C-S D D, C -S S R S, E C G, pr e g n a n cy t est (f or w o me n of 
c hil d b e ari n g p ot e nti al), a n d l a b or at or y t ests. 
b.  O n t h e d a y of t h e st u d y visits, s u bj ects will b e i nstr u ct e d n ot t o t a ke t h eir tr e at me nt at h o me, as tr e at me nt will b e dis pe nse d at t h e st u dy ce nt er . 
c.  A uri n e pr e g n a ncy t est wi ll b e d o n e at s cr e e ni n g a n d We e k 2 6 visit f or w o me n of c hil d be ari n g p ot e nti al. A p ositi ve uri ne t est will b e c o nfir me d b y a 
s er u m pr e g n a ncy t est. 
d.  At We e k 4, l a b or at or y t ests will o nl y i n cl u d e li v er f u ncti o n t ests . 
e. 3 h o urs aft er st u dy tr e at me nt a d mi nistr ati o n, i .e. t h e a p pr oxi m at e ti me of m a xi m u m c o n ce ntr ati o n of S U V N-5 0 2 . 
f. 
Pl as m a s a m pl es f or P K ass ess me nts will b e c oll ect e d b ef ore st u d y dr u gs ar e a d mi nist er e d t o t h e s u bje cts.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
5 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
7. 2  
Pr oce d ure s by Visit  
Visits s ho ul d occ ur wit hi n ± 2 da ys ( e xce pt w her e note d) of t he s c he d ul e d visit. All ti mes 
s ho ul d be r ec or de d usi ng t he 2 4-ho ur cl oc k ( e. g., 2 3: 2 0, not 1 1: 2 0  p m).   
F or Scr ee ni ng  a nd Bas eli ne Visits, t he f oll o wi ng ass ess me nts,  i ncl ude d i n st ud y  e ntr y 
criteri a, s ho ul d be perf or me d first i n or der t o  li mit t he nu mber  of ass ess me nts perf or me d 
f or s ubj ects w ho d o not meet the st ud y  e ntr y  criteri a: M M S E,  M HI S , C-S D D, C -S S R S, 
E C G, pr e gna nc y  test (f or w o me n of c hil d beari ng p ote nti al), a nd l a b or at or y tests.  It is 
str o ngl y  r ec o m me nde d  t hat o ne r ater is assi gne d f or eac h s ubj ect f or eac h of t he 
f oll o wi ng ass ess me nt s cal es s o t hat o ne r ater s c or es a s ubj ect’s ass ess me nt f or t he e ntir e 
st ud y:  M M S E,  A D A S-C o g ,  C D R-S B, A D C S -A D L,  N PI,  C -S D D, a nd C -S S R S.  
7. 2. 1  Scr ee ni n g ( Visit 1 , D ay - 2 8 t o - 1 4) 
T he s cr ee ni ng visit ( visit 1) will ta ke pl ace 1 4 t o 2 8 da ys bef or e t he bas eli ne visit . T he 
f oll o wi ng pr oce d ur es will be perf or me d: 
•  O btai n writte n i nf or me d  c o ns e nt;  
•  I ncl usi o n/ e xcl usi o n  criteri a r e vi e w i ncl udi ng 
- 
De mo gr a p hi cs  
- 
NI N C D S -A D R D A  criteri a  
- 
M M S E  
- 
C- S D D  
- 
M HI S  
- 
M RI  or C T s ca n if not pe rf or me d wit h t he past 1 2 mo nt hs 
- 
Me di cal hist or y  
- 
Pri or a nd c o nc o mita n t  tr eat me nt r e vi e w 
- 
C- S S R S  (s cr ee ni ng versi on)  
•  A E r e vi e w  
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e meas ur e me nt  
•  E C G  
•  Bl o o d a nd uri ne s a mpl es f or cli ni cal l a b or at or y tests , i ncl udi ng  pr e gna nc y  test f or 
w o me n of c hil d beari ng p ote nti al 
•  Pl as ma s a mpl e f or meas ur e me nt  of d o ne pezil a nd me ma nti ne  l e vels.  
•  A D A S -C o g  
7. 2. 2  B as eli ne Visit  ( Visit 2, D ay 1) 
T he f oll o wi ng pr oce d ur es will be perf or me d at t he bas eli ne visit o n Da y 1 of t he st ud y: 
•  I ncl usi o n/ e xcl usi o n  criteri a r e vi e w 
•  Me di cal hist or y  
•  A E  r e vi e w 
•  C o nc o mita nt  me di cati o ns r e vi e w 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
5 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e meas ur e me nt  
•  M M S E  
•  A D A S -C o g  
•  C D R -S B, A D C S -A D L,  N PI a nd C -S D D  
•  C- S S R S (si nce l ast visit versi o n) 
•  E C G  
•  Bl o o d a nd uri ne s a mpl es f or cli ni cal l a b or at or y tests  
•  Bl o o d s a mpl e f or A P O- E ge not ype  testi ng 
•  St ud y dr ug dis pe ns ati o n  
7. 2. 3  W ee k 4  Visit ( Visit 3, D ay 2 8) 
T he f oll o wi ng pr oce d ur es will be perf or me d at Wee k 4 ( Da y 2 8 ± 2 da ys) of t he st ud y:  
•  A E  r e vi e w 
•  C o nc o mita nt  me di cati o ns r e vi e w  
•  Pl as ma s a mpl e f or meas ur e me nt  of S U V N - 5 0 2,  M 1 of S U V N-5 0 2,  d o ne pezil a nd 
me ma nti ne  l e vels 
•  Bl o o d s a mpl e f or li ver f uncti o n  tests 
•  St ud y  dr ug c o mpli a nce c hec k a nd dis pe ns ati o n  
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e meas ur e me nt  
•  M M S E  
•  A D A S -C o g  
•  C D R -S B, A D C S -A D L,  N PI a nd C -S D D  
•  C- S S R S  (si nce l ast visit versi o n) 
•  E C G 3 ho urs p ost -treat me nt 
7. 2. 4  W ee k 1 3 Visit ( Visit 4, D ay 9 1) 
T he f oll o wi ng pr oce d ur es will be perf or me d at Wee k 1 3 ( Da y 9 1 ± 2 da ys) of t he st ud y:  
•  A E  r e vi e w 
•  C o nc o mita nt  me di cati o ns r e vi e w  
•  St ud y  dr ug c o mpli a nce c hec k a nd dis pe ns ati o n  
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e  meas ur e me nt  
•  Bl o o d a nd uri ne s a mpl es f or cli ni cal l a b or at or y tests  
•  M M S E  
•  A D A S -C o g  
•  C D R -S B, A D C S -A D L,  N PI a nd C -S D D  
•  C- S S R S  (si nce l ast visit versi o n) 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
5 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
•  E C G 3 ho urs p ost- tr eat me nt 
7. 2. 5  W ee k 2 6 Visit ( Visit 5, D ay 1 8 2) 
T he f oll o wi ng pr oce d ur es will be perf or me d at Wee k 2 6 ( Da y 1 8 2± 3 da ys) of t he st ud y:  
•  A E  r e vi e w 
•  C o nc o mita nt  me di cati o ns r e vi e w  
•  Pl as ma s a mpl e f or meas ur e me nt  of S U V N - 5 0 2,  M 1 of S U V N-5 0 2,  d o ne pezil a nd 
me ma nti ne  l e vels  
•  St ud y  dr ug c o mpli a nce c hec k  a nd dis pe ns a ti o n 
•  Bl o o d a nd uri ne s a mpl es f or cli ni cal l a b or at or y tests, i ncl udi ng  pr e gna nc y  test f or 
w o me n of c hil d beari ng p ote nti al 
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e meas ur e me nt  
•  M M S E  
•  A D A S -C o g  
•  C D R -S B, A D C S -A D L,  N PI a nd C -S D D  
•  C- S S R S  (si nce l ast visit versi o n) 
•  E C G 3 ho urs p ost- tr eat me nt 
7. 2. 6  W ee k 3 0 Visit ( Visit 6, D ay 2 1 0) 
T he f oll o wi ng pr oce d ur es will be perf or me d at Wee k 3 0 ( Da y 2 1 0 ± 2 da ys) of t he st ud y:  
•  A E  r e vi e w 
•  C o nc o mita nt  me di cati o ns r e vi e w  
•  P hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  
•  Bl o o d pr ess ur e meas ur e me nt  
•  Bl o o d a nd uri ne s a mpl es f or cli ni cal l a b or at or y tests  
•  C- S D D  
•  C- S S R S  (si nce l ast visit versi o n) 
•  St ud y  dr ug c o mpli a nce c hec k 
•  E C G  
7. 2. 7  E arl y Ter mi n ati o n a n d F oll o w- U p Visit s 
S ubj ect s w ho dis c o nti nue earl y fr o m t he st ud y s ho ul d, if p ossi bl e, ha ve a n Earl y 
Ter mi nati o n  visit . T his visit s ho ul d ta ke pl ace as s o o n as p ossi bl e after t he s ubj ect  st o ps 
ta ki ng  st ud y  dr ug.  T he o bs er vati o ns a nd pr oce d ur es s c he d ul e d f or Visit 5 ( Wee k 2 6) 
s ho ul d be perf or me d at t he Earl y Ter mi nati o n visit. If t he s ubj ect a gr ees, he/s he  s ho ul d 
r et ur n f or a f oll o w- up visit 4 w ee ks l ater . T he o bs er vati o ns a nd pr oce d ur es s c he d ul e d f or 
Visit  6 s ho ul d be perf or me d at t he F oll o w -up visit .  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
5 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
8  
S T A TI S TI C A L  M E T H O D S  
T he statisti cal c o nsi der ati o ns s u m mari ze d  i n t his s ecti o n o utli ne t he pl a n f or data a nal ysis 
of t his st ud y .  
Bef or e unbli ndi ng,  a s e par ate statisti cal a nal ysis pl a n ( S A P) will be fi nali ze d, pr o vi di ng 
detail e d met ho ds  f or t he a nal ys es o utli ne d bel o w .  
A ny de vi ati o ns fr o m t he pl a nne d a nal ys es will be des cri be d a nd j ustifi e d i n t he fi na l 
i nte gr ate d cli ni cal st ud y r e p ort. 
8. 1  
St u dy  S u bj e ct s 
8. 1. 1  Dis p ositi o n of S u bj ect s 
T he nu mber  a nd per ce nta ge of s ubj ects e nteri ng  a nd c o mpl eti ng  eac h p has e of t he  st ud y 
will be pr e s e nte d, str atifi e d b y tr eat me nt. 
A s ubj ect  w ho c o mpl etes all visits up t o Wee k 3 0, will be c o nsi der ed t o ha ve c o mpl ete d 
t he st ud y. F or e val uati o n of effi cac y, a c o mpl ete d s ubj ect is defi ne d as a ny s ubj ect w ho 
c o mpl etes all visits up t o Wee k 2 6.  
T he dis p ositi o n of s ubj ects will als o i ncl ude i nf or mati o n  o n t he  nu mber  a nd per ce nta ge 
of s ubj ects w ho: 
•  C o m pl ete d st ud y dr ug a nd f oll o w -up.  
•  C o mpl ete d st ud y dr ug b ut not f oll o w -up.  
•  W it hdr e w fr o m  st ud y dr ug b ut c o mpl ete d f oll o w -up.  
•  W it hdr e w fr om st ud y dr ug a nd fr o m f oll o w -up.  
8. 1. 2  Pr ot oc ol Devi ati o ns  
De vi ati o ns fr o m t he pr ot oc ol i ncl udi ng vi ol ati o ns of i ncl usi o n/ e xcl usi o n criteri a will be 
ass ess e d as “ mi nor ” or “ maj or ” i n c o o per ati o n wit h t he S p o ns or . Maj or de vi ati o ns fr o m 
t he pr ot oc ol will l ea d t o t he e xcl usi o n of a s ubj ect fr o m  t he E val ua bl e P o p ul ati o n ( E P). 
De vi a ti o ns will be defi ne d pri or t o unbli ndi ng. 
8. 1. 3  A n al ysis Sets  
M o difi e d i nte nt  t o tr eat (I T T) p o p ul ati o n: 
All r a nd o mi ze d s ubj ects w ho r ecei ve at l east 
o ne d os e of st ud y me di cati o n a nd ha ve o ne 
p ost- bas eli ne e val uati o n of t he pri mar y 
effi cac y vari a bl e.  
E val ua bl e P o p ul ati o n ( E P):  
All r a nd o mi ze d s ubj ects w ho c o mpl ete 
2 6 w ee ks of tr eat me nt,  ar e c o mpli a nt  wit h 
ta ki ng  st ud y  me di cati o n  ( ≥8 0 %), a nd ha ve 
no si gnifi ca nt pr ot oc ol de vi ati o ns. 
Safet y  P o p ul ati o n  ( S P) : 
All r a nd o mi ze d s ubj ects w ho r ecei ve at l east 
o ne d os e of st ud y  me di cati o n. 
Effi cac y a nal ys es will be perf or me d o n t he mo difi e d I T T p o p ul ati on a nd t he E val ua bl e 
E P . T he pri mar y effi cac y a nal ysis will be bas e d o n t he mo difi e d I T T p o p ul ati o n a nd a 
s ec o ndar y a nal ysis will als o be perf or me d bas e d up o n t he E P, t o ass ess t he s e nsiti vit y of 


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t he a nal ysis t o t he c hoi ce of a nal ysis s et. All ot her s ec o ndar y effi cac y a nal ys es will als o 
be perf or me d o n t he mo difi e d I T T p o p ul ati o n a nd t he E P. 
Safet y a nal ys es will be perf or me d o n t he S P . Pati e nts will be assi gne d t o t he tr eat me n t 
gr o up bas e d o n t he act ual tr eat me nt  r ecei ve d.  
De mo gr a p hi c  a nd bas eli ne c har acteristi cs will be e val uate d f or t he mo difi e d I T T 
p o p ul ati o n. If o ne or mor e s ubj ects r ecei ve d i nc orr ect st ud y dr ug,  t hes e s u m mari es will 
als o be pr es e nte d f or t he s afet y s et.  
8. 2  
G e ne r al C o nsi de r ati o ns  
All statisti cal tests will be t w o -si de d a nd will be perf or me d at t he 5 % l e vel of 
si gnifi ca nce, unl ess ot her wis e state d. 
C o nti nuo us  data will be s u m mari ze d  b y tr eat me nt  gr o up usi ng  des cri pti ve statisti cs 
( nu mber,  mea n, me di a n, sta ndar d de vi ati o n [ S D], mi ni mu m,  a nd ma xi mu m). Cate gori cal 
data will be s u m mari ze d  b y tr eat me nt  gr o up usi ng fr e q ue nc y  ta bl es (fr e q ue nci es a nd 
per ce nt).  
A nal ysis a n d dat a c o nve nti o ns:  
Defi niti o n of bas eli ne  
T he bas eli ne ass ess me nt will be t he l atest, vali d pr e - d os e ass ess me nt a vail a bl e.  
Uns c he d ul e d  ass ess me nts  
E xtr a ass ess me nts (l a b or at or y data or vital si gns ass oci ate d wit h no n -pr ot oc ol cli ni cal 
visits or o btai ne d  i n t he  c o urs e of i nvesti gati ng  or ma na gi ng A Es ) will be i ncl ude d i n 
listi ngs, b ut not  s u m mari es. If  mor e t ha n o ne l a b or at or y val ue is a vail a bl e f or a gi ve n 
visit, t he first vali d o bs er vati o n will be us e d i n s u m mari es  a nd all o bs er vati o ns will be 
pr es e nte d i n listi ngs . It is note d t hat i nvali d l a b or at or y data ma y  not be us e d (fr o m 
he mol yze d  s a mpl es, mis ha nd l e d s a mpl es, q ua ntit y  not s uffi ci e nt, or ot her c o nditi o ns t hat 
w o ul d r e nder val ues i nvali d).  
Missi ng data c o nve nti o ns  
I n ge ner al, data will not be i mp ute d,  unl ess state d ot her wis e . I mp utati o n details will be i n 
t he S A P. 
P o oli ng 
P o ol e d sites will  be us e d i n t he effi cac y a nal ys e s. Sites wit h fe w er t ha n 5 s ubj ects  i n a ny 
tr eat me nt  gr o up will be p o ol e d t o get her. Starti ng wit h t he s mall est site, p o oli ng will be 
carri e d o ut wit h t he ne xt s mall est site until t he criteri a f or at l east 5 s ubj ects per tr ea t me nt 
gr o up ha ve bee n met . If t he p o ol e d site is l ar ger t ha n 1. 5 x t he l ar gest site, p o oli ng will be 
mo difi e d t o cr eate mor e t ha n o ne p o ol e d site . Details of t he p o oli ng will be d oc u me nte d 
pri or t o br ea ki ng t he bli nd.  
O utli er s 
A ny o utli ers t hat ar e detecte d  d uri ng  t he bli nd r e vi e w of t he data will be i nvesti gate d . If 
necess ar y, q ueri es will be iss ue d t o t he I nvesti gat or,  t o eit her c orr ect or c o nfir m  t he 
o utli er.  


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De mo gr a p hics, Me dic al  Hist or y, B as eli ne C har act e ristics , a n d  C o nc o mit a nt 
Me dic ati o ns  
De mo gr a p hi c  data, me di cal hist or y, c o nc o mita nt  dis eas e , a nd c o nc o mita nt  me di cati o n 
will be s u m mari ze d usi ng  des cri pti ve statisti cs, o ver all a nd str atifi e d b y tr eat me nt. 
8. 4  
Tre at me nt  C o m pli a nce  
Tr eat me nt  C o mpli a nce is cal c ul ate d as:  
N u m ber of c o m pli a nt da ys  
× 1 0 0 %  
E x pe ct e d n u m ber of c o m pli a nt da ys  
N u mber  of c o mpli a nt da ys is t he nu mber  of da ys o n w hi c h d o ubl e -bli nd tr eat me nt  w as 
ta ke n. 
E xpecte d nu mber  of c o mpli a nt da ys is t he nu mber  of da ys t hat d o ubl e- bli nd tr eat me nt  is 
s c he d ul e d bas e d o n t he s ubj ect’s d ur ati o n of parti ci pati o n i n  t he st ud y,  e xcl udi ng  t he 
f oll o w-up p has e . 
Tr eat me nt  c o mpli a nce will be s u m mari ze d usi ng  des cri pti ve statisti cs, str atifi e d b y 
tr eat me nt. 
8. 5  
Effic ac y A nal ys es 
8. 5. 1  Pri m ar y Effi c acy A n al ysis  
8. 5. 1. 1  Hy p ot hes e s t o be Test e d 
T he pri mar y hyp ot hes es  will c o m par e eac h d os e of S U V N -5 0 2  wit h pl ace b o . T he null 
a nd alter nati ve hyp ot hes es  t o be teste d ar e as f oll o ws:  
 
𝐻𝐻𝐻𝐻: 𝜇𝜇̂ 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆−5 0 2  5 0  𝑚𝑚𝑚𝑚=  𝜇𝜇̂ 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 
𝐻𝐻𝐻𝐻: 𝜇𝜇̂ 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆−5 0 2  5 0  𝑚𝑚𝑚𝑚≠ 𝜇𝜇̂ 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 
a nd 
𝐻𝐻𝐻𝐻: 𝜇𝜇̂ 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆−5 0 2  1 0 0  𝑚𝑚𝑚𝑚=  𝜇𝜇̂ 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 
𝐻𝐻𝐻𝐻: 𝜇𝜇̂ 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆−5 0 2  1 0 0  𝑚𝑚𝑚𝑚≠ 𝜇𝜇̂ 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 
 
w her e 𝜇𝜇̂  is t he mea n c ha nge fr o m bas eli ne at w ee k 2 6 f or t he A D A S- C o g  s c or e. 
8. 5. 1. 2  St atisti c al M et h o ds  
C h a nge  fr o m bas eli ne i n A D A S -C o g  s c or e will be a nal yze d usi ng a mi xe d effects mo del 
f or r e peate d meas ur es ( M M R M) bas e d o n mI T T  p o p ul ati o n. T he mo del will i ncl ude 
fi xe d cate gori cal fact ors f or tr eat me nt,  p o ol e d site, w ee k, a nd tr eat me nt- b y-w ee k 
i nter acti o n, as w ell as a c o nti nuo us  c o vari ate of bas eli ne s c or e a nd t he bas eli ne s c or e- b y-
w ee k i nter acti o n . A n unstr uct ur e d  c o vari a nce matri x will be us e d t o mo del t he vari ati o n 
wit hi n s ubj ect f or t he r e peate d meas ur es . Missi ng data will be mai ntai ne d  as missi ng . 
T he Least S q uar e ( L S ) mea ns of eac h  tr eat me nt  gr o up, a nd t he differ e nces bet w ee n eac h 


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S U V N - 5 0 2  d os e gr o up ( 5 0 mg  a nd 1 0 0 mg)  a nd pl ace b o will be r e p orte d f or Wee ks 4, 
1 3 a nd 2 6, al o ng wit h t he c orr es p o ndi ng 9 5 % c o nfi de nce i nter vals  a nd p-val ues.  
Se nsiti vit y a nal ys es t o ass ess t he i mpact of missi ng data will be c o nd ucte d . T hes e 
a nal ys es will utili ze t he s a me met ho ds  as des cri be d pr e vi o usl y. O ne a nal ysis will us e t he 
E P a nal ysis  s et a nd a not her  will us e t he  mI T T  p o p ul ati o n b ut  will i mp ute  missi ng  data 
usi ng  L O C F . If w arr a nte d, a d diti o nal a nal ys es ma y  be i nvesti gate d.  
8. 5. 1. 3  S u b gr o u p An al ys es 
E xpl or at or y s ub gr o up  a nal ys es will be d o ne acc or di ng t o t he A P O -E 4 carri er stat us . T he 
s a me M M R M  mo del will be us e d wit h t he a d diti o n of t he f oll o wi ng fi xe d cate gori cal 
fact ors; A P O-E 4 carri er stat us a nd tr eat me n t- b y-A P O -E 4  carri er stat us i nter acti o n.  
8. 5. 2  Sec o n d ar y Effi c acy A n al ys es  
C ha nge  fr o m bas eli ne i n t he s ec o ndar y vari a bl es will be a nal yze d a nd r e p orte d i n a 
si mil ar ma nner as t he pri mar y effi cac y vari a bl e, w hi c h will i ncl ude:  
•  C D R -S B  
•  M M S E  
•  A D C S -A D L  
•  N PI  
•  C- S D D  
8. 6  
S af et y A nal ys es  
8. 6. 1  A dvers e Eve nts  
A d vers e e ve nts will be c o de d usi ng  Me di cal Di cti o nar y f or Re gul at or y  Acti viti es 
( Me d D R A). 
T he nu mber  a nd per ce nta ge of s ubj ects r e p orti ng T E A Es, tr eat me nt  e mer ge nt  S A Es 
i ncl udi ng  deat hs, T E A Es c o nsi der e d r el ate d t o st ud y dr ug a nd T E A Es l ea di ng t o 
dis c o nti nuati o n  fr o m  st ud y  dr ug  will be ta b ul ate d b y tr eat me nt,  S yste m  Or ga n  Cl ass 
( S O C) a nd pr eferr e d ter m ( P T). 
T he T E A Es  b y  ma xi mu m  s e verit y a nd r el ati o ns hi p will als o be ta b ul ate d b y tr eat me nt, 
S O C a nd P T . 
A b y -s ubj ect A E  data lis ti ng (i ncl udi ng  T E A Es) will be pr o vi de d .  
8. 6. 2  L a b or at or y Ass ess m e nts  
Des cri pti ve statisti cs b y tr eat me nt  will be pr o vi de d f or t he o bs er ve d val ues a nd c ha nges 
fr o m bas eli ne at eac h s c he d ul e d visit wit h l a b or at or y ass ess me nt. 
A s hift ta bl e ( a b nor mal l o w, nor mal, a b nor mal hi gh) will be pr o vi de d f or s el ecte d 
l a b or at or y tests. 
A b y -s ubj ect l a b or at or y ass ess me nts data listi ng will be pr o vi de d. 


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8. 6. 3  Vit al Si g ns  
Des cri pti ve statisti cs b y tr eat me nt  will be pr o vi de d f or t he o bs er ve d val ues a nd c ha nges 
fr o m bas eli ne at eac h s che d ul e d visit wit h vital si gns ass ess me nt.  
A b y -s ubj ect vital si gns data listi ng will be pr o vi de d. 
8. 6. 4  El ectr oc ar di o gr a ms 
A b y -s ubj ect data listi ng of E C G par a meters a nd fi ndi ngs  will be pr o vi de d. 
El ectr oc ar di o gr a m par a meters will be s um mari ze d  b y visit usi ng a p pr o pri ate des cri pti ve 
statisti cs. 
8. 6. 5  P hysi c al a n d Ne ur ol o gi c al E x a mi n ati o ns 
A b y -s ubj ect p hysi cal a nd ne ur ol o gi cal e xa mi nati o ns  data listi ng will be pr o vi de d.  
Res ults of t he p hysi cal a nd ne ur ol o gi cal e xa ms  will be s u m mari ze d  b y visit usi ng 
a p pr o pri ate des cr i pti ve statisti cs. 
8. 6. 6  A d diti o n al S af et y Ass ess m e nts  
A b y -s ubj ect C- S S R S data listi ng will be pr o vi de d. 
C ha nge  fr o m  bas eli ne i n C- S S R S s c or es will be s u m mari ze d  b y visit a nd differ e nces 
bet w ee n eac h S U V N - 5 0 2  d os e gr o up ( 5 0 mg  a nd 1 0 0 mg) a nd pl ace b o will be r e p orte d 
f or Wee ks 4, 1 3 a nd 2 6. 
8. 7  
P har mac o ki netics  A nal ys es  
C o nce ntr ati o n  data will be s u m mari ze d  f or S U V N -5 0 2  a nd M 1  of  S U V N - 5 0 2 f or eac h 
tr eat me nt  gr o up, b y visit, usi ng des cri pti ve statisti cs.  
C o nce ntr ati o n  data f or d o ne pezil a nd me ma nti ne  will be s u m mari ze d  f or eac h tr eat me nt 
gr o up, b y visit, usi ng des cri pti ve statisti cs . T hes e s u m mari es will be bas e d o n t he S P . 
8. 8  
I nt e ri m  A nal ys e s 
N o i nteri m  a nal ysis is pl a nne d f or t his st ud y . 
8. 9  
Det e r mi nati o n  of S a m ple  Siz e  
A t otal of 5 3 7 s ubj ects will be r a nd o mi ze d i nt o o ne of t hr ee tr eat me nt  gr o ups,  S U V N-
5 0 2 ( 5 0 mg), S U V N- 5 0 2  ( 1 0 0 mg) or pl ace b o ( 1 7 9 s ubj ects per gr o up ). Wit h a s a mpl e 
si ze of 5 3 7 s ubj ects, t her e is at l east 8 0 % p o w er t o detect a 2-p oi nt dr ug - pl ace b o 
differ e nce o n t he A D A S- C o g   wit h a sta ndar d de vi ati o n of 6, ass u mi ng  a t w o-si de d 5 % 
si gnifi ca nce l e vel a nd a dr o p-o ut r ate of 2 0 %  or l ess. 




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T he s pecifi c pr oce d ur es t o be us e d f or data e ntr y a nd q uer y r es ol uti o n usi ng t he e C R F 
will be pr o vi de d t o st ud y  sites i n a tr ai ni ng  ma nual  a nd e C R F e ntr y  gui deli nes . I n 
a d diti o n, site pers o nnel will r ecei ve tr ai ni ng o n t he e C R F. 
9. 2. 1  D at a C oll ecti o n   
T he Investi gat ors ( a nd a p pr o pri atel y a ut hori ze d  staff) will be gi ve n access t o a n o nli ne 
w e b - bas e d E D C) s yste m  w hi c h is 2 1 C F R Part 1 1 c o mpli a nt. T his s yste m is s pecifi call y 
desi gne d f or t he c oll ecti o n of t he cli ni cal data i n el ectr o ni c f or mat . Access a nd ri ght t o 
t he E D C s yste m  will be car ef ull y c o ntr oll e d a nd c o nfi gur e d acc or di ng t o eac h 
i ndi vi d ual’s r ol e t hr o ugho ut  t he  st ud y. I n  ge ner al, o nl y t he  i nvesti gat or a nd a ut hori ze d 
staff will be a bl e t o e nter data a nd ma ke  c orr ecti o ns i n t he e C R Fs. 
T he e C R F s ho ul d be c o mpl ete d f or eac h s ubj ect i ncl ude d i n t he  st ud y  a nd s ho ul d r efl ect 
t he l atest o bs er vati o ns o n t he s ubj ects parti ci pati ng  i n t he st ud y. T her ef or e, t he e C R Fs 
ar e t o be c o mpl ete d as s o o n as p ossi bl e d uri ng or i m me di atel y after t he s ubj ect’s visit or 
ass ess me nt. T he i nvesti gat or must verif y t hat all data e ntri es i n t he e C R F ar e acc ur ate 
a nd c orr ect. If s o me ass ess me nts ca nnot  be d o ne, or if certai n i nf or mati o n  is una vail a bl e, 
not  a p pli ca bl e or unkno w n,  t he Investi gat or  s ho ul d i ndi cate t his i n t he e C R F.  
C o mp uteri z e d  data -c hec k pr o gr a ms  a nd ma nual  c hec ks will i de ntif y a ny cli ni cal data 
dis cr e pa nci es f or r es ol uti o n . C orr es p o ndi ng q ueri es will be l oa de d i nt o t he s yste m  a nd 
t he site will be i nf or me d a b o ut ne w iss ues t o be r es ol ve d o n-li ne. All dis cr e pa nci es will 
be s ol ve d o n - li ne dir ectl y by t he Investi gat or  or b y a ut hori ze d staff. Off -li ne e dit c hec ks 
will be d o ne t o e xa mi ne  r el ati o ns hi ps o ver ti me a nd acr oss pa nels t o facilitate q ualit y 
data.  
After c o mpl eti o n, t he i nvesti gat or will be r e q uir e d t o el ectr o ni call y si gn off t he cli ni cal 
data . 
Data a b o ut all st ud y dr ugs  dis pe ns e d t o t he s ubj ect a nd a ny d os a ge c ha nges will be 
tr ac ke d o n t he e C R F.  
9. 3  
Access t o S o urce D at a  
D uri ng  t he st ud y, a mo nit or  will ma ke site visits t o r e vi e w pr ot oc ol c o mpli a nce, c o mpar e 
e C R F e ntri es  a nd i ndi vi d ual s ubj ect’s medi cal r ec or ds, ass ess dr ug acc o unta bilit y, a nd 
e ns ur e t hat  t he  st ud y  is bei ng  c o nd ucte d  acc or di ng t o perti ne nt  r e gul at or y  r e q uir e me nts . 
T he e C R F e ntri es will be verifi e d wit h s o ur ce d oc u me ntati o n. T he r e vi e w of me di cal 
r ec or ds will be perf or me d i n a ma nner t o e ns ur e t hat s ubj ect c o nfi de nti alit y is 
mai ntai ne d.  
C hec ki ng  of t he e C R F e ntri es  f or c o mpl ete ness a nd cl arit y, a nd cr oss-c hec ki ng  wit h 
s o ur ce d oc u me nts,  will be r e q uir e d t o mo nit or t he pr o gr ess of t he st ud y.  M or e o ver, 
Re gul at or y  A ut horiti es  of certai n c o untri es, I R Bs, I E Cs, a nd/ or t he S p o ns or’s Cli ni cal 
Q ualit y Ass ur a nce Gr o up ma y  wis h t o carr y o ut s uc h s o ur ce data c hec ks a nd/ or o n -site 
a udit i ns pecti o ns . Dir ect access t o s o ur ce data will be r e q uir e d f or t hes e i ns pecti o ns a nd 
a udits; t he y  wi ll be carri e d o ut gi vi ng d ue c o nsi der ati o n t o data pr otecti o n a nd me di cal 
c o nfi de nti alit y. T he I nvesti gat or  ass ur es  
  a nd t he S p o ns or of t he necess ar y 
s up p ort at all ti mes.  


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D at a Pr ocessi ng 
All data will be e nter e d b y s ite pers o nnel i nt o t he e C R F ( as detail e d i n Secti o n 9. 2. 1 ).  
T he data -r e vi e w a nd data-ha ndli ng  d oc u me nt,  t o be de vel o pe d d uri ng t he i niti ati o n p has e 
of t he st ud y,  will i ncl ude s pe cifi cati o ns f or c o nsiste nc y a nd pl a usi bilit y c hec ks o n data 
a nd will als o i ncl ude data - ha ndli ng  r ul es f or o b vi o us data err ors. Q uer y/ c orr ecti o n s heets 
f or unr es ol ve d q ueri es will be s e nt t o t he st ud y mo nit ors f or r es ol uti o n wit h t he 
I nvesti gat or. T he data b as e will be up date d o n t he basis of si gne d c orr ecti o ns .  
Pr e vi o us a nd c o nc o mita nt  me di cati o ns will be c o de d usi ng t he W orl d Healt h 
Or ga ni zati o n  ( W H O) Dr ug  Refer e nce List ( D R L), w hi c h e mpl o ys  t he A nat o mi cal 
T her a pe uti c C he mi cal ( A T C ) cl assifi cati o n s yste m. Me di cal hist or y/ c urr e nt  me di cal 
c o nditi o ns a nd A E s will be c o de d usi ng  t he Me d D R A  ter mi nol o gy. 
Pr e vi o us a nd c o nc o mita nt  dis eas es as w ell as A Es will be c o de d wit h Me d D R A . 
T he versi o ns of t he c o di ng di cti o nari es will be pr o vi de d i n t he Cli ni cal St ud y Re p ort . 
9. 5  
Arc hi vi ng  St u dy  Re c or ds  
Acc or di ng t o I nter nati o nal  C o nfer e nce o n Har mo ni zati o n  (I C H) gui deli nes, ess e nti al 
d oc u me nts  s ho ul d be r etai ne d f or a mi ni mu m  of 2 years after t he l ast a p pr o val of a 
mar keti ng  a p pli cati o n i n a n I C H  r e gi o n a nd until  t her e ar e no pe ndi ng or c o nte mpl ate d 
mar keti ng  a p pli cati o ns i n a n I C H r e gi o n or at l east 2  years ha ve el a ps e d si nce t he f or mal 
dis c o nti nuati o n  of cli ni cal de vel o p me nt of t he i nvesti gati o nal pr o d uct . H o w e ver, t hes e 
d oc u me nts  s ho ul d be r etai ne d f or a l o nger peri o d if r e q ui r e d b y t he a p pli ca bl e l e gal 
r e q uir e me nts. 
9. 6  
G o o d Cli nic al  Pr actice  
T he pr oce d ur es s et o ut i n t his st ud y pr ot oc ol ar e desi gne d t o e ns ur e t hat  t he S p o ns or a nd 
I nvesti gat or a bi de b y t he pri nci pl e s of t he G o o d Cli ni cal Pr acti ce gui deli nes of t he I C H, 
a nd of t he Decl ar ati o n of Helsi nki ( 1 9 9 6). T he st ud y  als o will be carri e d o ut i n kee pi ng 
wit h l ocal l e gal r e q uir e me nts .   
9. 7  
I nf or me d  C o ns e nt 
Bef or e eac h s ubj ect  is a d mitte d t o t he st ud y, i nf or me d c o ns e nt  will be o btai ne d fr o m t he 
s ubj ect ( or his/ her l e gall y a ut hori ze d  re pr es e ntati ve) a nd fr o m t he car e gi ver acc or di ng t o 
t he r e gul at or y  a nd l e gal r e q uir e me nts  of t he parti ci pati ng c o untr y. T his c o ns e nt  f or m 
must  be date d a nd r etai ne d b y t he I nvesti gat or as part of t he st ud y r ec or ds. T he 
I nvesti gat or will not underta ke  a ny  i n vesti gati o n s pecifi call y r e q uir e d o nl y f or t he 
cli ni cal st ud y until vali d c o ns e nt has bee n o btai ne d . T he ter ms  of t he  c o ns e nt  a nd w he n it 
w as o btai ne d must  als o be d oc u me nte d  i n t he e C R F. 
If a pr ot oc ol a me nd me nt  is r e q uir e d, t he i nf or me d  c o ns e nt f or m ma y nee d t o be r e vis e d 
t o r efl ect t he c ha nges t o t he pr ot oc ol. If t he c o ns e nt f or m is r e vis e d, it must  be r e vi e w e d 
a nd a p pr o ve d b y t he a p pr o pri ate I E C/I R B, a nd si gne d b y all s ubj ects s ubs e q ue ntl y 
e nr oll e d i n t he  st ud y  as w ell as t hos e c urr e ntl y  e nr oll e d i n t he st ud y. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
9. 8  
Pr ot oc ol  A p pr o v al  a n d  A me n d me nt  
Bef or e t he start of t he st ud y,  t he st ud y pr ot oc ol a nd/ or ot her r el e va nt d oc u me nts  will be 
a p pr o ve d b y t he I E C/I R B/ C o mpete nt  A ut horiti es, i n acc or da nce wit h l ocal l e gal 
r e q uir e me nts. T he S p o ns or must  e ns ur e t hat  all et hi cal a nd l e gal r e q uir e me nts ha ve bee n 
met bef or e t he first s ubj ect  is e nr oll e d i n t he st ud y. 
T his pr ot oc ol is t o be f oll o w e d e xactl y . T o alter t he pr ot oc ol, a me nd me nts  must  be 
writte n, r ecei ve a p pr o val fr o m t he a p pr o pri ate pers o nnel, a nd r ecei ve 
I R B/I E C/ C o mpete nt  A ut horit y  a p pr o val pri or t o i mpl e me ntati o n  (if a p pr o pri ate). 
F oll o wi ng a p pr o val, t he pr ot oc ol a me nd me nt(s)  will be s ub mitte d  t o t he I N D under 
w hi c h t he st ud y  is bei ng c o nd ucte d .  
A d mi nistr ati ve c ha nges ( not affecti ng  t he s ubj ect be nefit/r is k r ati o) ma y be ma de wit ho ut 
t he nee d f or a f or mal a me nd me nt. All a me nd me nts  will be distri b ute d t o all pr ot oc ol 
r eci pi e nts, wit h a p pr o pri ate i nstr ucti o ns. 
9. 9  
D at a a n d S af et y M o nit ori ng  B o ar d  
A D S M B  will be ass e mbl e d t o peri o di call y r e vi e w a nd e val uate acc u mul ate d  st ud y  data 
f or s ubj ect s afet y, st ud y c o nd uct a nd pr o gr ess. T he D S M B will ha ve t he r es p o nsi bilit y t o 
ma ke r ec o m me ndati o ns  c o ncer ni ng  c o nti nuati o n,  mo difi cati o n, or ter mi nati o n  of t he 
st ud y bas e d o n t heir i nde pe nde nt  e val uati o n of all st ud y r el ate d s afet y data. T he D S M B 
r ol e a nd acti viti es ar e des cri be d i n detail i n t he D S M B c harter. T he D S M B will c o nsist of 
a c hair pers o n a nd at l east 2  a d diti o nal me mbers ,  i ncl udi ng  1 statisti ci a n. 
9. 1 0  D ur ati o n  of t he  St u dy  
F or a n i ndi vi d ual s ubj ect, t he  ma xi mu m  d ur ati o n of t he  st ud y  f or eac h s ubj ect will be up 
t o 3 4 w ee ks (i ncl udi ng  up t o 4 w ee ks  f or s cr ee ni ng,  up t o 2 6 w ee ks of tr eat me nt  a nd up 
t o 4 w ee ks  f oll o w-up) .  
9. 1 1  Pre  mat ure   Te r mi nati o n  of t he  St u dy  
If t he I nvesti gat or, t he S p o ns or, or t he Me di cal M o nit or bec o mes a w ar e of c o nditi o ns or 
e ve nts t hat s uggest  a p ossi bl e hazar d t o s ubj ects if t he st ud y  c o nti nues,  t he  st ud y  ma y  be 
ter mi nate d after a p pr o pri ate c o ns ultati o n  bet w ee n t he r el e va nt parti es. T he st ud y  ma y 
als o be ter mi nate d  earl y at t he S p o ns or’s dis cr eti o n i n t he a bs e nce of s uc h  a fi ndi ng.  
C o nditi o ns  t hat  ma y  w arr a nt ter mi nati o n  i ncl ude, b ut  ar e not  li mite d t o:  
•  T he dis c o ver y of a n une xpecte d,  si gnifi ca nt,  or unacce pta bl e ris k t o t he s ubj ect s 
e nr oll e d i n t he st ud y.  
•  Fail ur e t o e nr oll s ubj ects at a n acce pta bl e r ate. 
•  A decisi o n o n t he part of t he S p o ns or t o s us pe nd or dis c o nti nue de vel o p me nt of t he 
dr ug.  
•  A r ec o m me ndati o n  fr o m t he D S M B t o ter mi nate  t he st ud y . 
If t he st ud y is ter mi nate d  pr e mat ur el y, all wit hdr a w n s ubj ects s ho ul d atte nd a fi nal visit 
wit h t he s a me pr oce d ur es as t he Wee k 2 6 visit.  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
9. 1 2  C o nfi de nti alit y  
All st ud y  fi ndi ngs  a nd d oc u me nts  will be r e gar de d as c o nfi de nti al . T he I nvesti gat or  a nd 
me mbers of his/ her r es ear c h tea m must  not dis cl os e s uc h i nf or mati o n  wit ho ut pri or 
writte n a p pr o val fr o m t he S p o ns or. 
T he a no ny mit y  of parti ci pati ng s ubj ects must  be mai ntai ne d. S ubj ect s will be i de ntifi e d 
o n e C R F a nd ot her d oc u me nts  s ub mitte d  t o 
  b y t heir s ubj ect nu mber,  i niti als 
a nd/ or birt h date, not b y na me. D oc u me nts  not  t o be s ub mitte d  t o  
  t hat 
i de ntif y  t he s ubj ect ( e. g., t he si gne d i nf or me d  c o ns e nt) must  be mai ntai ne d  i n c o nfi de nce 
b y t he I nvesti gat or.   
9. 1 3  Ot he r Et hic al a n d Re g ul at or y Iss ues  
If a si gnifi ca nt  s afet y iss ue is i de ntifi e d, eit her fr o m a n i ndi vi d ual cas e r e p ort or r e vi e w 
of a ggr e gate data, t he n t he S p o ns or will iss ue pr o mpt notifi cati o n t o all parti es – 
Re gul at or y  A ut horiti es , I nvesti gat ors, a nd I R B/I E Cs , as r e q uir e d. 
A si gnifi ca nt  s afet y iss ue is o ne t hat has a si gnifi ca nt  i mpact o n t he c o urs e of t he cli ni cal 
st ud y or pr o gr a m  (i ncl udi ng  t he p ote nti al f or s us pe nsi o n of  t he de vel o p me nt pr o gr a m or 
a me nd me nts  t o pr ot oc ols) or w arr a nts i m me di ate  up date of i nf or me d  c o ns e nt.  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1 0  R E F E R E N C E  LI S T  
 
1. W orl d Me di cal Ass oci ati o n Decl ar ati o n of Helsi nki. Rec o m me ndati o ns  gui di ng 
p hysi ci a ns i n bi o me di cal r es ear c h i nv ol vi ng hu ma n  s ubj ects. A d o pte d b y t he 1 8t h W M A 
Ge ner al Ass e mbl y, Helsi nki, Fi nl a nd, J une 1 9 6 4, a nd a me nde d b y t he 2 9t h W M A 
Ge ner al Ass e mbl y, T o kyo, J a pa n, Oct o ber 1 9 7 5 3 5t h W M A  Ge ner al Ass e mbl y, Ve ni c e, 
Ital y, Oct o ber 1 9 8 3 4 1st W M A Ge ner al Ass e mbl y, H o ng  K o ng, Se pte mber 1 9 8 9 4 8t h 
W M A Ge ner al Ass e mbl y, S o mers et West, Re p ubli c of S o ut h  Afri ca, Oct o ber 1 9 9 6  
2. Wil ki ns o n D., Wi ndf el d K, C ol di ng-J ør ge ns e n  E. 2 0 1 4. Safet y a nd effi cac y of 
i dal o pir di ne, a 5-H T 6 r ece pt or a nta go nis t,  i n pati e nts wit h mo der ate Al z hei mer’s dis eas e 
( L A D D E R): a r a nd o mis e d, d o ubl e- bli nd, pl ace b o-c o ntr oll e d p has e 2 tri al. La ncet Ne ur ol 
1 3: 1 0 9 2 – 9 9 
3. T he F o o d a nd Dr ug A d mi nistr ati o n  G ui da nce  f or I nd ustr y:  Al z hei mer’s  Dis eas e: 
De vel o pi n g Dr ugs f or t he Tr eat me nt  of Earl y Sta ge Dis eas e. Dr aft G ui da nce. Fe br uar y 
2 0 1 3. 
4. C o m mittee  f or Me di ci nal Pr o d ucts f or H u ma n  Us e [ C H M P] G ui deli ne o n Me di ci nal 
Pr o d ucts f or t he Tr eat me nt  of Al z hei mer’s Dis eas e a nd Ot her De me nti as. J ul y 2 0 0 8, 
C P M P/ E W P/ 5 5 3/ 9 5 Re v. 1 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1 1  A P P E N DI C E S  
 
A P P E N DI X   1: 
A L Z H EI M E R’ S  DI S E A S E A S S E S S M E N T  S C A L E - C O G NI TI V E  B E H A VI O R  
( A D A S-C o g ) 
 
Us e d wit h per missi o n fr o m t he NI A Alz hei mer’s Dis e as e C o o per ati ve St u dy  
 
 
 
A D A S I niti al  C o nve rs ati o n N ot es  
I nst r ucti o ns: 
For s pe cific i nst r ucti o ns  f or all t as ks, ref e r t o t he  A d mi nist r ati o n  M a n ual.  T he first 
s e ver al mi nutes  ar e s pe nt i n o pe n-e nde d c o nvers ati o n i n or der t o ass ess vari o us as pects of 
e xpr essi ve a nd r ece pti ve s peec h. T he n t he  re mai ni ng  c o gniti ve tests ar e a d mi nister e d. 
La ngua ge  a biliti es ar e e val uate d t hr o ugho ut  t he i nter vi e w a nd o n specifi c tests. Q uesti o ns 
eli citi ng “ yes ” a nd “ no” a ns w ers ass ess c o mpr e he nsi o n  o n a ver y basi c l e vel. Ot her  
q uesti o ns s ho ul d r e q uir e s pecifi c i nf or mati o n  a nd w ell -de vel o pe d c o m muni cati o n  s kills.  
E nga ge  t he s ubj ect i n a s hort c o nvers ati o n  a b o ut  ne ut r al t o pi cs (f or e xa mpl e: w eat her, t he 
s ubj ect's tri p t o t he cli ni c, or w hat t he s ubj ect ha d f or br ea kfast). T his c o nvers ati o n will 
hel p t o p ut t he s ubj ect at eas e bef or e t he  testi ng  be gi ns a nd will gi ve t he e xa mi ner  a n 
o p p ort unit y  t o o bs er ve ho w w ell t he s ubj ect ca n us e a nd understa nd   la ngua ge.  T her e ar e 
t hr ee cli ni cal r ati ngs of l a ngua ge  a bilit y o n t he c o gniti ve part of t he A D A S . Us e t his pa ge 
t o rec or d yo ur i nter vi e w notes. D oc u me ntati o n  s ho ul d be e vi de nt o n t his f or m t o s up p ort 
r ati ng  of s p o ke n  l a ngua ge  abilit y, w or d fi ndi ng  diffi c ult y  a nd c o mpr e he nsi o n.  A ny  r ati ng 
of i mpair me nt  s ho ul d be s up p orte d b y notes  doc u me nte d  o n t his pa ge.  
P ossi bl e 
T o pi cs: 
Weat her  
Br ea kfast  
Cli ni c tri p  
Ot her  
1)  C o mpr e he nsi o n 
 
 
2)  W or d fi ndi ng  
 
 
3)  S p o ke n  l a ngua ge  
 
 
Testi ng  C o m me nts:  
 
 
 
1.  
W O R D R E C A L L  T A S K  ( Wor d  List 1): 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T o be gi n  testi ng,  s a y: “I a m g oi ng t o s ho w y o u s o me w or ds pri nt e d  o n t hes e w hit e 
c ar ds. Ple as e re a d e ac h w or d o ut l o u d  a n d t r y t o re me m be r  it, be c a us e l at e r I will 
as k y o u t o t r y t o re me m be r  all of t he w or ds I ha ve s ho w n y o u. Re a dy, re a d t he w or d 
a n d t r y t o re me m be r  it. ”  
Pr es e nt eac h w or d t o t he s ubj ect a nd as k hi m/ her t o s a y it al o ud. After all 1 0 w or ds ha ve 
bee n pr es e nte d, s a y: “ G o o d, no w t ell me all t he w or ds y o u c a n re me m be r  t hat we re 
o n t hat list. ” Pr o mpt  wit h  “ A ny ot he rs ?” as necess ar y. F or tri als 2 a nd 3 s a y:  “ N o w I 
a m g oi ng t o s ho w y o u t hat s a me list a g ai n. Re a d e ac h w or d o ut l o u d  a n d t r y t o 
re me m be r it. ”  Ex a mi ner s h o ul d c heck a r es p o ns e (yes/ n o) f or ever y w or d.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If a ny  tri al not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne):  
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, e nt e r a s c ore of “ 1 0 ” i n e C R F) 
 
2.  
C O M M A N D S:  
T his tas k is desi gne d t o ass ess r ece pti ve s peec h. T he s ubj ect is as ke d t o carr y o ut fi ve 
s e par ate c o m ma nds  wit h 1 t o 5 ste ps per c o m ma nd.  Eac h c o m ma nd  s ho ul d be r ea d o nce. 
If t he s ubj ect d oes not r es p o nd or l o o ks c o nf us e d, or as ks f or a r e petiti o n, t he e xa mi ner 
s ho ul d gi ve t he e ntir e c o m ma nd  o ne mor e ti me. T he n go o n t o t he ne xt  c o m ma nd.  All 
Tri al  1  
Wo r d 
rec alle d 
c o rrectl y ? 
Yes  
N o 
B utter 
 
 
Ar m  
 
 
S h ore 
 
 
Letter 
 
 
Q uee n 
 
 
Ca bin 
 
 
P ole  
 
 
Tic ket  
 
 
Grass 
 
 
E n gine 
 
 
Tot al N ot 
Rec alle d 
 
 
Tri al  2 
Wo r d 
rec alle d 
c o rrectl y ? 
Yes  
N o 
P ole  
 
 
Letter  
 
 
B utter  
 
 
Q uee n 
 
 
Ar m  
 
 
S h ore 
 
 
Grass 
 
 
Ca bin 
 
 
Tic ket  
 
 
E n gine 
 
 
Tot al N ot 
Rec alle d 
 
 
Tri al  3 
Wo r d 
rec alle d 
c o rrectl y ? 
Yes  
N o 
S h ore 
 
 
Letter 
 
 
Ar m  
 
 
Ca bin 
 
 
P ole  
 
 
Tic ket  
 
 
E n gine 
 
 
Grass 
 
 
B utter 
 
 
Q uee n 
 
 
Tot al N ot 
Rec alle d 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
c o m ma nds  s ho ul d be gi ve n t o e ver y s ubj ect. E xa mi ner s ho ul d c hec k a r es p o ns e ( yes/ no)  
f or e ver y c o m ma nd. 
T o be gi n  testi ng,  s a y: “ N o w I a m g oi ng t o as k y o u t o do a f e w t hi ngs.  First... ”  
C o m m a n d 
C o m m a n d 
perf o r me d 
c o rrectl y ? 
Yes  
N o 
a.  “ Ma ke a fist. ” (sa y “Rel a x it ” if nee de d u p o n c o m pletio n).  
 
 
b.  “ P oint t o t he ceili n g, a n d t he n t o t he fl o o r. ” 
 
 
Li ne u p a pe ncil, watc h a n d c ar d  (left t o ri g ht fro m s u bject’s p oi nt of vie w) o n t he t a ble.  
c.  “ P ut t he pe ncil o n t o p of t he c ar d  a n d t he n p ut it b ac k . ” 
 
 
d.  “ P ut t he watc h  o n t he ot her si de of t he pe ncil  a n d t ur n o ver t he 
c ar d. ” 
 
 
e.  “ T a p e ac h s h o ul der t wice   wit h t wo fi n gers, kee pin g  y o ur e yes s h ut . ” 
 
 
If tas k not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne):  
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, circle “ 5 ” o n t he s c ori ng t a ble 
be l o w ) 
Sc ori ng:  ( circle o ne)  
0 
= all c o m ma nds  c orr ect 
1 
= 1 c o m ma nd  i nc orr ect  
2 
= 2 c o m ma nds  i nc orr ect  
3 
= 3  c o m ma nds  i nc orr ect 
4 
= 4  c o m ma nds  i nc orr ect 
5 
= 5  c o m ma nds  i nc orr ect 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 8  of 1 4 3  
0 2 Mar c h 2 0 1 6  
3.  
C O N S T R U C TI O N A L  P R A XI S:  
T his test ass ess es t he s ubj ect’s a bilit y t o c o p y 4 ge o metri c f or ms. T he f or ms s ho ul d be 
pr es e nte d o ne at a ti me. If t he s ubj ect l o o ks c o nf us e d or diss atisfi e d wit h t he dr a wi ng, or 
as ks t o tr y a gai n, t he s ubj ect s ho ul d be all o w e d a s e c o n d  att e  m pt  f or eac h sha pe. If a 
s ec o nd atte mpt is ma de, as k t he s ubj ect t o i ndi cate w hi c h o ne is better, a nd s c or e o nl y 
t hat  atte mpt. Ex a mi ner s h o ul d c heck a r es p o ns e (yes/ n o) f or ever y f or m.  
T o be gi n  testi ng,  s a y: “ O n t his pie ce of pa pe r is a s ha pe. Tr y t o dr a w a not he r o ne 
t hat l o o ks j ust li ke t his, s o me w he re o n t he pa ge. ” 
Fi g ure  
Fi g ure  dra w n  
c o rrectl y ? 
Yes  
N o 
a.  Circle  
A close d c ur ve d figure.  S mall  ga ps d o n ot c o u nt as err ors. Size is n ot 
critical.  
 
 
b.  T wo o verl a p pi n g rect a n gles  
Figures  m ust be f o ur -side d, a n d o verla p  m ust be si milar  t o prese nte d 
f or m. C ha n ges in size are n ot sc ore d.  
 
 
c.  Di a m o n d ( R h o m b us)  
Figure m ust be f o ur -side d, orie nte d  s o t hat t he p oints are at t he t o p a n d 
b ott o m, a n d t he sides a p pr o xi mately  e q ual in le n gt h  (e. g., lo n gest  side is 
n ot > 1. 5 ti mes t he le n gt h  of t he s h ortest side).  
 
 
d.  C u be  
T he figure  is 3 -di me nsio nal,  wit h fr o nt face in t he c orrect orie ntatio n, 
inter nal  lines dra w n c orrectly  bet wee n c or ners. O p p osite sides  of faces 
s h o uld be a p pr o xi mately parallel. 
 
 
e.  N o figures  dra w n; scrib bles;  parts of f or ms; w or ds instea d of f or m  
 
 
If tas k not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne): 
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, circle “ 5 ” o n t he s c ori ng t a ble 
be l o w ) 
Sc ori ng:  ( circle o ne)  
0  
= all 4 dr a wi ngs c orr ect  
1  
= 1 f or m dr a w n i nc orr ectl y 
2  
= 2 f or ms dr a w n i nc orr ectl y 
3  
= 3  f or ms dr a w n i nc orr ectl y 
4  
= 4  f or ms dr a w n i nc orr ectl y 
5  
= no fi gur es dr a w n; s cri b bl es; parts of f or ms;  w or ds i nstea d of f or ms  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
6 9  of 1 4 3  
0 2 Mar c h 2 0 1 6  
4.  
N A MI N G  O B J E C T S / FI N G E R S:  
F or t his tas k, t he s ubj ect is as ke d t o na me  1 2 r a nd o ml y pr es e nte d r eal o bj ects. O bj ects 
s ho ul d be pr es e nte d i n r a nd o m or der. Gi ve t he s ubj ect i nstr ucti o ns  si mil ar t o t he 
f oll o wi ng: “ N o w I a m g oi ng t o s ho w y o u s o me o bj e cts. I w a nt y o u t o t ell me w hat 
t he ir na mes are. W hat is t his c alle d? ”  ( pr es e nt o bj ect). If t he s ubj ect r es p o nds wit h t he 
o bj ect’s f uncti o n  s a y: “ Yes, t hat's w hat it does, b ut w hat is its na me ? ”  If t he s ubj ect 
d oes not r es p o nd, t he e xa mi ner s ho ul d gi ve t he s e ma nti c c ue f or t hat ite m ( pr o vi de d 
bel o w). If t he s ubj ect still d oes not r es p o nd or ma kes a n err or, pr ocee d t o t he ne xt o bj ect. 
Ex a mi ner s h o ul d c heck a r es p o ns e (yes/ n o) f or ever y o bj ect/fi n ger.  
 
It e m 
Acce pt a ble  Cl ue  
Re s po ns e  
c orre ct ?  
Ye s  
N o  
Fl o w er  
gr o ws i n gar de n  
 
 
Be d  
us e d f or sl ee pi ng 
 
 
W histl e  
ma kes  a s o und  w he n yo u  bl o w o n it  
 
 
Pe ncil  
us e d f or writi ng  
 
 
Rattl e  
a ba b y’s t o y 
 
 
Mas k  
hi des yo ur  face  
 
 
Sciss ors  
c uts pa per  
 
 
C o mb  
us e d o n hair  
 
 
Wall et  
hol ds yo ur  mo ne y  
 
 
Har mo ni ca  
a musi cal i nstr u me nt 
 
 
Stet hos c o pe 
d oct or us es it t o liste n t o yo ur  heart  
 
 
T o ngs  
pi c ks up f o o d 
 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 0  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T he s ubj ect is als o as ke d t o na me  t he  fi ngers  o n his/ her d o mi na nt  ha nd.  Sa y: “ Ple as e 
pl ace y o ur ri g ht  ( or left) ha n d  o n t he t a ble. N o w I a m g oi ng t o poi nt  t o a part of 
y o ur  ha n d  a n d  I w a nt  y o u  t o t ell me w hat  it’s c alle d. W hat  is t his ? ” If  a q uer y is 
necess ar y s a y: “ W hat is a not he r na me f or t his fi nge r ? ”  
 
Fi nge rs  
Res po ns e c orre ct ?  
Ye s  
N o  
T hu mb  
 
 
I nde x/ P ointer/ F or efi nger  
 
 
Mi d dl e 
 
 
Ri ng  
 
 
Pi nky/ Littl e/ Ba b y  
 
 
If tas k not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne): 
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, circle “ 5 ” o n t he s c ori ng t a ble 
be l o w ) 
Sc ori ng:  ( circle o ne)  
0 
= 0 -2 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y  
1 
= 3 -5 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y  
2 
= 6 -8 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y  
3 
= 9 - 1 1 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y 
4 
= 1 2 - 1 4 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y 
5 
= 1 5 - 1 7 ite ms ( o bj ects a nd fi ngers) na me d i nc orr ectl y 
 
5.  
I D E A Tl O N A L  P R A XI S: 
T his tas k is desi gne d t o deter mi ne w het her t he s ubj ect ca n perf or m a fa mili ar b ut 
c o mpl e x s e q ue nce of acti o ns. T her e ar e 5 c o mp o ne nts  t o t his tas k.  Pl ace a bl a nk l o ng 
e nvel o pe, a n 8 ½" × 1 1" s heet of pa per a nd a pe ncil i n fr o nt of t he s ubj ect. 
Rea d t he f oll o wi ng i nstr ucti o n  t o t he s ubj ect e xactl y as writte n: “I  w a nt  y o u  t o pre t e n d 
y o u ha ve writt e n y o urs elf a lett e r. T a ke t his p ie ce of pa pe r, f ol d it s o t hat it will  fit 
i nt o  t he  e nve l o pe , a n d t he n p ut  it i nt o  t he  e nve l o pe . T he n, s e al t he e nvel o pe , a d dre ss 
t he e nvel o pe t o y o urs elf, a n d s ho w me w he re t he st a m p g oes. ” 
If t he s ubj ect f or gets part of t he tas k, or is ha vi ng  diffi c ult y, t he tester s ho ul d r e peat t he 
i nstr ucti o n  f or t he  c o mp o ne nt  of t he tas k w her e t he  s ubj ect is ha vi ng  diffi c ult y.  After  t he 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
first c o mpl ete i nstr ucti o n,  o nl y  o ne a d diti o nal r e mi nder s ho ul d be give n f or eac h 
c o mp o ne nt. Ex a mi ner s h o ul d c heck a r es p o ns e (yes/ n o) f or ever y c o m p o ne nt.  
C o m po ne nt  
Acti o n  c orre ct ?  
Ye s  
N o  
a. F ol ds pa per  
 
 
b.  P ut pa per i n e nvel o pe  
 
 
c. Seal e nvel o pe  
 
 
d.  A d dr ess e nvel o pe 
 
 
e. I ndi cate w her e sta mp goes 
 
 
If tas k not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne):  
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, circle “ 5 ” o n t he s c ori ng t a ble 
be l o w ) 
Sc ori ng:  ( circle o ne)  
0 
= all c o mp o ne nts  perf or me d c orr ectl y  
1 
= fail ur e t o perf or m 1 c o mp o ne nt 
2 
= fail ur e t o perf or m 2 c o mp o ne nts 
3 
= fail ur e t o perf or m 3 c o mp o ne nts 
4 
= fail ur e t o perf or m 4 c o mp o ne nts 
5 
= fail ur e t o perf or m  5 c o mp o ne nts 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
6.  
O RI E N T A TI O N:  
T his tas k is desi gne d t o deter mi ne ho w w ell ori e nte d t he s ubj ect is wit h r e gar d t o ti me 
a nd pl ace. As k t he s ubj ect f or eac h of t hes e pi eces of i nf or mati o n o ne at a ti me . O ne 
r estate me nt  of eac h q uesti o n is all o w e d ( e. g. if s ubj ect c o nf us es da y a nd date.) Q uesti o ns 
must  not be r estate d bas e d o n a n i nc orr ect r es p o ns e b ut o nl y if t he s ubj ect d oes not 
understa nd  t he i niti al q uesti o n  or as ks f or a r e petiti o n. Ex a mi ner s h o ul d c heck a r es p o ns e 
(yes/ n o) f or ever y q uesti o n. 
Q ue sti o n  
Res po ns e c orre ct ?  
Ye s  
N o  
F ull na me: ( must  be e xact)  
 
 
M o nt h:  ( must  be e xact)  
 
 
Date: ( ± 1 da y)  
 
 
Year: ( must  be e xact)  
 
 
Da y of t he w ee k: ( must  be e xact)  
 
 
Seas o n: ( wit hi n 1 w ee k of upc o mi ng  s eas o n or wit hi n 2 w ee ks of 
pr e vi o us s eas o n) 
 
 
Pl ace: ( parti al na mes ar e acce pta bl e, b ut ge neri c ter ms ar e not)  
Sa y: “ W he re are we no w ? ”  or “ W hat  is  t he  na me   of t his 
pl ace ? ”  
 
 
Ti me: ( ± 1 ho ur)  
Sa y: “ Wit ho ut  l o o ki ng at y o ur w at c h, t ell me 
a p pr o xi mat el y  w hat ti me it is. ”  
 
 
If tas k not a d mi nister e d, pl eas e s pecif y r eas o n ( c hec k o ne):  
☐ N ot d o ne (f or r eas o ns ot her t ha n p hysi cal/ c o gniti ve i mpair me nt)  
☐ S ubj ect r ef us e d  
☐ S ubj ect una bl e f or p hysi cal r eas o ns  
☐ S ubj ect una bl e f or c o gniti ve r eas o ns (if s ele ct e d, circle “8 ” o n t he s c ori ng t a ble 
be l o w ) 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Sc ori ng:  ( circle o ne)  
0 
= all r es p o ns es c orr ect 
1 
= 1 r es p o ns e i nc orr ect  
2 
= 2 r es p o ns es i nc orr ect  
3 
= 3 r es p o ns es i nc orr ect  
4 
= 4  r es p o ns es i nc orr ect 
5 
= 5  r es p o ns es i nc orr ect 
6 
= 6  r es p o ns es i nc orr ect 
7 
= 7  r es p o ns es i nc orr ect 
8 
= 8  r es p o ns es i nc orr ect 
 




S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
 
8. 
R E M E M B E RI N G  T E S T I N S T R U C TI O N S  
T his ite m e val uates t he s ubj ect’s a bilit y t o r e me mber t he r e q uir e me nts of t he Wor d 
Re c o g niti o n  t as k. T he nu mber  of r e mi nders gi ve n  o n t he  W or d Rec o gniti o n  tas k ar e 
c o unte d t o r ate t his ite m. If t he W or d Rec o gniti o n  tas k w as not c o mpl ete d or not 
atte mpte d, t he n  t his ite m  must  not be s c or e d. 
Eac h i nsta nce of me mor y  fail ur e f or t he test i nstr ucti o ns  after t he first t w o ite ms is 
s c or e d. 
Sc ori ng:  ( circle o ne)  
0 
N o ne  = s ubj ect ne ver nee ds e xtr a r e mi nders of 
i nstr ucti o ns 
1 
Ve r y mil d  = f or gets  o nce  
2 
Mil d  = must   be r e mi nde d 2 ti mes 
3 
M o de r at e  = must  be r e mi nde d 3 or 4 ti mes 
4 
M o de r at el y s e ve re  = must  be r e mi nde d 5 or 6 ti mes 
5 
Se ve re  = must  be r e mi nde d 7 or mor e ti mes 
 
9. 
C O M P R E H E N SI O N:  
T his ite m e val uates t he s ubj ect’s a bilit y t o understa nd s peec h. T o r ate t his ite m c o nsi der 
ho w w ell t he s ubj ect w as a bl e t o understa nd  t he e xa mi ner’s s peec h d uri ng t he o pe ni ng 
dis c ussi o n a nd  d uri ng  t he  test  s essi o n. D o n ot  c o u nt perf or m a nce o n C o m m a n ds s u bt est 
w he n r ati n g t his it e m.  
Sc ori ng:  ( circle o ne)  
0 
N o ne  = s ubj ect understa nds  
1 
Ve r y mil d  = 1 or 2 i nsta nces of  mis understa ndi ng  
2 
Mil d  = 3 - 5 i nsta nces of mis understa ndi ng 
3 
M o de r at e  = r e q uir es s e ver al r e petiti o ns a nd r e p hr asi ng 
4 
M o de r at el y s e ve re  = s ubj ect o nl y occasi o nall y r es p o nds c orr ectl y; 
i.e., yes/ no q uesti o ns  
5 
Se ve re  = s ubj ect r ar el y r es p o nds t o q uesti o ns 
a p pr o pri atel y, not d ue t o p o vert y of s peec h 
 
1 0. 
W O R D FI N DI N G  DI F FI C U L T Y: 
 
T o r ate t his ite m, t he e xa mi ner must  deter mi ne w het her t he s ubj ect has di ffi c ult y  i n 
fi ndi ng  t he desir e d w or d i n s p o nta ne o us  s peec h d uri ng  t he i nter vi e w a nd test s essi o n.  
D o n ot c o u nt perf or m a nce o n N a mi n g O bj ects a n d Fi n gers s u bt est w he n r ati n g t his 
it e m. D oc u me ntati o n  s ho ul d be e vi de nt o n  Pa ge 1 t o s up p ort a ny r ati ng a b o ve zer o. 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
7 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Sc ori ng:  ( circle o ne)  
0 
N o ne  = no e vi de nce of w or d fi ndi ng  diffi c ult y  i n 
s p o nta ne o us  s peec h 
1 
Ve r y mil d  = 1 or 2 i nsta nces, not cli ni call y si gnifi ca nt  
2 
Mil d  = noti cea bl e cir c u ml oc uti o n  or s yno ny m 
s ubstit uti o n 
3 
M o de r at e  = l oss of w or ds wit ho ut c o mpe ns ati o n  o n 
occasi o n  
4 
M o de r at el y s e ve re  = fr e q ue nt  l oss of w or ds wit ho ut c o mpe ns ati o n 
5 
Se ve re  = nearl y t otal l oss of c o nte nt of w or ds; s peec h 
s o unds  e mpt y;  1-2 w or d utter a nces  
 
1 1. 
S P O K E N  L A N G U A G E  A BI LI T Y :  
T his ite m is a gl o bal r ati ng of t he q ualit y of s peec h, i.e., cl arit y, diffi c ult y i n ma ki ng 
o nes elf underst o o d. I n r ati ng t his ite m t he e xa mi ner s ho ul d c o nsi der all of t he s peec h 
pr o d uce d b y t he  s ubj ect i n t he i niti al  i nter vi e w a nd t he test s essi o n. D oc u me ntati o n 
s ho ul d be e vi de nt o n Pa ge 1 t o s up p ort a ny r ati ng a b o ve zer o. ( Refer t o t he pr oce d ur es 
ma nual  f or gui deli nes)  
Sc ori ng:  ( circle o ne)  
0 
N o ne  = no i nsta nces w her e it is diffi c ult t o understa nd 
t he s ubj ect 
1 
Ve r y mil d  = o ne i nsta nce of l ac k of understa nda bilit y 
2 
Mil d  = s ubj ect has diffi c ult y  l ess t ha n  2 5 % of t he ti me 
3 
M o de r at e  = s ubj ect has diffi c ult y  2 5-5 0 % of t he ti me  
4 
M o de r at el y s e ve re  = s ubj ect has diffi c ult y  mor e t ha n  5 0 % of t he ti me 
5 
Se ve re  = o ne or t w o w or d utter a nce;  fl ue nt, b ut e mpt y 
s peec h; mute 
 
 
 
















S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
8 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
C LI NI C A L D E M E N TI A R A TI N G ( C D R)  
0 
0. 5  
1 
2 
3 
 
 
I m p air me nt 
 
N o ne  
0 
Q ue s ti o n a ble  
0. 5  
Mil d  
1 
M o de r ate  
2 
Se v e re  
3 
M e  m o r y  
N o me m or y loss  or slig ht 
inc o nsiste nt  f or getf ulness 
C o nsiste nt  slig ht 
f or getf ulness;  partial 
re c olle ctio n  of e ve nts; 
“ be nig n”  f or getf ulness  
M o derate me m or y  loss; 
m ore mar ke d f or re c e nt 
e ve nts; defe ct interferes wit h 
e ver y da y a ctivities  
Se vere me m or y  loss;  o nly 
hig hly  le ar ne d  material 
retaine d; ne w material 
ra pidly  lost   
Se vere me m or y  loss;  o nly 
fra g me nts re main 
O rie nt ati o n  
F ully  orie nte d  
F ully  orie nte d  e xc e pt f or  
slig ht  diffic ult y  wit h  ti me 
relatio ns hips 
M o derate diffic ult y  wit h  
ti me  relatio ns hips;  orie nte d 
t o pla c e of e xa minatio n;  ma y 
ha ve ge o gra p hic  
dis orie ntatio n  els e w here  
Se ve re diffic ult y  wit h  ti me 
relatio ns hips;  us ually 
dis orie nte d  t o  ti me,  ofte n t o 
pla c e  
Orie nte d  t o  pers o n o nly  
J u d g me nt  & 
Pr o ble  m  S ol vi n g  
S olves  e ver y da y pr o ble ms 
a n d ha n dles  b usiness  a n d 
fina nc ia l  a ffa irs w e ll; 
ju d g me nt g o o d  in  relatio n  t o 
past  perf or ma nc es  
Slig ht  i m pair me nt  in  s olvin g 
pr o ble ms,  si mila rit ie s  a n d 
differe nc es  
M o derate diffic ult y  in 
ha n dlin g  pr o ble ms, 
si milarities  a n d differe nc es; 
s oc ia l ju d g me nt us ually   
maintaine d  
Se verely  i m pa ire d  in 
ha n dlin g  pr o ble ms, 
si milarities  a n d differe nc es; 
s oc ia l ju d g me nt us ually 
i m pa ire d 
U na ble  t o ma ke ju d g me nts 
or s olve  pr o ble ms  
C o m m u nit y 
Affairs  
I n de pe n de nt  f u nctio n  at 
us ual  le vel  in  jo b,  s h o p pin g, 
v olu nte er  a n d  s ocial  gr o u ps  
 
Slig ht  i m pa ir me nt  in  t hes e 
a c tivitie s  
U na ble  t o f u nctio n 
in de pe n de ntly  at t hes e 
a c tivitie s  a lt h o u g h  ma y  still 
be e n ga ge d  in  s o me;  a p pe ars 
n or mal  t o  c as ual ins pe ctio n  
N o prete ns e of in de pe n de nt  f u nctio n  o utside  h o me  
A p pe ars w ell  e n o u g h  t o  be 
ta ke n t o  f u nctio ns  o utside 
t he fa mily  h o me  in de pe n de nt 
f u nctio n 
A p pe ars t o o  ill  t o be ta ke n t o 
f u nctio ns  o utside  t he fa mily 
h o me  
H o me  & 
H o b bie s  
Life  at h o me,  h o b bies  a n d 
inte lle c t ua l  inte re sts  w e ll 
maintaine d  
 
Life  at h o me,  h o b bies  a n d 
inte lle c t ua l  inte re st  slig htly 
i m pa ire d 
Mild  b ut de finite  i m pa ir me nt 
of f u nctio n  at h o me  m ore 
diffic ult  tas ks a ba n d o ne d; 
m ore  c o m plic ate d  h o b bies 
a n d interests  a ba n d o ne d 
O nly  si m ple  tas ks pres er ve d; 
ver y  restricte d interests, 
p o orly  maintaine d  
N o sig nific a nt  f u nctio n  in 
h o me   
Pe rs o n al C are  
F ull  c a pa ble of  s e lf -c are  
N e e ds pr o m ptin g  
Re q uires assista nc e in 
dressin g,  h y gie ne,  ke e pin g 
of pers o nal  effe cts  
Re q uires  m uc h  help  wit h 
pers o nal  c are; fre q ue nt 
inc o ntine nc e 
Sc ore o nly as decline  fr o m pre vio us  us ual le vel  d ue t o c o gnitive  loss, n ot i m pair me nt  d ue t o ot her fact ors.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
8 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 3: 
MI NI -M E N T A L  S T A T E E X A MI N A TI O N  
M a xi  m u m 
Sc o r e  
P ati e nt’s 
Sc o r e  
Q uesti o ns  
5 
 
“W hat  is t he ( ye ar)  (s e as o n) ( dat e) ( da y) ( m o nt h) ?” 
5  
 
“W her e ar e we: ( c o u ntr y) ( cit y) ( part of cit y) ( n u m ber of fl at/ h o us e) ( na me of 
str e et) ?” 
3  
 
The e xa mi ner  na mes t hr e e u nr el at e d o bj e cts cl earl y a n d sl o wl y, t he n as ks t he 
pati e nt t o na me all t hr e e of t he m. The pati e nt’s r es p o ns e is us e d f or s c ori n g. The 
r at er r e pe ats t he m u ntil pati e nt l e ar ns all of t he m if p ossi bl e. N u m ber of tri als: 
_ _  
5  
 
“I  wo ul d li ke y o u t o c o u nt bac k war d fr o m 1 0 0 b y s e ve ns”  
( 9 3, 8 6, 7 9, 7 2, 6 5, …). St o p aft er 5 a ns wers. 
3  
 
“ Earli er I t ol d y o u t he na me of t hr e e t hi n gs. Ca n y o u t ell me what  t h os e wer e ?”  
2  
 
S h o w t he pati e n t t wo si m pl e o bj e cts, s uc h as a wrist wat c h a n d a pe ncil a n d as k 
t he pati e nt t o na me t he m.  
1 
 
“Re pe at t he p hr as e: ' N o ifs, a n ds or b uts'  ” 
3  
 
“ Ta ke  t he pa per i n y o ur ri g ht ha n d,  f ol d it i n half a n d  p ut it o n t he fl o or ”  
( The r at er gi ves t he pati e nt a pi e c e of bl a n k pa per.) 
1 
 
“ Pl e as e r e a d t his a n d d o what  it s a ys: ” 
( Writt e n i nstr ucti o n is “ Cl os e y o ur e yes ”.) 
1 
 
“Ma ke u p a n d  writ e a s e nt e nc e a b o ut a n yt hi n g. ” 
( This s e nt e nc e m ust c o nt ai n a n o u n a n d a ver b.) 
1  
 
“ Pl e as e c o p y t his pi ct ur e.” 
( The r at er gi ves t he pati e nt a bl a n k pi e c e of pa per a n d as ks hi m/ her t o dr a w  t he 
s y m b ol bel o w. All 1 0 a n gl es m ust be pr es e nt a n d t wo m ust i nt ers e ct.)  
 
 
3 0  
 
T O T A L  
 
 
 


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A P P E N DI X 4: 
A L Z H EI M E R’ S  DI S E A S E C O -O P E R A TI V E  S T U D Y  A C TI VI T Y  O F D AI L Y 
LI VI N G  
 
N O T E S:  
( 1) { P } r efers t o t he parti ci pa nt a nd s ho ul d be r e pl ace d by t he parti ci pa nt's na me or 
r el ati o ns hi p t o t he st ud y  part ner eac h ti me a n A D L q uesti o n is as ke d of t he st ud y part ner. 
( 2) T his A D L  i nve nt or y  must  be gi ve n  i n t he  f or mat  of a n i nter vi e w of t he st ud y  part ner, 
eit her dir ectl y or b y tel e p ho ne.  T he f or m  s ho ul d  N O T be gi ve n t o a st ud y part ner t o 
c o mpl ete o n his/ her o w n.  
R E A D  T H E F O L L O WI N G  I N S T R U C TI O N S  T O T H E S T U D Y  P A R T N E R:  
I a m goi ng  t o as k yo u a b o ut a nu mber  of dail y acti viti es t hat { P } ma y  ha ve perf or me d 
d uri ng t he past 4 w ee ks. Pl eas e tell me a b o ut { P }'s act u al perf or ma nce, not a b o ut w hat 
he/s he c o ul d ha ve d o ne if a n o p p ort unit y  ha d aris e n. F or eac h acti vit y t hat { P } atte mpte d, 
I' m  goi ng  t o as k yo u  t o c ho os e o ne o ut  of a nu mber  of des cri pti o ns t hat  best fits his/ her 
most us ual perf or ma nce.  
F or s o me acti viti es,  I'll as k a b o ut w het her { P } perf or me d i nde pe nde ntl y,  or wit h 
s uper visi o n or hel p. Let me e xpl ai n ho w w e ar e defi ni ng  t hes e w or ds:  
•  I n de pe n de ntl y mea ns t hat { P } c o mpl ete d t he acti vit y wit ho ut bei ng hel pe d. We still 
c o nsi der it i nde pe nde nt  if { P } w as r e mi nde d  or pr o mpte d t o get starte d, or r ecei ve d a 
littl e pr o mpti ng  w hil e perf or mi ng  t he acti vit y. 
•  Wit h  s u pe r visi o n  mea ns t hat { P } r e q uir e d ver bal r e mi nders a nd i nstr ucti o ns w hil e 
d oi ng  t he acti vit y.  
•  Wit h  he l p  mea ns t hat { P } w as gi ve n s o me de gr ee of p hysi cal assis ta nce b y a not her 
pers o n t o perf or m t he acti vit y.  
 
I N S T R U C TI O N S  F O R T H E  R A T E R: 
If t he  st ud y  part ner states t hat  { P } ha d  no o p p ort unit y  t o perf or m t he  tas k duri ng  t he  past 
f o ur w ee ks ( e. g., { P } di d not ha ve access t o a tel e p ho ne, t her ef or e c o ul d not p ossi bl y 
ma ke p ho ne calls), t he r es p o ns e s ho ul d be r ec or de d as ' no.' 
If eit her t he st ud y  part ner's a ns w er or t he q uesti o nnair e is uncl ear, pl eas e ma ke notes o n 
t he cas e r e p ort f or m detaili ng t he pr o bl e m. 
F or q uesti o ns r e gar di ng s pecifi c A D L ite ms, pl eas e r efer t o t he A D L Res p o ns e Car d. 
I nst r ucti o ns:  F or eac h q uesti o n, us e t he s ubj ect's na me w her e { P } a p pears.  
Bef or e be gi nni ng,  r ea d t he q uesti o nnair e  gui deli nes t o t he  i nf or ma nt.  
 


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1. 
Re gar di ng e ati ng, whi c h best des cri bes { P } us ua l perf or ma nce d uri ng  t he past 
4 w ee ks ? 
3 ☐ ate wit h o ut p h ysical  help, a n d use d a k nife  
2 ☐ use d a f or k or s p o o n, b ut n ot a k nife, t o eat  
1 ☐ use d fin gers  t o eat  
0 ☐ us ually  or al wa ys was fe d b y s o me o ne else  
2. 
Re gar di ng w al ki ng  ( or getti ng  ar o und  i n a w heel c hair), i n t he past 4 w ee ks, w hi c h 
best des cri bes his/ her o pti mal  pe rf or ma nce : 
3 ☐ m o bile  o utside  of h o me wit h o ut p h ysical  help  
2 ☐ m o bile  acr oss a r o o m wit h o ut  p h ysical  help  
1 ☐ tra nsferre d fr o m be d t o c hair wit h o ut help 
0 ☐ re q uire d p h ysical  help t o walk or tra nsfer 
3. 
Re gar di ng b o w el a nd bl a d der f uncti o n at t he t oilet , w hi c h best des cri bes his/ her 
us ual  perf or ma nce i n t he past 4 w ee ks:  
3 ☐ did e ver yt hin g  necessar y wit h o ut  s u per visio n  or p h ysical help  
2 ☐ nee de d s u per visio n,  b ut n o p h ysical  help  
1 ☐ nee de d p h ysical  help, a n d was us ually  c o ntine nt  
0 ☐ nee de d p h ysical  help, a n d was us ually  inc o ntine nt  
4. 
Re gar di ng bat hi ng ,  i n t he past 4 w ee ks, w hi c h best des cri bes his/ her us ual  
pe rf or ma nce : 
3 ☐ bat he d wit h o ut  re min din g  or p h ysical  help  
2 ☐ n o p h ysical  help, b ut nee de d s u per visio n/re min ders  t o bat he c o m pletely  
1 ☐ nee de d min or p h ysical  help (e. g., wit h was hin g  hair) t o bat he c o m pletely  
0 ☐ nee de d t o be bat he d c o m pletely  
5. 
Re gar di ng gr o o mi ng ,  i n t he past 4 w ee ks, w hi c h best des cri bes his/ her o pti mal  
pe rf or ma nce : 
3 ☐ clea ne d a n d c ut fin ger nails  wit h o ut  p h ysical  help  
2 ☐ br us he d or c o m be d hair wit h o ut p h ysical  help  
1 ☐ ke pt face a n d ha n ds clea n wit h o ut  p h ysical  help  
0 ☐ nee de d help f or gr o o min g  of hair, face, ha n ds, a n d fin ger nails  
6a. 
Re gar di ng dre ssi ng , i n t he past 4 w ee ks, w hi c h best des cri bes his/ her us ual 
pe rf or ma nce  w he n s ele cti ng his/ he r first s et of cl ot hes f or t he da y: 
3 ☐ wit h o ut s u per visio n  or help  
2 ☐ wit h s u per visio n  
1 ☐ wit h p h ysical  help  
0 ☐ did n ot select his/ her clot hes  f or t he da y  
0 ☐ d o n’t k n o w  


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6 b. 
Re gar di ng p hysic all y  getti ng dress e d , w hi c h best des cri bes his/ her us ual 
pe rf or ma nce  i n t he past 4 w ee ks: 
4 ☐ dresse d c o m pletely  wit h o ut  s u per visio n  or p h ysical  help  
3 ☐ dresse d c o m pletely  wit h s u per visio n,  b ut wit h o ut  help  
2 ☐ nee de d p h ysical  help o nly f or b utt o ns, clas ps, or s h oelaces  
1 ☐ dresse d wit h o ut  help if clot hes nee de d n o faste nin g  or b utt o nin g  
0 ☐ al wa ys nee de d help, re gar dless  of t he t y pe of clot hin g 
0 ☐ d o n’t k n o w  
7. 
Re gar di ng t e le p ho ne  us a ge i n t he past 4 w ee ks, w hi c h best des cri bes his/ her 
hi g hest le vel of pe rf or ma nce : 
5 ☐ ma de calls  after lo o kin g  u p n u m bers in w hite or yello w  pa ges, or b y dialin g 
direct or y  assista nce  
4 ☐ ma de calls o nly t o well-k n o w n  n u m bers, wit h o ut referrin g  t o a direct or y  or list 
3 ☐ ma de calls  o nly t o well -k n o w n  n u m bers, b y usin g  a direct or y ,  list, or pre -
pr o gra m me d  n u m bers   
2 ☐ a ns were d t he p h o ne; did n ot ma ke calls  
1 ☐ did n ot a ns wer t he p h o ne, b ut s p o ke w he n p ut o n t he line  
0 ☐ did n ot use t he p h o ne  
0 ☐ d o n’t k n o w  
8. 
D uri ng   t he past 4 w ee ks, di d { P} w atc h t ele visi o n? 
☐ yes 
☐ n o 
☐ d o n’t k n o w  
 
If yes, as k all q uesti o ns: 
a. Di d { P }  us uall y s el ect or as k f or differ e nt pr o gr a ms or his/ her fa v orite s ho w ?  
1 ☐ yes 
0 ☐ n o  
0 ☐ d o n’t k n o w  
b.  Di d { P }  us uall y  tal k  a b o ut t he  c o nte nt  of a pr o gr a m  w hil e w atc hi ng  it?  
1 ☐ yes 
0 ☐ n o  
0 ☐ d o n’t k n o w  
c. Di d { P }  tal k a b o ut  t he c o nte nt  of a pr o gr a m  wit hi n  a da y ( 2 4 ho urs) after 
w atc hi ng  it?  
1 ☐ yes 
0 ☐ n o  
0 ☐ d o n’t k n o w  


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9. 
D uri ng   t he past 4 w ee ks, di d { P} e ver a p pear t o pa y atte nti o n  t o c o nve rs ati o n or 
s mall  t al k f or at l east 5 mi nutes,  whi c h best des cri bes his/ her us ual  de gre e  of 
partici pati o n : 
 
N ot e : { P} di d not nee d t o i niti ate t he c o nvers ati o n.  
3 ☐ us ually  said t hin gs  t hat were relate d t o t he t o pic  
2 ☐ us ually  said t hin gs  t hat were n ot relate d t o t he t o pic 
1 ☐ rarely or ne ver s p o ke 
0 ☐ did n ot participate  in c o n versatio ns  or s mall  talk  
0 ☐ d o n’t k n o w  
1 0. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes ho w { P } us uall y  cle are d dis he s 
f r o m t he t a ble after a meal or s nac k:  
3 ☐ wit h o ut s u per visio n  or help  
2 ☐ wit h s u per visio n  
1 ☐ wit h p h ysical  help  
0 ☐ did n ot clear dis hes  
0 ☐ d o n’t k n o w  
1 1. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes ho w { P } us uall y  ma na ge d  t o fi n d 
his/ he r  pe rs o nal  be l o ngi ngs  at ho me:  
3 ☐ wit h o ut s u per visio n  or help  
2 ☐ wit h s u per visio n  
1 ☐ wit h p h ysical  help  
0 ☐ did n ot fin d pers o nal belo n gin gs  
0 ☐ d o n’t k n o w  
1 2. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes { P }’s hi g hest le vel of pe rf or ma nce  
w he n o bt ai ni ng  a hot or c ol d be ve r a ge  f or hi m/ hers elf: 
3 ☐ ma de a h ot be vera ge, us ually  wit h o ut  p h ysical  help  
2 ☐ ma de a h ot be vera ge, us ually  if s o me o ne else heate d t he water  
1 ☐ o btaine d a c old be vera ge, us ually  wit h o ut  p h ysical  help  
0 ☐ did n ot o btain a be vera ge f or hi m/ herself  
0 ☐ d o n’t k n o w  
1 3. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes { P }’s hi g hest le vel of pe rf or ma nce  
w he n ma ki ng  hi m/ he rs elf a me al or s nac k at ho me:  
4 ☐ c o o ke d or micr o wa ve d  f o o d, wit h little  or n o help  
3 ☐ c o o ke d or micr o wa ve d  f o o d, wit h e xte nsive  help  
2 ☐ mixe d  or c o m bine d  f o o d ite ms f or a meal or s nac k, wit h o ut c o o kin g  or 
micr o wa vin g  (e. g., ma de a sa n d wic h }  
1 ☐ o btaine d f o o d o n his/ her  o w n, wit h o ut mixin g  or c o o kin g  it  
0 ☐ did n ot ma ke hi m/ herself  a meal or s nac k  
0 ☐ d o n’t k n o w  


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1 4. 
D uri ng  t he past 4  w ee ks, w hi c h best des cri bes ho w { P } us uall y  dis pos e d  of 
g ar ba ge or litt e r  i n t he a p pr o pri ate pl ace or c o ntai ner at ho me: 
3 ☐ wit h o ut s u per visio n  or help  
2 ☐ wit h s u per visio n  
1 ☐ wit h p h ysical  help  
0 ☐ did n ot dis p ose of gar ba ge  or litter  in a n a p pr o priate  place  or c o ntainer  
0 ☐ d o n’t k n o w  
1 5. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes { P }’s o pti mal  pe rf or ma nce  w he n 
getti ng ar o u n d  ( or t r a veli ng) o utsi de of his/ he r ho me : 
4 ☐ alo ne, we nt at least 1  mile  a wa y fr o m h o me  
3 ☐ alo ne, b ut re maine d wit hin  1 mile  of h o me  
2 ☐ o nly w he n acc o m pa nie d  a n d s u per vise d,  re gar dless  of t he trip  
1 ☐ o nly wit h p h ysical  help, re gar dless  of t he trip  
0 ☐ did n ot get ar o u n d ( or tra vel) o utside  of his/ her h o me  
0 ☐ d o n’t k n o w  
1 6a. O n s ho p pi ng  t ri ps d uri ng t he past 4 w ee ks, w hi c h best des cri bes ho w { P } us uall y 
s ele ct e d it e ms: 
3 ☐ wit h out s u per visio n  or p h ysical  help  
2 ☐ wit h s o me s u per visio n  or p h ysical  help  
1 ☐ n ot at all,  or selecte d mainly  ra n d o m or ina p pr o priate  ite ms 
0 ☐ did n ot go s h o p pin g  
0 ☐ d o n’t k n o w  
1 6 b. O n s ho p pi ng  t ri ps d uri ng t he past 4 w ee ks, di d { P } us uall y  pa y f or it e ms wit ho ut 
s u pe r visi o n  or  p hysic al  he l p? 
1 ☐ yes 
0 ☐ n o 
0 ☐ did n ot go s h o p pin g  
0 ☐ d o n’t k n o w  
1 7. 
D uri ng  t he past 4 w ee ks, w he n  kee pi ng  a p p oi nt me nts  or meeti ngs  wit h ot her pe o pl e 
s uc h as r el ati ves, a d oct or, t he hair dr ess er, etc., w hi c h best des cri bes { P }’s 
a w are ness of t he a p poi nt me nt  or me eti ng a he a d of ti me : 
3 ☐ us ually  re me m bere d, ma y ha ve nee de d  writte n re min ders  e. g. n otes, a diar y, or 
cale n dar  
2 ☐ o nly re me m bere d t he a p p oint me nt  after ver bal  re min ders  o n t he da y  
1 ☐ us ually  did n ot re me m ber, in s pite  of ver bal  re min ders  o n t he da y  
0 ☐ did n ot kee p a n y a p p oint me nts  or meetin gs  
0 ☐ d o n’t k n o w  


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1 8. 
D uri ng  t he past 4 w ee ks, w as { P } e ve r left o n his/ he r o w n? 
N ot e: Bei n g t ake n t o d ay c ar e or h avi n g a sitt er at h o me d oes n ot c o nstit ut e bei n g 
l eft al o ne. 
☐ yes 
☐ n o 
☐ d o n’t k n o w  
☐ n ot a p plica ble – { P } is instit utio naliz e d  
If yes, as k all  q ue sti o ns:  
a. Was { P } l eft a w a y fr o m  ho me,  f or 1 5 mi nutes  or l o nger, d uri ng  t he  da y?  
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
b. Was { P] l eft at ho me,  f or a n ho ur or l o nger, d uri ng  t he  da y?  
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
c. Was { P] l eft at ho me, f or l ess t ha n  1 ho ur,  d uri ng  t he da y? 
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
1 9.  
D uri ng t he past 4 w ee ks, di d { P} t al k a bo ut  c urre nt  e ve nts? 
N ot e:  T his me a ns eve nts or i nci de nts t h at occ urr e d d uri n g t he p ast m o nt h.  
☐ yes 
☐ n o 
☐ d o n’t k n o w  
 
If yes, as k all q ue sti o ns:  
a. Di d { P } tal k a b o ut  e ve nts t hat:  he/s he  hear d or r ea d a b o ut or s a w o n T V b ut di d 
not  ta ke part i n?  
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
b. Di d { P } tal k a b o ut  e ve nts t hat:  he/s he t o o k  part i n o utsi de ho me i nv ol vi ng 
fa mil y, fri e nds, or nei ghb ors ? 
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  


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c 
Di d { P } tal k a b o ut  e ve nts t hat:  occ urr e d at  ho me  t hat  he/s he t o o k  part i n or 
w atc he d?  
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
2 0a. Di d { P }  us uall y t al k a bo ut det ails of w hat he/s he re a d w hile or s hortl y (less 
t ha n  1 ho ur) aft e r re a di ng ? 
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
2 0 b. Di d { P } us uall y t al k a bo ut w hat he/s he re a d 1 ho ur  or l o nge r aft e r re a di ng? 
1 ☐ yes 
0 ☐ n o 
0 ☐ d o n’t k n o w  
2 1. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes t he most  c o m plic at e d  t hi ngs  t hat 
{ P} wr ot e do w n : 
3 ☐ letters or lo n g  n otes t hat ot her pe o ple u n derst o o d 
2 ☐ s h ort n otes or messa ges  t hat ot her pe o ple  u n derst o o d 
1 ☐ his/ her signat ure  or na me  
0 ☐ did n ot write t hin gs  d o w n  
0 ☐ d o n’t k n o w  
2 2. 
D uri ng  t he past 4 w ee ks, w hi c h best des cri bes ho w { P } us uall y  pe rf or me d his/ her  
most c o m mo n  pasti me, ho b by,  or g a me : 
N ot e:  W al ki n g d oes n ot c o u nt as a p asti me/ h o b by f or t his s c al e.  Ex a m pl es i ncl u de 
c ar d or b o ar d g a mes (i ncl u di n g bri d ge, c hess, c heckers), bi n g o, cr oss w or ds, 
art, m usi c al i nstr u me nt, k nitti n g, s e wi n g, r e a di n g, g ar de ni n g, g olf, t e n nis, 
w or ks h o p, fis hi n g.  
3  ☐ wit h o ut s u per visio n  or help  
2 ☐ wit h s u per visio n  
1 ☐ wit h p h ysical help  
0 ☐ did n ot perf or m a n y pasti mes,  h o b bies, or ga mes  
0 ☐ d o n’t k n o w  
If { P} pe rf or me d ho b bies/ pasti mes,  we re t he y pe rf or me d  o nl y at da y c are ? 
☐ yes 
☐ n o 
2 3. 
Re gar di ng  t he us e of a ho us e hol d  a p pli a nce   t o do  c hore s d uri ng  t he past 4 w ee ks, 
w hi c h best des cri bes ho w { P } us uall y  us e d  t he  most  c o m mo n  a p pli a nce s : 
N ot e:  T his d oes n ot i ncl u de a T V.   Ex a m pl es i ncl u de w as her, dr yer, v ac u u m, 
dis h w as her, t o ast er, t o ast er ove n, r a n ge, mi cr o w ave, f o o d pr ocess or.  
4 ☐ wit h o ut help, o peratin g  m ore t ha n o n -off c o ntr ols  if nee de d  


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3 ☐ wit h o ut help, b ut o perate d o nly o n/ off c o ntr ols  
2 ☐ wit h s u per visio n,  b ut n o p h ysical  help  
1 ☐ wit h p h ysical  help  
0 ☐ did n ot use a h o use h old  a p plia nce  t o d o c h ores  
0 ☐ d o n’t k n o w  
 
T ot al Sc ore ( 0 -7 8): _ _ _  
N u m be r  of " D o n't  K no w "  Re s po ns e s: _ _ _  
 
 
 


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A P P E N DI X 5: 
N E U R O P S Y C HI A T RI C  I N V E N T O R Y   1 2-I T E M 
A. D E L U SI O N S  ( N A)  
D oes t he pati e nt ha ve beli efs t hat yo u kno w ar e not tr ue (f or e xa mpl e, i nsisti ng t hat 
pe o pl e ar e tr yi ng t o har m hi m/ her or steal fr o m hi m/ her) ? Has he/s he s ai d t hat fa mil y 
me mbers ar e not w ho t he y s a y t he y ar e or t hat t he ho us e is not t heir ho me?  I’ m  not 
as ki ng a b o ut mer e s us pi ci o us ness; I a m i nter este d if t he pati e nt is c o nvi nce d t hat t hes e 
t hi ngs  ar e ha p pe ni ng  t o hi m/ her. 
 
 Y es (If yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  belie ve  t hat he/s he is in da n ger ‐ t hat ot hers are pla n nin g  t o h urt hi m/ her? 
 Yes  N o 
2. 
D oes t he patie nt  belie ve  t hat ot hers are stealin g  fr o m hi m/ her?  
 Yes  N o 
3. 
D oes t he patie nt  belie ve  t hat his/ her  s p o use is ha vin g  a n affair? 
 Yes  N o 
4. 
D oes t he patie nt  belie ve  t hat u n welc o me  guests  are livin g  in his/ her h o use?  
 Yes  N o 
5. 
D oes t he patie nt  belie ve  t hat his/ her  s p o use or ot hers are n ot w h o t he y clai m  t o be?  
 Yes  N o 
6. 
D oes t he patie nt  belie ve  t hat his/ her  h o use i s n ot his/ her h o me?  
 Yes  N o 
7. 
D oes t he patie nt  belie ve  t hat fa mily  me m bers pla n  t o a ba n d o n hi m/ her?  
 Yes  N o 
8. 
D oes t he patie nt  belie ve  t hat tele visio n  or ma gazine  figures  are act ually  prese nt in t he 
h o me? ( D oes he/s he tr y t o talk or interact wit h t he m?) 
 Yes  N o 
9.  
D oes t he patie nt  belie ve  a n y ot her u n us ual  t hin gs  t hat I ha ve n’t as ke d a b o ut?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he delusio ns. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k 
 
 2. S o meti mes – a b o ut o nc e per we e k 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y 
 
 4. Ver y ofte n – o nc e or m or e per da y  
Se verit y: 
 
 1. Mil d – del usi o ns pr es e nt b ut s e e m har ml ess a n d pr o d uc e littl e distr ess i n t he pati e nt.  
 
 2. M o der at e – del usi o ns ar e distr essi n g a n d disr u pti ve.  
 
 3. Se ver e – del usi o ns ar e ver y disr u pti ve a n d ar e a maj or s o ur c e of be ha vi or al disr u pti o n. (If P R N  
 
me di c ati o ns ar e pr es cri be d, t heir us e si g nals t hat t he del usi o ns ar e of mar ke d  
 
s e verit y.) 


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Distres s:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r? 
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
  5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
 r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es)  
 
B. H A L L U CI N A T I O N S  ( N A) 
D oes t he pati e nt ha ve hall uci nati o ns s uc h as s eei ng fals e visi o ns or heari ng fals e v oi ces ? 
D oes he/s he s ee m t o s ee, hear or e xperi e nce t hi ngs  t hat ar e not pr es e nt? B y t his q uesti o n 
w e d o not  mea n  j ust  mista ke n  beli efs s uc h as stati ng t hat s o me o ne w ho has di e d is still 
ali ve; r at her w e ar e as ki ng if t he pati e nt act uall y has a b nor mal e xperi e nces of s o unds or 
visi o ns. 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scre nin g  q uestio n)  
 N/ A 
 
1. 
D oes t he patie nt  describe hearin g  v oices or  act as if he/s he hears v oices?  
 Yes  N o 
2. 
D oes t he patie nt  talk t o pe o ple w h o are n ot t here?  
 Yes  N o 
3. 
D oes he/s he describe seein g  t hin gs  n ot see n b y ot hers or be ha ve as if he/s he is seein g 
t hin gs  n ot see n b y ot hers ( pe o ple, a ni mals,  lights, etc. )? 
 Yes  N o 
4. 
D oes he/s he re p ort s mellin g  o d ors n ot s melle d  b y ot hers?  
 Yes  N o 
5. 
D oes he/s he describe feel in g  t hin gs  o n his/ her s kin  or ot her wise  a p pear t o be feelin g  t hin gs 
cra wlin g  or t o uc hin g  hi m/ her?  
 Yes  N o 
6. 
D oes he/s he describe tastes t h at are wit h o ut a n y k n o w n ca use?  
 Yes  N o 
7. 
D oes he/s he describe a n y ot h er u n us ual se ns or y e xperie nces?  
 Yes  N o  
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he hallucinatio ns. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – o nc e or m or e per da y.  
Se verit y: 
 
 1. Mil d – hall uci nati o ns ar e pr es e nt b ut har ml ess a n d c a us e littl e distr ess f or t he pati e nt.  
 
 2. M o der ate – hall uci nati o ns ar e distr essi n g a n d ar e disr u pti ve t o t he pati e nt.  


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 3. Se ver e – hall uci nati o ns ar e ver y disr u pti ve a n d  ar e a maj or s o ur c e of be ha vi or al dist ur ba nc e.  
 
P R N me di c ati o ns ma y be r e q uir e d t o c o ntr ol t he m.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
  5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or st aff a n d ot her  
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
C. A GI T A TI O N/ A G G R E S SI O N  ( N A)  
D oes t he pati e nt ha ve peri o ds w he n he/s he r ef us es t o c o o per ate or w o n’t l et pe o pl e hel p 
hi m/ her ?  Is he/s he  har d t o ha ndl e?  
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  get u pset wit h t h ose tr yin g  t o care f or hi m/ her or resi st activities  s uc h as 
bat hin g  or c ha n gin g  clot hes?  
 Yes  N o 
2. 
Is t he patie nt st u b b or n, ha vin g  t o ha ve t hin gs  his/ her  wa y? 
 Yes  N o 
3. 
Is t he patie nt u nc o o perative, resistive  t o help fr o m ot hers? 
 Yes  N o 
4. 
D oes t he patie nt  ha ve a n y ot her be ha viors  t hat ma ke hi m/ her  har d t o ha n dle?  
 Yes  N o 
5. 
D oes t he patie nt  s h o ut or c urse a n grily?  
 Yes  N o 
6. 
D oes t he patie nt  sla m d o ors, kic k f ur nit ure, t hr o w t hin gs?  
 Yes  N o 
7. 
D oes t he patie nt  atte m pt t o h urt or hit ot hers?  
 Yes  N o 
8.  
D oes t he patie nt  ha ve a n y ot her a ggressive  or a gitate d  be ha viors?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he 
a gitatio n/a g gressio n. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – o nc e or m or e per da y.  
Se verit y: 
 
 1. Mil d – a git ati o n is disr u pti ve b ut c a n be ma na ge d wit h r e dir e cti o n or r e ass ur a nc e.  


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 2. M o der ate – a gi t ati o n is disr u pti ve a n d diffi c ult t o r e dir e ct or c o ntr ol. 
 
 3. Se ver e – a git ati o n is ver y disr u pti ve a n d a maj or s o ur c e of diffi c ult y; t her e ma y be a t hr e at of  
pers o nal har m. Me di c ati o ns ar e oft e n r e q uir e d.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o st aff a n d ot her r esi de nts, maj or ti me i nfri n ge me nt)  
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
D. D E P R E S SI O N/ D Y S P H O RI A  ( N A)  
D oes t he pati e nt s ee m s a d or de pr ess e d? D oes he/s he s a y t hat he/s he feels s a d or 
de pr ess e d? 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  ha ve perio ds of tearf ulness  or s o b bin g  t hat see m t o in dicate  sa d ness? 
 Yes  N o 
2. 
D oes t he patie nt  sa y, or act as if, he/s he is sa d or in lo w s pirits?  
 Yes  N o 
3. 
D oes t he patie nt  p ut hi m/ herself  d o w n or sa y t hat he/s he feels  like  a failure?  
 Yes  N o  
4. 
D oes t he patie nt  sa y t hat he/s he is a ba d pers o n or deser ves t o be p u nis he d?  
 Yes  N o 
5. 
D oes t he patie nt  see m ver y disc o ura ge d  or sa y t hat he/s he has n o f ut ure?  
 Yes  N o 
6. 
D oes t he patie nt  sa y he/s he is a b ur de n t o t he fa mily  or t hat t he fa mily  w o uld be better off 
wit h o ut  hi m/ her?  
 Yes  N o 
7. 
D oes t he patie nt  e xpress a wis h f or deat h or talk a b o ut killin g  hi mself/ herself?  
 Yes  N o 
8. 
D oes t he patie nt  s h o w a n y ot her signs  of de pressio n  or sa d ness?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he 
de pressio n/ d ys p h oria. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y oft e n – ess e nti all y c o nti n u o usl y pr es e nt. 


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Se verit y: 
 
 1. Mil d – de pr essi o n is distr essi n g b ut us uall y r es p o n ds t o r e dir e cti o n or r e ass ur a nc e.  
 
 2. M o der ate – de pr essi o n is distr essi n g; de pr essi ve s y m pt o ms ar e s p o nt a ne o usl y voi c e d b y t he  
pati e nt a n d  diffi c ult t o all e vi at e.  
 
 3. Se ver e – de pr essi o n is ver y distr essi n g a n d a maj or s o ur c e of s uff eri n g f or t he pati e nt.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge i n wor k r o uti ne b ut littl e ti me r e b u d geti n g r e q uir e d)  
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or st aff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
E. A N XI E T Y  ( N A)  
Is t he pati e nt ver y ner v o us, w orri e d, or fri ghte ne d  f or no a p par e nt r eas o n? D oes he/s he 
s ee m ver y te ns e or fi d get y?  Is t he pati e nt afr ai d t o be a part fr o m yo u? 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  sa y t hat he/s he i s w orrie d  a b o ut pla n ne d e vents? 
 Yes  N o 
2. 
D oes t he patie nt  ha ve perio ds of feelin g  s ha k y, u na ble t o rela x,  or feelin g  e xcessively 
te nse?  
 Yes  N o 
3. 
D oes t he patie nt  ha ve perio ds of [ or c o m plain  of] s h ort ness of breat h, gas pin g,  or sighin g 
f or n o a p pare nt reas o n ot her t ha n ner v o us ness?   
 Yes  N o 
4. 
D oes t he patie nt  c o m plain  of b utterflies  in his/ her st o mac h, or of racin g  or p o u n din g  of t he 
heart in ass ociatio n  wit h ner v o us ness?  ( S y m pt o ms n ot e xplaine d  b y ill  healt h)  
 Yes  N o 
5. 
D oes t he patie nt  a v oid certain places  or sit uatio ns  t hat ma ke hi m/ her m ore ner v o us s uc h as 
ridin g  in t he car, meetin g  wit h frie n ds,  or bein g  in cr o w ds?  
 Yes  N o 
6. 
D oes t he patie nt  bec o me ner v o us a n d u pset w he n se parate d fr o m y o u ( or his/ her 
care giver)?  ( D oes he/s he clin g  t o y o u t o kee p fr o m bein g  se parate d?)  
 Yes  N o 
7. 
D oes t he patie nt  s h o w a n y ot her signs  of a n xiet y?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he a n xiet y. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 


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 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – o nc e or m or e per da y.  
Se verit y: 
 
 1. Mil d – a n xi et y is distr essi n g b ut us uall y r es p o n ds t o r e dir e cti o n or r e ass ura nc e.  
 
 2. M o der at e – a n xi et y is distr essi n g, a n xi et y s y m pt o ms ar e s p o nt a ne o usl y voi c e d b y t he pati e nt 
a n d diffi c ult t o all e vi at e. 
 
 3. Se ver e – a n xi et y is ver y distr essi n g a n d a maj or s o ur c e of s uff eri n g f or t he pati e nt.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver ely ( disr u pti ve, u ps etti n g t o st aff a n d ot her r esi de nts, maj or ti me i nfri n ge me nt)  
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
F.  E L A TI O N/ E U P H O RI A  ( N A)  
D oes t he pati e nt s ee m t o o c heerf ul or t o o ha p p y f or no r eas o n? I d o n’t mea n  t he nor mal 
ha p pi ness t hat c o mes fr o m s eei ng fri e nds, r ecei vi ng pr es e nts, or s pe ndi ng ti me wit h 
fa mil y me mbers. I a m as ki ng if t he pati e nt has a persiste nt a nd a b nor mall y go o d mo o d or 
fi nds hu mor  w her e ot hers d o not. 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  a p pear t o feel t o o go o d or t o be t o o ha p p y, differe nt fr o m his/ her u s ual 
self?  
 Yes  N o 
2. 
D oes t he patie nt  fin d h u m or a n d la u gh  at t hin gs  t hat ot hers d o n ot fin d f u n n y?  
 Yes  N o 
3. 
D oes t he patie nt  see m t o ha ve a c hildis h  se nse of h u m or wit h a te n de nc y t o giggle  or  la u gh 
ina p pr o priately  (s uc h as w he n s o met hin g  u nf ort u nate ha p pe ns t o ot hers)?  
 Yes  N o 
4. 
D oes t he patie nt  tell  j o kes or ma ke re mar ks t hat are n ot f u n n y t o ot hers b ut see m f u n n y t o 
hi m/ her?   
 Yes  N o 
5. 
D oes he/s he pla y c hildis h  pra n ks s uc h as pinc hin g  or pla yin g  “ kee p a wa y” f or t he f u n of it?  
 Yes  N o 
6. 
D oes t he patie nt  “talk big”  or clai m  t o ha ve m ore a bilities  or wealt h t ha n is tr ue?  
 Yes  N o 
7. 
D oes t he patie nt  s h o w a n y ot her signs  of feelin g  t o o go o d or bein g  t o o ha p p y?  
 Yes  N o 


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If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he 
elatio n/e u p h oria. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – ess e nti all y c o nti n u o usl y pr es e nt. 
Se verit y: 
 
 1. Mil d – el ati o n is n ot a bl e t o fri e n ds a n d f a mil y b ut is n ot disr u pti ve.  
 
 2. M o der ate – el ati o n is n ot a bl y a b n or mal. 
 
 3. Se ver e – el ati o n is ver y pr o n o u nc e d; pati e nt is e u p h ori c a n d fi n ds ne arl y e ver yt hi n g t o be 
h u m or o us.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
G. A P A T H Y/I N DI F F E R E N C E  ( N A)  
Has t he  pati e nt l ost i nter est i n t he  w orl d ar o und  hi m/ her ?  Has he/s he l ost i nter est i n d oi ng 
t hi ngs  or d oes he/s he l ac k moti vati o n f or starti ng ne w acti viti es ? Is he/s he mor e diffi c ult 
t o e nga ge  i n c o nversati o n or i n d oi ng c hor es ? Is t he pati e nt a pat heti c or i ndiffer e nt?  
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1.  
D oes t he patie nt  see m less s p o nta ne o us a n d less active  t ha n us ual?  
 Yes  N o 
2.  
Is t he patie nt less likely  t o initiate  a c o n versatio n?  
 Yes  N o 
3.  
Is t he patie nt less affectio nate  or lac kin g  in e m otio ns w he n c o m pare d t o his/ her  us ual self?  
 Yes  N o 
4.  
D oes t he patie nt  c o ntrib ute  less t o h o use h old  c h ores?  
 Yes  N o 
5.  
D oes t he patie nt  see m less intereste d  in t he activities  a n d pla ns  of ot hers?  
 Yes  N o 
6.  
Has t he patie nt  lost interest in frie n ds a n d fa mily  me m bers?  
 Yes  N o 
7.  
Is t he patie nt less e nt h usiastic  a b o ut his/ her us ual interests? 
 
 
Ye s 
 N o
 


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8.   
D o es t he patie nt  s h o w a n y ot her signs  t hat he/s he d oes n’t care a b o ut d oin g  ne w t hin gs?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he 
a pat h y/in differe nce. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – ne arl y al wa ys pr es e nt.  
Se verit y: 
 
 1. Mil d – a pat h y is n ot a bl e b ut pr o d uc es littl e i nt erfere nc e wit h dail y r o uti nes; o nl y mil dl y 
diff er e nt  fr o m pati e nt’s us ual be ha vi or; pati e nt r es p o n ds t o s u g gesti o ns t o e n ga ge i n acti viti es. 
 
 2. M o der ate – a pat h y is ver y e vi de nt; ma y be o ver c o me b y t he c ar e gi ver wit h c o a xi n g a n d 
e nc o ur a ge me nt; r es p o n ds s p o nt a ne o usl y o nl y t o p o werf ul e ve nts s uc h as visits  fr o m cl os e r el ati ves 
or f a mil y me m bers.  
 
 3. Se ver e – a pat h y is ver y e vi de nt a n d us uall y f ails t o r es p o n d t o a n y e nc o ur a ge me nt or e xt er nal 
e ve nts. 
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost no c ha n ge i n wor k r o uti ne)  
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
H. DI SI N HI BI TI O N  ( N A)  
D oes t he pati e nt s ee m t o act i mp ulsi vel y wit ho ut  t hi nki ng?  D oes he/s he d o or s a y t hi ngs 
t hat ar e not us uall y d o ne or s ai d i n p ubli c? D oes he/s he d o t hi ngs  t hat ar e e mbarr assi ng t o 
yo u  or ot hers ?  
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  act i m p ulsively  wit h o ut a p pearin g  t o c o nsider  t he c o nse q ue nces?  
 Yes  N o 
2.  
D oes t he patie nt  talk t o t otal stra n gers as if he/s he k ne w t he m?  
 Yes  N o 
3.  
D oes t he patie nt  sa y t hin gs  t o pe o ple t hat are inse nsitive  or h urt t heir feelin gs?  
 Yes  N o 
4.  
D oes t he patie nt  sa y cr u de t hin gs  or ma ke se xual  re mar ks t hat he/s he w o uld n ot us ually 
ha ve said?  
 Yes  N o 


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5.  
D oes t he patie nt  talk o pe nly a b o ut ver y pers o nal or private  matters n ot us ually  disc usse d in 
p u blic?   
 Yes  N o 
6.  
D oes t he patie nt  ta ke liberties  or t o uc h or h u g ot hers in wa y t hat is o ut of c haracter f or 
hi m/ her?   
 Yes  N o 
7.  
D oes t he patie nt  s h o w a n y ot her signs  of loss of c o ntr ol  of his/ her i m p ulses?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he disin hibitio n. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – ess e nti all y c o nti n u o usl y pr es e nt. 
Se verit y: 
 
 1. Mil d – disi n hi biti o n is n ot a bl e b ut us uall y r es p o n ds t o r e dir e cti o n a n d g ui da nc e.  
 
 2. M o der ate – disi n hi biti o n is ver y e vi de nt a n d diffi c ult t o o ver c o me b y t he c ar e gi ver.  
 
 3. Se ver e – disi n hi biti o n us uall y f ails t o r es p o n d t o a n y  i nt er ve nti o n b y t he c ar e gi ver, a n d is a 
s o ur c e of e m barr ass me nt or s o ci al distress. 
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  in wor k r o uti ne b ut littl e ti me r e b u d geti n g r e q uir e d)  
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or st aff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
I. I R RI T A BI LI T Y/ L A BI LI T Y  ( N A) 
D oes t he pati e nt get irritate d a nd easil y dist ur be d? Ar e his/ her mo o ds ve r y c ha ngea bl e? Is 
he/s he a b nor mall y i mpati e nt? We d o not mea n fr ustr ati o n o ver me mor y  l oss or i na bilit y 
t o perf or m us ual tas ks; w e ar e i nter este d t o kno w if t he pati e nt has a b nor mal irrita bilit y, 
i mpati e nce, or r a pi d e moti o nal c ha nges  differ e nt fr o m his/ her us ual s elf. 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1. 
D oes t he patie nt  ha ve a ba d te m per,  “flyin g  off t he ha n dle”  easily  o ver little  t hin gs?  
 Yes  N o 
2. 
D oes t he patie nt  ra pidly  c ha n ge  m o o ds fr o m o ne t o a n ot her, bein g  fine o ne min ute a n d 
a n gr y t he ne xt?  
 Yes  N o 
3.  
D oes t he patie nt  ha ve s u d de n flas hes  of a n ger?  
 Yes  N o 


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4.  
Is t he patie nt i m patie nt,  ha vin g  tr o u ble  c o pin g  wit h dela ys  or waitin g  f or pla n ne d 
activities?   
 Yes  N o 
5.  
Is t he patie nt cra n k y a n d irrita ble?  
 Yes  N o 
6.  
Is t he patie nt ar gu me ntative  a n d diffic ult  t o get alo n g  wit h?  
 Yes  N o 
7.  
D oes t he patie nt  s h o w a n y ot her signs  of irrita bilit y?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he 
irrita bilit y/la bilit y. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y oft e n – ess e nti all y c o nti n u o usl y pr es e nt. 
Se verit y: 
 
 1. Mil d – irrit a bilit y or l a bilit y is n ot a bl e b ut us uall y r es p o n ds t o r e dir e cti o n a n d r e ass ur a nc e. 
 
 2. M o der ate – irrit a bilit y a n d l a bilit y ar e ver y e vi de nt a n d diffi c ult t o o ver c o me b y t he c ar e gi ver.  
 
 3. Se ver e – irrit a bilit y a n d l a bilit y ar e ver y e vi de nt; t he y us uall y f ail t o r es p o n d t o a n y 
i nt er ve nti o n b y t he c ar e gi ver, a n d  t he y ar e a maj or s o ur c e of distr ess. 
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti ng)  
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es)  
 
J. A B E R R A N T  M O T O R B E H A VI O R  ( N A)  
D oes t he pati e nt pace, d o t hi ngs o ver a nd o ver s uc h as o pe ni ng cl os ets or dr a w ers, or 
r e peate dl y pi c k at t hi ngs  or wi nd stri ng or t hr ea ds ? 
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr oce d t o ne xt scree nin g  q uestio n)  
 N/ A 
 
1.  
D oes t he patie nt  pace ar o u n d t he h o use wit h o ut a p pare nt p ur p ose?  
 Yes  N o 
2.  
D oes t he patie nt  r u m ma ge ar o u n d o pe nin g  a n d u n pac kin g  dra wers or closets?  
 Yes  N o 
3.  
D oes t he patie nt  re peate dly  p ut o n a n d ta ke  off clot hin g?  
 Yes  N o 


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4.  
D oes t he patie nt  ha ve re petitive  activities  or “ ha bits”  t hat he/s he perf or ms o ver a n d o ver?  
 Yes  N o 
5.  
D oes t he patie nt  e n ga ge  in re petitive  activities  s uc h as ha n dlin g  b utt o ns, pic kin g,  wra p pin g 
strin g, etc. ?  
 Yes  No 
6.  
D oes t he patie nt  fid get  e xcessively,  see m u na ble t o sit still,  or b o u nce his/ her feet or ta p 
his/ her fin gers  a lot?  
 Yes  N o 
7.  
D oes t he patie nt  d o a n y ot her activities  o ver a n d o ver?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he a berra nt m ot or 
activit y: 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – ess e nti all y c o nti n u o usl y pr es e nt. 
Se verit y: 
 
 1. Mil d – a b n or mal m ot or acti vit y is n ot a bl e b ut pr o d uc es littl e i nt erf er e nc e wit h dail y r o uti nes.  
 
 2. M o der ate – a b n or mal m ot or acti vit y is ver y e vi de nt; c a n be o ver c o me b y t he c ar e gi ver.  
 
 3. Se ver e – a b n or mal m ot or acti vit y is ve r y e vi de nt, us uall y f ails t o r es p o n d t o a n y i nt er ve nti o n 
b y t he c ar e gi ver a n d  is a maj or s o ur c e of distr ess.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y (al m ost n o c ha n ge i n wor k r o uti ne b ut littl e ti me r e b u d geti n g r e q uir e d)  
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or Extr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or st aff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
K.  S L E E P A N D NI G H T TI M E  B E H A VI O R  DI S O R D E R S  ( N A)  
D oes t he pati e nt ha ve diffi c ult y sl ee pi ng ( d o not c o unt as pr es e nt if t he pati e nt si mpl y 
gets up o nce or t wi ce per ni ght  o nl y t o go t o t he bat hr o o m a nd falls bac k asl ee p 
i m me di atel y) ? Is he/s he up at ni ght?  D oes he/s he w a nder at ni ght,  get dr ess e d, or dist ur b 
yo ur  sl ee p?  
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 


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1.  
D oes t he patie nt  ha ve diffic ult y  fallin g  aslee p?  
 Yes  N o 
2.  
D oes t he patie nt  get u p d urin g  t he night  ( d o n ot c o u nt if t he patie nt  gets u p o nce or t wice 
per night  o nly t o go t o t he bat hr o o m a n d falls  bac k aslee p i m me diately)?  
 Yes  N o 
3.  
D oes t he patie nt  wa n der, pace, or get in v olve d  in ina p pr o priate  activities  at night?  
 Yes  N o 
4.  
D oes t he patie nt  a wa ke n y o u d urin g  t he night?  
 Yes  N o 
5.  
D oes t he patie nt  wa ke u p at night, dress, a n d pla n t o go o ut, t hin kin g  t hat it is m or nin g  a n d 
ti me t o start t he da y?  
 Yes  N o 
6.  
D oes t he patie nt  a wa ke n t o o early in t he m or nin g  (earlier  t ha n was his/ her ha bit)?  
 Yes  N o 
7.  
D oes t he patie nt  slee p e xcessively  d urin g  t he da y?  
 Yes  N o 
8.  
D oes t he patie nt  ha ve a n y ot her nightti me  be ha viors  t hat b ot her y o u t hat we ha ve n’t talke d  
a b o ut?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he nightti me 
be ha vior. 
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut less t ha n e ver y da y. 
 
 4. Ver y ofte n – o nc e or m or e per da y ( e ver y ni g ht).  
Se verit y: 
 
 1. Mil d – ni g htti me be ha vi ors o c c ur b ut t he y ar e n ot parti c ul arl y disr u pti ve.  
 
 2. M o der ate – ni g htti me be ha vi ors o c c ur a n d dist ur b t he pati e nt a n d t he sl e e p of t he c a r e gi ver; 
m or e  t ha n o ne t y pe of ni g htti me be ha vi or ma y be pr es e nt. 
 
 3. Se ver e – ni g htti me be ha vi ors o c c ur; s e ver al t y pes of ni g htti me be ha vi or ma y be pr es e nt; t he 
pati e nt is ver y distr ess e d d uri n g t he ni g ht a n d t he c ar e gi ver’s sl e e p is mar ke dl y dist ur be d.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o c ha n ge i n wor k r o uti ne) 
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 
 
 3. M o der atel y ( disr u pts wor k r o utine, r e q uir es ti me r e b u d geti n g)  
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o staff a n d  ot her r esi de nts, maj or ti me i nfri n ge me nt) 
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or st aff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 0 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
L. A P P E TI T E  A N D  E A TI N G C H A N G E S  ( N A)  
Has he/s he ha d a ny c ha nge i n a p petite, w ei ght, or eati ng ha bits ( c o unt  as N A if t he 
pati e nt is i nca pacitate d a nd has t o be fe d) ? Has t her e bee n a ny c ha nge i n t ype of f o o d 
he/s he pr efers ?  
 
 Y es (if yes, please  pr ocee d t o s u b q uestio ns) 
 N o (if n o, please  pr ocee d t o ne xt scree nin g  q uestio n) 
 N/ A 
 
1.  
Has he/s he ha d a loss of a p petite?  
 Yes  N o 
2.  
Has he/s he ha d a n increase  in a p petite?  
 Yes  N o 
3.  
Has he/s he ha d a loss of weight?  
 Yes  N o 
4.  
Has he/s he gaine d  weight?  
 Yes  N o 
5.  
Has he/s he ha d a c ha n ge  in eatin g  be ha vior  s uc h as p uttin g  t o o m uc h f o o d in his/ her  m o ut h 
at o nce?  
 Yes  N o 
6.  
Has he/s he ha d a c ha n ge  in t he kin d of f o o d he/s he likes  s uc h as eatin g  t o o ma n y s weets or 
ot her s pecific  t y pes of f o o d?  
 Yes  N o 
7.  
Has he/s he de velo pe d  eatin g  be ha viors  s uc h as eatin g  e xactly  t he sa me t y pes of f o o d eac h 
da y or eatin g  t he f o o d in e xactly  t he sa me or der?  
 Yes  N o 
8.  
Ha ve t here bee n a n y ot her c ha n ges  in a p petite  or eatin g  t hat I ha ve n’t as ke d a b o ut?  
 Yes  N o 
If t he scree nin g  q uestio n is c o nfir me d,  deter mine t he fre q ue nc y a n d se verit y  of t he c ha n ges in 
eatin g  ha bits  or a p petite.  
Fre q ue nc y:  
 
 1. Rar el y – l ess t ha n o nc e per we e k. 
 
 2. S o meti mes – a b o ut o nc e per we e k. 
 
 3. Ofte n – s e ver al ti mes per we e k b ut l ess t ha n e ver y da y. 
 
 4. Ver y ofte n – o nc e or m or e per da y or c o nti n u o usl y.  
Se verit y: 
 
 1. Mil d – c ha n ges i n a p petit e or e ati n g ar e pr es e nt b ut ha ve n ot l e d t o c ha n ges i n wei g ht a n d ar e 
n ot dist ur bi n g.  
 
 2. M o der ate – c ha n ges i n a p petit e or e ati n g ar e pr es e nt a n d c a us e mi n or fl uct uati o ns i n wei g ht.  
 
 3. Se ver e – o b vi o us c ha n ges i n a p petit e or e ati n g ar e pr es e nt a n d c a us e fl uct uati o ns i n wei g ht, ar e 
e m barr assi n g, or ot her wis e dist ur b t he pati e nt.  
Distress:  H o w e m oti o n all y distressi n g  d o y o u fi n d t his be h a vi o r?  
 
 0. N ot at all 
 
 1. Mi ni mall y ( al m ost n o cha n ge i n wor k r o uti ne)  
 
 2. Mil dl y ( al m ost n o c ha n ge  i n wor k r o uti ne b ut little ti me r e b u d geti n g r e q uir e d) 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 0 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
 
 3. M o der atel y ( disr u pts wor k r o uti ne, r e q uir es ti me r e b u d geti n g) 
 
 4. Se ver el y ( disr u pti ve, u ps etti n g t o st aff a n d ot her r esi de nts, maj or ti me i nfri n ge me nt)  
 
 5. Ver y Se ver el y or E xtr e mel y ( ver y disr u pti ve, maj or s o ur c e of distr ess f or staff a n d ot her 
r esi de nts, r e q uir es ti me us uall y de vot e d t o ot her r esi de nts or acti viti es) 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 0 8  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 6: 
C O R N E L L  S C A L E  F O R D E P R E S SI O N  A N D  D E M E N TI A 
Rati ngs  s ho ul d be bas e d o n s y mpt o ms  a nd si gns  occ urri ng  d uri ng  t he w ee k bef or e 
i nter vi e w. N o s c or e s ho ul d be gi ve n if s y mpt o ms  r es ult fr o m p hysi cal dis a bilit y or 
ill ness. 
I N S T R U C TI O N S 
1.  T he sa me rater s h o uld  c o n d uct t he inter vie w  eac h ti me  t o ass ure c o nsiste nc y  in t he res p o nse.  
2.  T he assess me nt s h o uld  be base d o n t he patie nt’s n or mal  wee kly r o utine.  
3.  If u ncertain  of a ns wers, q uestio nin g  ot her care givers  ma y f urt her define  t he ans wer. 
4.  Ans wer  all q uestio ns  b y placin g  a c hec k in t he c olu m n u n der t he a p pr o priately  n u m bere d 
a ns wer. (a = u na ble  t o e valuate, 0 =a bse nt, 1 = mild  t o inter mitte nt,  2 =se vere).  
5.  Ad d t he t otal sc ore f or all  n u m bers c hec ke d f or eac h q uestio n.  
6.  Place t he t otal sc ore in t he “ S C O R E” b o x a n d rec or d a n y s u bjective  o bser vatio n  n otes in t he 
“ N otes/ C urre nt  Me dicatio ns”  sectio n.  
7.  Sc ores t otalin g 1 2 p oints or m ore in dicate  pr o ba ble  de pressio n.  
 
S C O RI N G S Y S T E M  
9 9 9 9 = U na ble  t o e valuate;  0 = Abse nt;  1 = Mild  t o I nter mitte nt;  2 = Se vere.  
Sc ore greater  t ha n 1 2 = Pr o ba ble De pressio n  
A.  M O O D -R E L A T E D  SI G N S  
1.  An xi et y; a n xi o us e x pr essi o n, r u mi nati o n, worr yi n g   
 
9 9 9 9   
0  
1  
2 
2.  Sa d ness; s a d e x pr essi o n, s a d voi c e, t e arf ul ness     
 
9 9 9 9   
0  
1  
2 
3.  Lac k of r e acti o n t o pl e as a nt e ve nts   
  
  
 
9 9 9 9   
0  
1  
2 
4.  Irrit a bilit y; a n n o ye d, s h ort t e m per e d  
  
  
 
9 9 9 9   
0  
1  
2 
B.  B E H A VI O R A L  DI S T U R B A N C E  
5.  Agit ati o n; r estl ess ness, ha n d wri n gi n g,  hair p ulli n g   
 
9 9 9 9   
0  
1  
2 
6.  Ret ar dati o n; sl o w m o ve me nts, sl o w s pe e c h, sl o w r e acti o ns  
9 9 9 9   
0  
1  
2 
7.  M ulti pl e p h ysi c al c o m pl ai nts     
  
  
 
9 9 9 9   
0  
1  
2 
(s c or e 0 if gastr oi nt esti nal s y m pt o ms o nl y) 
8.  L oss of i nt er est; l ess i n vol ve d i n us ual acti viti es     
 
9 9 9 9   
0  
1  
2 
(s c or e 0 o nl y if c ha n ge o c c urr e d ac ut el y, i.e., i n l ess t ha n o ne m o nt h) 
C.  P H Y SI C A L  SI G N S  
9.  Ap petit e l oss; e ati n g l ess t ha n us ual   
  
  
 
9 9 9 9   
0  
1  
2 
1 0. Wei g ht l oss     
  
  
  
  
 
9 9 9 9   
0  
1  
2 
(s c or e 2 if gr e at er t ha n 5 p o u n ds i n o ne m o nt h) 
1 1. Lac k of e ner g y; f ati g ues e asil y, u na bl e t o s ust ai n acti viti es  
9 9 9 9   
0  
1  
2 
D.  C Y C LI C  F U N C TI O N S  
1 2. Di ur nal vari ati o n of m o o d; s y m pt o ms wors e i n t he m or ni n g  
9 9 9 9   
0  
1  
2 
1 3. Diffi c ult y f alli n g asl e e p; l at er t ha n us ual f or t his i n di vi d ual  
9 9 9 9   
0  
1  
2 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 0 9  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1 4. M ulti pl e a wa ke ni n gs d uri n g sl e e p   
  
  
 
9 9 9 9   
0  
1  
2 
1 5. Earl y m or ni n g a wa ke ni n g;  e arli er t ha n us ual f or t his i n di vi d ual  
9 9 9 9   
0  
1  
2 
E.  I D E A TI O N A L  DI S T U R B A N C E 
1 6. S ui ci dal; f e els lif e is n ot wort h li vi n g   
  
  
 
9 9 9 9   
0  
1  
2 
1 7. P o or s elf -est ee m; s elf-bl a me, s elf -de pr e ci ati o n, f e eli n gs of f ail ur e  9 9 9 9   
0  
1  
2 
1 8. P essi mis m; a nti ci pati o n of t he worst   
  
  
 
9 9 9 9   
0  
1  
2 
1 9. M o o d c o n gr ue nt del usi o ns; del usi o ns of p o vert y, ill ness or l oss  
9 9 9 9   
0  
1  
2 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 0  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 7: 
G E N E R A L  N E U R O L O GI C A L  E X A M  
T he Ge ner al Ne ur ol o gi cal E xa mi nati o n  will be perf or me d at t he ti me p oi nts s pecifi e d i n 
t he pr ot oc ol fl o w c hart. 
N ote t o t he I nvesti gat or: If, at a ny ti me, a b nor maliti es ar e o bs er ve d i n t he Ge ner al 
Ne ur ol o gi cal E xa m,  t he I nvesti gat or  s ho ul d d o a d diti o nal e xa m i nati o ns  as nee de d bas e d 
o n his or her me di cal j ud g me nt.  
T he Ge ner al Ne ur ol o gi cal E xa mi nati o n  i ncl udes all of t he mo d ul es liste d bel o w a nd is 
i nte nde d t o be a ge ner al s cr ee ni ng e xa mi nati o n  a nd s uffi ci e nt  f or t his tri al a nd s ubj ect 
p o p ul ati o n. 
( M o d ul e 1-Me n tal Stat us E xa mi nati o n  is not i ncl ude d beca us e t he c o nte nt is c o ver e d i n 
ot her ass ess me nts  i n t he  st ud y.)  
M O D U L E  2 – C R A NI A L  N E R V E  A S S E S S M E N T  
A.  
II – Vis ual  Fields  a n d ac uit y  
B.  
II, III – P u pil Size a n d Reactivit y  
C.  
III, I V, VI – E xtra oc ular  M o ve me nts (ra n ge of m otio n, s m o ot h p urs uit, sacca des, 
n ysta g m us) 
1.  
O bser ve f or n ysta g m us  d urin g  e ye m o ve me nts, increase d n ysta g m us  at t he e n d of 
gaze or ot her oc ulo m ot or  c ha n ges  ( mild  n ysta g m us  at e xtre mes  of gaze is n or mal).  
 
N ote directio n  of n ysta g m us  
D.  
V – Facial  Se nsatio n, Ja w  Stre n gt h 
E.  
VII – M uscles of Facial  E xpressio n  ( wrin kle  br o w, s q ueeze e yes s h ut, s mile)  
F.  
VIII – Au dit or y  Ac uit y  (assesse d usin g  a be d -side  scree nin g  test e. g. b y r u b bin g  fin gers  o n 
eac h side of s u bject’s hea d or b y w his perin g  n u m bers)  
G.  
I X – Ga g refle x  
H.  
X – S wal lo w 
I. 
XI – S h o ulder s hr u g  
J. 
T o n gue Pr otr usio n ( midline)  
Sc o re : left a n d right  (e xce pt f or G, H, J) 
Gra de :  N O R M A L  or I MP AI R E D  a n d describe a b n or malit y  
 
M O D U L E  3 - M O T O R S Y S T E M  
A.  
M uscle  T o ne  
1.  
As k t he v olu nteer  t o rela x.  
2.  
Fle x  a n d e xte n d  t he v olu nteer’s  elb o ws a n d k nees ( bilaterally).  
3.  
T here is a s mall,  c o ntin u o us  resista nce  t o passive  m o ve me nt.  
4.  
O bser ve f or in v olu ntar y  m o ve me nts (e. g., tre m or, tics, fascic ulatio ns).  O bser ve f or 
resista nce  t o passive m o ve me nt; o bser ve f or decrease d (flaccid)  or increase d 
(rigid/s pastic)  t o ne.  
Sc o re : left a n d right 
Gra de :  N O R M A L, I N C R E A S E D  or D E C R E A S E D 
B.  
M uscle  Stre n gt h  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
1.  
As k t he s u bject t o sta n d u p fr o m sittin g  wit h o ut  usin g  ha n ds  
Gra de :  N O R M A L, I M P AI R E D a n d describe  a b n or malit y 
2.  
T est pr o xi mal  li m b  stre n gt h  b y ha vin g  t he v olu nteer  fle x  a n d e xte n d t he k nees a n d 
elb o ws a gainst  y o ur resista nce.  
T est bilaterally,  a n d c o m pare o ne side t o t he ot her.  
Sc o re : left a n d right 
Gra de :  5/ 5: n or mal; 4/ 5: m o ve me nt a gainst  resista nce  i m paire d;  3/ 5: m o ve me nt 
a gainst  gra vit y  b ut n ot a gainst  resista nce;  2/ 5: visible  m o ve me nt b ut n ot a gainst 
gra vit y;  1/ 5: visible  c o ntractio n;  0/ 5: n o visible  activit y  
3.  
T est distal  li m b  stre n gt h b y ha vin g  t he v olu nteer c o n d uct d orsifle xio n  a n d pla ntar 
fle xio n  of t he v olu nteer’s  feet; fin ger  a b d uctio n  a n d ha n d grip  stre n gt h  a gainst y o ur 
resista nce. 
T est bilaterally,  a n d c o m pare o ne side t o t he ot her.  
Sc o re : left a n d right 
Gra de :  5/ 5: n or mal; 4/ 5: m o ve me nt a gainst  resista nce  i m paire d;  3/ 5: m o ve me nt 
a gainst  gra vit y  b ut n ot a gainst  resista nce;  2/ 5: visible  m o ve me nt b ut n ot a gainst 
gra vit y;  1/ 5: visible  c o ntractio n;  0/ 5: n o visible  activit y 
C.  
Pr o nat or Drift  
1.  
As k t he v olu nteer  t o h old b ot h ar ms straight  f or war d wit h, pal ms u p a n d e yes close d 
f or ~ 1 0-1 5 sec o n ds as t olerate d; watc h f or h o w well  t he ar m p ositio n  is maintaine d.  
2.  
I nstr uct t he v olu nteer t o kee p b ot h ar ms still  w hile  y o u ta p t he m bris kly  d o w n war d. 
T he v olu nteer  s h o uld n or mally  be a ble t o maintain  e xte nsio n  a n d s u pinatio n.  I na bilit y 
t o maintain  e xte nsio n  a n d s u pinatio n  (a n d drift  int o pr o natio n)  in dicates  a n u p per 
m ot or ne ur o n deficit.  
Sc o re : left a n d right 
Gra de :  N O R M A L  or I M P AI R E D  a n d describe a b n or malit y 
 
M O D U L E  4 - R E F L E X E S  
A.  
Bice ps 
B.  
K nee 
N ote: Ot her dee p te n d o n refle xes  ma y be teste d at PI's discretio n  (e. g. elb o w, wrist or  
Ac hilles  te n d o n)  
Sc o re : left a n d right 
Gra de :  N O R M A L, I N C R E A SE D,  D E C R E A S E D  or A B S E N T  
C.  
Ba bins ki 
Sc o re : left a n d right 
Gra de :  N O R M A L  or A B N O R M A L 
 
M O D U L E  5 - C O O R DI N A TI O N  A N D G AI T  
A.  
Ra pid, R h yt h mic  Alter natin g  M o ve me nts  
1.  
T estin g  eac h ha n d se parately, as k t he v olu nteer  t o ta p t he distal  t h u m b wit h t he tip of  
eac h fin ger,  in  se q ue nce, as fast as p ossible. 
Sc o re : left a n d right 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Gra de :  N O R M A L  or I M P AI R E D 
Re min der:  If t he ra pid alter nate  m o ve me nts are dist ur be d, t he s u bject will  be  as ke d t o 
strike his ha n d o n t he t high,  raise t he ha n d, t ur n it o ver a n d t he n strike  t he bac k of t he 
ha n d d o w n o n t he sa me place. ( T his test is  i m paire d  in cere bellar  disease, e xtra 
p yra midal  disease a n d u p per M N  wea k ness.) 
B.  
P oint-t o- P oint M o ve me nts  
1.  
As k t he v olu nteer  t o t o uc h y o ur in de x  fin ger  a n d t heir n ose alter nately  se veral  ti mes.  
M o ve y o ur fin ger  a b o ut as t he v olu nteer  perf or ms t his  tas k.  
Sc o re : left a n d right 
Gra de :  N O R M A L  or I M P AI R E D 
Re min der:  If t he p oint -t o-p oint  testin g  is dist ur be d,  t he s u bject will  be as ke d t o place 
o ne heel o n t he o p p osite  k nee a n d t he n r u n it d o w n t he s hin t o t he big  t oe. Re peat t his 
f or b ot h sides. (I m paire d  tests in dicate  cere bellar  disease.) 
C.  
R o m ber g 
1.  
As k t he v olu nteer  t o sta n d wit h b ot h feet t o get her  a n d e yes close d  f or 2 0 t o 3 0 
sec o n ds wit h o ut s u p p ort. 
2.  
Be pre pare d t o catc h t he v olu nteer if t he y are u nsta ble.  
Gra de :  N O R M A L or I M P AI R E D  
D.  
Gait  
1.  
As k t he v olu nteer  t o walk acr oss t he r o o m, t ur n a n d c o me bac k (assess p ost ure, 
bala nce, s win gin g  of ar ms a n d m o ve me nt of t he le gs).  
Gra de :  N O R M A L  or I M P AI R E D  a n d describe a b n or malit y 
2.  
As k t he v olu nteer  t o walk heel -t o-t oe  in a straight  line (ta n de m gait). 
Gra de :  N O R M A L  or I M P AI R E D  a n d describe a b n or malit y 
 
M O D U L E  6 - S E N S O R Y  
A.  
Pin pric k:  safet y pin t o uc he d lightly  t o s kin of f orear ms a n d le gs,  bilaterally.  
B.  
P ositio n  se nse: perce ptio n  of t h u m b a n d t oe m o ve me nt, bilaterally.  
Sc o re : left a n d right 
Gra de :  N O R M A L  O R I M P AI R E D a n d describe a b n or malit y  (f or eac h A t o F) 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 8: 
C O L U M BI A  S UI CI D E  S E V E RI T Y  R A TI N G  S C A L E  
S C R E E NI N G ( 1 4 J a n uar y  2 0 0 9) 
S UI CI D A L I D E A TI O N  
 
As k q uestio ns  1  a n d 2. If b ot h  are ne gative,  pr oc e e d  t o “ S uicidal  Be ha vior”  s e ctio n.  If t he a ns w er t o 
q uestio n  2 is  “ yes ”, as k q uestio ns  3,  4  a n d 5. If t he a ns w er t o  q uestio n  1 a n d/ or  2  is “ yes ”,  c o m plete 
“I nte nsit y  of I de atio n”  s e ctio n  belo w.  
P as t 2  M o nt hs   
1. Wis h t o be  D e a d  
S u bje ct  e n d ors es t h o u g hts  a b o ut  a wis h  t o be de a d or n ot  alive  a n y m ore,  or wis h  t o fall  asle e p a n d 
n ot  w a ke u p.  
H a v e  y o u wis he d y o u we re  de a d o r wis he d y o u c o ul d g o t o s le e p a n d n ot wa k e  u p ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
2. N o n -S pe cific A cti v e  S uici d al T h o u g hts   
Ge neral  n o n -s pe cific  t h o u g hts  of  w a ntin g  t o e n d  o ne’s life/c o m mit  s uicide  (e. g., “I’ ve t h o u g ht  a b o ut 
killi n g  m ys e lf” )  wit h o ut  t h o u g hts  of w a ys t o kill  o nes elf/ass ociate d  met h o ds,  inte nt,  or pla n  d urin g 
t he ass ess ment perio d.  
H a v e  y o u act u all y  h a d  a n y  t h o u g hts  of killi n g y o urs e lf?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
3. A cti v e  S uici d al I de ati o n wit h  A n y  M e t h o ds ( N ot Pl a n) wit h o ut  I nte nt t o A ct  
S u bje ct  e n d ors es t h o u g hts  of  s uicide  a n d has t h o u g ht  of  at le ast  o ne met h o d  d urin g  t he ass ess me nt 
perio d.  T his  is  differe nt  t ha n  a s pe cific  pla n  wit h  ti me,  pla c e or met h o d  details  w or ke d  o ut  (e. g. 
t h o u g ht  of met h o d  t o kill  s elf b ut  n ot  a s pe cific  pla n).  I nclu des  pers o n w h o  w o uld  s a y, “I t h o u g ht 
a b o ut  ta kin g  a n o ver d os e  b ut  I ne ver ma de a s pe cific  pla n  as t o w he n,  w here or  h o w I w o uld 
a ct ually  d o  it …a n d  I w o uld  ne ver g o t hr o u g h  wit h  it. ”  
H a v e  y o u be e n t hi n ki n g a b o ut h o w  y o u mi g ht d o t his ?  
If yes, des cribe:   
 
 
Ye s  
N o  
□  
□ 
4. A cti v e  S uici d al I de ati o n wit h  S o me  I nte nt t o A ct, wit h o ut  S pe cific Pl a n  
A ctive  s uicidal  t h o u g hts  of killin g  o nes elf  a n d s u bje ct  re p orts  ha vin g  s o me  inte nt  t o a ct o n  s uc h 
t h o u g hts,  as o p p os e d  t o “I ha ve t he t h o u g hts  b ut  I definitely  will  n ot  d o  a n yt hin g  a b o ut  t he m. ”  
H a v e  y o u h a d  t he s e  t h o u g hts a n d h a d  s o me  i nte nti o n of acti n g o n t he  m ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
5. A cti v e  S uici d al I de ati o n wit h  S pe cific Pl a n  a n d  I nte nt  
T h o u g hts  of  killin g  o nes elf  wit h  details  of pla n  f ully  or partially  w or ke d o ut  a n d  s u bje ct  has s o me 
inte nt  t o c arr y it  o ut.  
H a v e y o u st arte d t o wo r k o ut o r wo r k e d o ut t he det ails of h o w t o kill y o urs elf? D o y o u i nte n d 
t o c arr y  o ut t his  pl a n ?  
If yes, des cribe :  
Ye s  
N o  
□  
□ 
I N T E N SI T Y O F I D E A TI O N  
 
T he f ollo win g  fe at ures s h o uld  be rate d wit h  res pe ct t o  t he m ost  s e vere t y pe of  ide atio n  (i. e., 1 -5 
fr o m  a b o ve,  wit h  1 bein g  t he le ast s e vere a n d  5 bein g  t he m ost  s e vere). As k a b o ut  ti me  he/s he w as 
fe elin g  t he m ost  s uicidal.  
M os t Se ve re  I de ati o n:  
_ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _   
 
T y pe # ( 1 -5)  
Des c ri pti o n of I de ati o n  
 
M ost Se vere  
Fre q ue nc y  
H o w m a n y  ti me s  h a v e  y o u h a d  t he s e t h o u g hts ?  
( 1) Less t ha n o nc e a w e e k 
( 2) O nc e a w e e k 
( 3) 2-5 ti mes in  w e e k  
( 4) D a ily  or  a l m ost  da ily 
( 5) Ma n y  ti mes  e a c h da y  
_ _ _ _  
D ur ati o n  
W he n y o u h a v e  t he  t h o u g hts  h o w l o n g d o t he y l as t ?  
( 1) Fle etin g - fe w s e c o n ds or  min utes  
( 2) Less t ha n  1 h o ur/s o me  of  t he ti me  
( 3) 1-4  h o urs/a  lot  of  ti me  
( 4) 4-8  h o urs/ m ost  of  da y  
( 5) M ore t ha n  8 h o urs/ persiste nt  or c o ntin u o us  
_ _ _ _  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
C o ntr oll a bilit y  
C o ul d/c a n  y o u s t o p t hi n ki n g a b o ut killi n g y o urs e lf o r wa nti n g  t o die  if  y o u wa nt  t o ?  
( 1) Easily  a ble  t o  c o ntr ol  t h o u g hts  
( 2) Ca n c o ntr ol  t h o u g hts  wit h  little  diffic ult y  
( 3) Ca n c o ntr ol  t h o u g hts  wit h  s o me  diffic ult y  
( 4) Ca n c o ntr ol  t h o u g hts  wit h  a lot  of diffic ult y  
( 5) U na ble  t o  c o ntr ol  t h o u g hts  
( 0) D oes n ot  atte m pt t o  c o ntr ol  t h o u g hts  
_ _ _ _  
D ete rre nts  
A re  t he re  t hi n gs  - a n y o ne  o r a n yt hi n g  (e . g., fa mil y,  re li gi o n, p ai n  of de at h) - t h at  s t o p pe d y o u 
fr o m wa nti n g  t o die o r acti n g o n t h o u g hts of c o m mitti n g s uici de ?  
( 1) D eterre nts definitely  st o p pe d  y o u  fr o m  atte m ptin g  s uicide  
( 2) D eterre nts pr o ba bly  st o p ped  y o u  
( 3) U nc ertain  t hat deterre nts st o p pe d  y o u  
( 4) D eterre nts m ost  likely  did  n ot  st o p  y o u  
( 5) D eterre nts definitely  did  n ot st o p  y o u  
( 0) D oes n ot  a p ply  
_ _ _ _  
R e as o ns fo r I de ati o n  
W h at  s o rt of re as o ns  di d y o u h a v e  fo r  t hi n ki n g a b o ut wa nti n g  t o die  o r killi n g y o urs e lf? Was  
it t o e n d t he  p ai n  o r s t o p t he  wa y  y o u we re  fe e li n g (i n ot he r wo r ds  y o u c o ul d n’t g o o n li vi n g 
wit h  t his  p ai n  o r h o w  y o u we re  fe e li n g) o r was  it t o g e t atte nti o n, r e v e n ge o r a re acti o n fr o m 
ot he rs ? O r b ot h ?  
( 1) C o m pletely  t o get atte ntio n,  re ve n ge  or a re a ctio n  fr o m  ot hers  
( 2) M ostly  t o  get atte ntio n,  re ve n ge or a re a ctio n  fr o m  ot hers 
( 3) E q ually  t o get atte ntio n,  re ve n ge or a re a ctio n  fr o m  ot hers a n d  t o e n d/st o p  t he pain 
( 4) M ostly  t o  e n d or  st o p t he pain  ( y o u  c o uld n’t  g o  o n livin g  wit h  t he  pain  or h o w  y o u  w ere fe elin g)  
( 5) C o m pletely  t o e n d  or st o p  t he pain  ( y o u  c o uld n’t  g o  o n  livin g  wit h  t he pain  or h o w y o u  w ere 
fe e lin g)  
( 0) D oes n ot  a p ply  
_ _ _ _  
S UI CI D A L B E H A VI O R  
( C he c k all  t hat a p ply,  s o lo n g  as t hes e are s e parate e ve nts; m ust  as k a b o ut  all  t y pes)  
P as t 6  M o nt hs  
A ct u al Atte m pt:  
A  p ote ntia lly  s e lf -injurio us  a ct  c o m mitte d  wit h  at  le ast  s o me  wis h  t o  die, as a res ult of a ct. Be ha vior 
w as  in  part  t h o u g ht  of  as  met h o d  t o  kill  o nes elf.  I nte nt  d oes  n ot  ha ve  t o  be  1 0 0 %.  If  t here  is a n y 
inte nt/ desire  t o  die  ass ociate d  wit h  t he  a ct,  t he n  it  c a n  be  c o nsidere d  a n  a ct ual  s uicide  atte m pt. 
T he re   d o e s   n ot  h a v e   t o  be   a n y  i nj ur y  o r  h ar m ,  just  t he  p ote ntial  f or  injur y  or  har m.  If  pers o n 
p ulls  trig ger  w hile  g u n  is  in  m o ut h  b ut  g u n  is  br o ke n  s o  n o  injur y  res ults,  t his  is  c o nsidere d  a n 
atte m pt.  
I nferrin g  I nte nt:  E ve n  if  a n  in divid ual  de nies  inte nt/ wis h  t o  die,  it  ma y  be  inferre d  clinic ally  fr o m 
t he  be ha vior  or  circ u msta nc es.  F or  e xa m ple,  a  hig hly  let hal  a ct  t hat  is  cle arly  n ot  a n  a c cide nt  s o  n o 
ot her  inte nt  b ut  s uicide  c a n  be  inferre d  (e. g.,  g u ns h ot  t o  he a d,  ju m pin g  fr o m  win d o w  of  a  hig h 
flo or/st or y).  Als o,  if  s o me o ne  de nies  inte nt  t o  die,  b ut  t he y  t h o u g ht  t hat  w hat  t he y  did  c o uld  be 
let hal,  inte nt  ma y be inferre d.  
H a v e  y o u m a de  a s uici de  atte  m pt ?  
H a v e  y o u d o ne  a n yt hi n g  t o h ar m  y o urs e lf?  
H a v e  y o u d o ne  a n yt hi n g  d a n g e r o us  w he re  y o u c o ul d h a v e  die d ?  
 
W h at  di d y o u d o ?  
 
Di d y o u _ _ _ _ _ _ as a wa y t o e n d y o ur life ?  
 
Di d y o u wa nt  t o die (e v e n a little) w he n y o u _ _ _ _ _ ?  
 
We re y o u tr yi n g t o e n d y o ur life w he n y o u _ _ _ _ _ ?  
 
O r d i d  y o u t hi n k it was  p os s i ble  y o u c o ul d h a v e  die d fr o m _ _ _ _ _ ?  
O r di d  y o u d o it p ure l y  fo r  ot he r re as o ns  / wit h o ut A N Y  i nte nti o n of killi n g y o urs e lf (li k e  t o 
relie v e stress, fe el bette r,  g et s y m p at h y, o r g e t s o met hi n g e ls e t o h a p pe n) ? (Se lf -I njurio us 
Be ha vi or  wit h o ut  s uicidal  inte nt)  
If yes, des cribe:  
 
 
Ye s  
N o  
□  
□ 
 
 
 
T otal  # of  
Atte m pts  
_ _ _ _ _ _  
H as  s u bje ct e n g a g e d i n N o n -S uici d al  Se lf -I nj uri o us   B e h a vi o r ? 
Ye s  
N o  
□ 
□ 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
I nte rr u pte d Atte m pt:  
W he n  t he pers o n is  interr u pte d  ( b y a n o utside  circ u msta nc e)  fr o m  startin g  t he p ote ntially  s elf -
injurio us  a ct (if  n ot  f or t hat,  a ct ual  atte m pt  w o uld  ha ve oc c urre d).  
O ver d os e:  P ers o n has pills  in  ha n d  b ut is  st o p pe d  fr o m  in gestin g.  O nc e t he y  in gest  a n y  pill s,  t his 
be c o mes a n atte m pt  rat her t ha n a n interr u pte d  atte m pt. S h o otin g:  P ers o n has g u n  p ointe d  t o w ar d 
s elf,  g u n  is  ta ke n a w a y b y s o me o ne  els e, or  is s o me h o w  pre ve nte d fr o m  p ullin g  trig ger.  O nc e t he y 
p ull  t he trig ger,  e ve n if  t he g u n  fails  t o  fire,  it  is  a n atte m pt. J u m pin g:  P ers o n is  p ois e d  t o  ju m p,  is 
gra b be d  a n d ta ke n  d o w n  fr o m  le d ge.  H a n gin g:  P ers o n has n o os e  ar o u n d  ne c k b ut  has n ot  yet starte d 
t o ha n g - is  st o p pe d  fr o m  d oin g  s o.  
H as  t he re  be e n a ti me  w he n y o u s t arte d t o d o s o me t hi n g t o e n d y o ur life  b ut s o me o ne o r 
s o me t hi n g s t o p pe d y o u be fo re  y o u act u all y  di d a n yt hi n g ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
 
T otal  # of 
interr u pte d  
_ _ _ _ _ _  
A b o rte d Atte m pt:  
W he n  pers o n be gins  t o  ta ke ste ps t o w ar d ma kin g  a s uicide  atte m pt,  b ut  st o ps  t he ms elves  bef ore 
t he y  a ct ually  ha ve e n ga ge d  in  a n y s elf-destr uctive  be ha vior.  E xa m ples  are si milar  t o interr u pte d 
atte m pts,  e xc e pt t hat t he in divi d ua l  st o ps  hi m/ hers elf,  inste a d  of bein g  st o p pe d  b y  s o met hin g  els e.  
H as  t he re  be e n a ti me  w he n y o u s t arte d t o d o s o me t hi n g t o tr y t o e n d y o ur  life  b ut y o u 
s t o p pe d y o urs e lf be fo re  y o u act u all y  di d  a n yt hi n g ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
 
T otal  # of  
a b orte d  
_ _ _ _ _ _  
Pre p ar at o r y  A cts  o r B e h a vi o r:  
A cts or pre paratio n  t o w ar ds  i m mine ntl y  ma kin g  a s uicide  atte m pt. T his  c a n inclu de  a n yt hin g 
be y o n d  a ver balizatio n  or  t h o u g ht,  s uc h as ass e m blin g  a s pe cific  met h o d  (e. g., b u yin g  pills, 
p urc hasin g  a g u n)  or pre parin g  f or o ne’s de at h b y  s uicide  (e. g., givin g  t hin gs  a w a y, writin g  a 
s uicide  n ote).  
H a v e  y o u t a k e n a n y  s te ps t o war ds  m a ki n g a s uici de  atte  m pt o r pre p ari n g  t o kill y o urs e lf 
(s uc h as c olle cti n g pills, g e tti n g a g u n, gi vi n g v al u a ble s a wa y o r writi n g  a s uici de  n ote )?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
S uici d al  B e h a vi o r:  
S uicidal  be ha vior  w as pres e nt d urin g  t he ass ess me nt perio d?  
Ye s  
N o  
□ 
□ 
A ns we r fo r  A ct u al Atte  m pts  O nl y  
M ost Re c e nt 
Atte m pt  
D ate:  
M ost Let hal 
Atte m pt  
D ate:  
I nitia l/ First 
Atte m pt  
D ate:  
A ct u al Le t h alit y/ M e dic al D a m a g e :  
0. N o p h ysic al  da ma ge or ver y  min or  p h ysic al  da ma ge (e. g.,  s urfa c e 
s cratc hes).  
1. Min or  p h ysic al  da ma ge (e. g., let har gic  s pe e c h; first -de gre e  b ur ns; 
mild  ble e din g;  s prains).  
2. M o derate p h ysic al  da ma ge; me dic al  atte ntio n  ne e de d (e. g., 
c o ns cio us  b ut  sle e p y,  s o me w hat res p o nsive;  s e c o n d-de gre e  b ur ns; 
ble e din g  of  major  vess el).  
3. M o derately  s e vere p h ysic al  da ma ge; me dic al h os pitalizatio n  a n d 
likely  inte nsive  c are re q uire d (e. g., c o mat os e wit h refle xes inta ct;  t hir d-
de gre e b ur ns  less t ha n  2 0 % of b o d y;  e xte nsive  blo o d  loss  b ut  c a n 
re c o ver; major  fra ct ures).  
4. Se vere p h ysic al  da ma ge; me dic al h os pitalizati o n  wit h  inte nsive  c a re 
re q uire d  (e. g., c o mat os e wit h o ut  refle xes; t hir d-de gre e  b ur ns  o ver  2 0 % 
of b o d y;  e xte nsive  blo o d  loss  wit h  u nsta ble  vital  sig ns;  major  da ma ge 
t o a vital  are a).  
5. D e at h  
E nter C o de  
_ _ _ _ _ _  
E nter C o de  
_ _ _ _ _ _  
E nter C o de  
_ _ _ _ _ _  
P ote nti al Le t h alit y: O nl y A ns we r if A ct u al Le t h alit y = 0  
Likely  let halit y  of a ct ual  atte m pt if  n o  me dic al  da ma ge (t he  f ollo win g 
e xa m ples,  w hile  ha vin g  n o a ct ual  me dic al  da ma ge,  ha d  p ote ntial  f or 
ver y s erio us  let halit y:  p ut  g u n  in  m o ut h  a n d  p ulle d  t he trig ger  b ut  g u n 
fails  t o fire  s o n o me dic al  da ma ge; la yin g  o n  train  tra c ks wit h 
o nc o min g  train  b ut  p ulle d  a w a y bef ore  r u n o ver).  
0 = Be ha vior  n ot  likely  t o res ult  in  injur y  
1 = Be ha vior  likely  t o res ult  in  injur y  b ut n ot  likely  t o  c a us e de at h  
2 = Be ha vior  lik ely  t o res ult  in de at h des pite a vaila ble  me dic al  c are  
E nter C o de  
_ _ _ _ _ _  
E nter C o de  
_ _ _ _ _ _  
E nter C o de  
_ _ _ _ _ _  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
SI N C E L A S T VI SI T  ( 1 4 J a n uar y  2 0 0 9)  
S UI CI D A L I D E A TI O N  
As k q uestio ns  1  a n d 2. If b ot h  are ne gative,  pr oc e e d  t o “ S uicidal  Be ha vior”  s e ctio n.  If t he a ns w er 
t o q uestio n  2 is  “ yes ”,  as k q uestio ns  3,  4 a n d  5. If t he a ns w er t o q uestio n  1 a n d/ or  2 is  “ yes ”, 
c o m plete  “I nte nsit y  of I de atio n”  s e ctio n  belo w.  
Si nc e  L as t Visit  
1. Wis h t o be  D e a d  
S u bje ct  e n d ors es t h o u g hts  a b o ut  a wis h  t o be de a d or n ot  alive  a n y m ore,  or wis h  t o fall  asle e p a n d 
n ot  w a ke u p.  
H a v e  y o u wis he d y o u we re  de a d o r wis he d y o u c o ul d g o t o s le e p a n d n ot wa k e  u p ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
2. N o n -S pe cific A cti v e  S uici d al T h o u g hts   
Ge neral  n o n -s pe cific  t h o u g hts  of  w a ntin g  t o e n d  o ne’s life/c o m mit  s uicide  (e. g., “I’ ve t h o u g ht 
a b o ut  killi n g  m ys elf” )  wit h o ut  t h o u g hts  of w a ys t o kill  o nes elf/ass ociate d  met h o ds,  inte nt,  or pla n 
d urin g  t he ass ess me nt perio d.  
H a v e  y o u act u all y  h a d  a n y  t h o u g hts  of killi n g y o urs e lf?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
3. A cti v e  S uici d al I de ati o n wit h  A n y  M e t h o ds ( N ot Pl a n) wit h o ut  I nte nt t o A ct  
S u bje ct  e n d ors es t h o u g hts  of  s uicide  a n d has t h o u g ht  of  at le ast  o ne met h o d  d urin g  t he ass ess me nt 
perio d.  T his  is  differe nt  t ha n  a s pe cific  pla n  wit h  ti me,  pla c e or met h o d  details  w or ke d  o ut  (e. g., 
t h o u g ht  of met h o d  t o kill  s elf b ut  n ot  a s pe cific  pla n).  Inclu des  pers o n w h o  w o uld  s a y, “I t h o u g ht 
a b o ut  ta kin g  a n o ver d os e  b ut  I ne ver ma de a s pe cific  pla n  as t o w he n,  w here or  h o w I w o uld 
a ct ually  d o  it …a n d  I w o uld  ne ver g o t hr o u g h  wit h  it. ”  
H a v e  y o u be e n t hi n ki n g a b o ut h o w  y o u mi g ht d o t his ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
4. A cti v e  S uici d al I de ati o n wit h  S o me  I nte nt t o A ct, wit h o ut  S pe cific Pl a n  
A ctive  s uicidal  t h o u g hts  of killin g  o nes elf  a n d s u bje ct  re p orts  ha vin g  s o me  inte nt  t o a ct o n  s uc h 
t h o u g hts,  as o p p os e d  t o “I ha ve t he t h o u g hts  b ut  I definitely  will n ot  d o  a n yt hin g  a b o ut  t he m. ”  
H a v e  y o u h a d  t he s e  t h o u g hts a n d h a d  s o me  i nte nti o n of acti n g o n t he  m ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
5. A cti v e  S uici d al I de ati o n wit h  S pe cific Pl a n  a n d  I nte nt  
T h o u g hts  of  killin g  o nes elf  wit h  details  of pla n  f ully  or partially  w or ke d o ut  a n d  s u bje ct  has s o me 
inte nt  t o c arr y it  o ut.  
H a v e y o u st arte d t o wo r k o ut o r wo r k e d o ut t he det ails of h o w t o kill y o urs elf? D o y o u 
i nte n d t o c arr y  o ut t his  pl a n ?  
If yes, des cribe :  
Ye s  
N o  
□  
□ 
I N T E N SI T Y O F I D E A TI O N 
T he f ollo win g  fe at ures s h o uld  be rate d wit h  res pe ct t o  t he m ost  s e vere t y pe of  ide atio n  (i. e., 1 -5 
fr o m  a b o ve,  wit h  1 bein g  t he le ast s e vere a n d  5 bein g  t he m ost  s e vere). F or prior  t o  st u d y  e ntr y,  as k 
a b o ut  ti me he/s he  w as fe elin g  t he m ost  s uicidal.  
M os t Se ve re  I de ati o n:  
_ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
T y pe # ( 1 -5)  
D e s c ri pti o n of I de ati o n   
M ost Se vere  
Fre q ue nc y  
H o w m a n y  ti me s  h a v e  y o u h a d  t he s e t h o u g hts ?  
( 1) Less t ha n o nc e a w e e k ( 2) O nc e a w e e k ( 3) 2-5 ti mes  in  w e e k ( 4)  D aily  or al m ost  daily  ( 5) 
Ma n y ti mes e a c h da y  
_ _ _ _  
D ur ati o n  
W he n y o u h a v e  t he  t h o u g hts  h o w l o n g d o t he y l as t ?  
( 1) Fle etin g - fe w s e c o n ds or  min utes  ( 4) 4-8  h o urs/ m ost  of da y  
( 2) Less t ha n  1 h o ur/s o me  of  t he ti me  ( 5) M ore t ha n  8 h o urs/ persiste nt  or c o ntin u o us  
( 3) 1-4  h o urs/a  lot  of  ti me  
_ _ _ _  
C o ntr oll a bilit y  
C o ul d/c a n  y o u s t o p t hi n ki n g a b o ut killi n g y o urs e lf o r wa nti n g  t o die  if  y o u wa nt  t o ?  
( 1) Easily  a ble  t o  c o ntr ol  t h o ug hts  
( 2) Ca n c o ntr ol  t h o u g hts  wit h  little  diffic ult y 
( 3) Ca n c o ntr ol  t h o u g hts  wit h  s o me  diffic ult y 
( 4) Ca n c o ntr ol  t h o u g hts  wit h  a lot  of diffic ult y  
( 5) U na ble  t o  c o ntr ol  t h o u g hts  
( 0) D oes n ot  atte m pt t o  c o ntr ol  t h o u g hts  
_ _ _ _  
D ete rre nts  
A re  t he re  t hi n gs  - a n y o ne  o r a n yt hi n g  (e . g., fa mil y,  re li gi o n, p ai n  of de at h) - t h at  s t o p pe d y o u 
fr o m wa nti n g  t o die o r acti n g o n t h o u g hts of c o m mitti n g s uici de ?  
_ _ _ _  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
( 1) D eterre nts definitely  st o p pe d  y o u  fr o m  atte m ptin g  s uicide 
( 2) D eterre nts pr o ba bly  st o p pe d y o u  
( 3) U nc ertain  t hat deterre nts st o p pe d  y o u 
( 4) D eterre nts m ost  likely  did  n ot  st o p  y o u  
( 5) D eterre nts definitely  did  n ot st o p  y o u  
( 0) D oes n ot  a p ply  
R e as o ns fo r I de ati o n  
W h at  s o rt of re as o ns  di d y o u h a v e  fo r  t hi n ki n g a b o ut wa nti n g  t o die  o r killi n g y o urs e lf? Was  
it t o e n d t he  p ai n  o r s t o p t he  wa y  y o u we re  fe e li n g (i n ot he r wo r ds  y o u c o ul d n’t g o o n li vi n g 
wit h  t his  p ai n  o r h o w  y o u we re  fe e li n g) o r was  it t o g e t atte nti o n, r e v e n ge o r a re acti o n fr o m 
ot he rs ? O r b ot h ?  
( 1) C o m pletely  t o get atte ntio n,  re ve n ge  or a re a ctio n  fr o m  ot hers  
( 2) M ostly  t o  get atte ntio n,  re ve n ge or a re a ctio n  fr o m  ot hers  
( 3) E q ually  t o get atte ntio n,  re ve n ge or a re a ctio n  fr o m  ot hers a n d  t o e n d/st o p  t he pain 
( 4) M ostly  t o  e n d or  st o p t he pain  ( y o u  c o uld n’t  g o  o n livin g  wit h  t he  pain  or h o w  y o u  w ere fe elin g) 
( 5) C o m pletely  t o e n d  or st o p  t he pain  ( y o u  c o uld n’t  g o  o n  livin g  wit h  t he pain  or h o w y o u  w ere 
fe e lin g)  
( 0) D oes n ot  a p ply  
_ _ _ _  
S UI CI D A L B E H A VI O R  
( C he c k all  t hat a p ply,  s o lo n g  as t hes e are s e parate e ve nts; m ust  as k a b o ut  all  t y pes)  
Si nc e  L ast Visit  
A ct u al Atte m pt:  
A p ote ntia lly  s e lf -injurio us  a ct c o m mitte d  wit h  at le ast s o me  wis h  t o die, as a res ult of a ct. Be ha vior 
w as in  part  t h o u g ht  of as met h o d  t o  kill  o nes elf.  I nte nt  d oes n ot  ha ve t o  be 1 0 0 %.  If t here is a n y 
inte nt/ desire  t o die ass ociate d wit h t he a ct, t he n it c a n be c o nsidere d  a n a ct ual s uicide  atte m pt. 
T he re  d o e s n ot h a v e  t o be  a n y i nj ur y  o r h ar m ,  just  t he p ote ntial  f or  injur y  or har m.  If pers o n 
p ulls  trig ger  w hile  g u n  is  in  m o ut h  b ut  g u n  is  br o ke n  s o  n o injur y  res ults,  t his  is  c o nsidere d  a n 
atte m pt.  
I nferrin g  I nte nt:  E ve n if  a n in divi d ua l  de nies  inte nt/ wis h  t o  die,  it  ma y be inferre d  clinic ally  fr o m 
t he be ha vior  or  circ u msta nc es. F or  e xa m ple,  a hig hly  let hal  a ct t hat is  cle arly  n ot  a n a c cide nt  s o n o 
ot her  inte nt  b ut  s uicide  c a n be inferre d  (e. g., g u ns h ot  t o he a d,  ju m pin g  fr o m win d o w  of a hig h 
flo or/st or y).  Als o,  if  s o me o ne  de nies  inte nt  t o die,  b ut  t he y t h o u g ht  t hat w hat t he y did  c o uld  be 
let hal,  inte nt  ma y be inferre d.  
H a v e  y o u m a de  a s uici de  atte  m pt ?  
H a v e  y o u d o ne  a n yt hi n g  t o h ar m  y o urs e lf?  
H a v e  y o u d o ne  a n yt hi n g  d a n g e r o us  w he re  y o u c o ul d h a v e  die d ?  
 
W h at  di d y o u d o ?  
 
Di d y o u _ _ _ _ _ _ as a wa y t o e n d y o ur  life ?  
 
Di d y o u wa nt  t o die (e v e n a little) w he n y o u _ _ _ _ _ ?  
 
We re y o u tr yi n g t o e n d y o ur life w he n y o u _ _ _ _ _ ?  
 
O r d i d  y o u t hi n k it was  p os s i ble  y o u c o ul d h a v e  die d fr o m _ _ _ _ _ ?  
O r di d  y o u d o it p ure l y  fo r  ot he r re as o ns  / wit h o ut A N Y  i nte nti o n of ki lli n g y o urs e lf (li k e  t o 
re lie v e s tress, fe el be tte r, g e t s y m p at h y, o r g e t s o me t hi n g els e t o h a p pe n) ? (Se lf -I njurio us 
Be ha vior  wit h o ut  s uicidal  inte nt)  
If yes, des cribe:  
 
Ye s  
N o  
□ 
□  
 
 
T otal  # of  
Atte m pts  
_ _ _ _ _ _  
 
H as  s u bje ct e n g a g e d i n N o n -S uici d al Se lf -I nj uri o us   B e h a vi o r ? 
Ye s  
N o  
□ 
□ 
I nte rr u pte d Atte m pt:  
W he n  t he pers o n is  interr u pte d  ( b y a n o utside  circ u msta nc e)  fr o m  startin g  t he p ote ntially  s elf -
injurio us  a ct (if  n ot  f or t hat,  a ct ual  atte m pt  w o uld  ha ve oc c urre d).  
O ver d os e:  P ers o n has pills  in  ha n d  b ut is  st o p pe d  fr o m  in gestin g.  O nc e t he y  in gest  a n y  pills,  t his 
be c o mes a n atte m pt  rat her t ha n a n interr u pte d  atte m pt. S h o otin g:  P ers o n has g u n  p ointe d  t o w ar d 
s elf,  g u n  is  ta ke n a w a y b y s o me o ne  els e, or  is s o me h o w  pre ve nte d fr o m  p ullin g  trig ger.  O nc e t he y 
p ull  t he trig ger,  e ve n if  t he g u n  fails  t o  fire,  it  is  a n atte m pt. J u m pin g:  P ers o n is  p ois e d  t o  ju m p,  is 
gra b be d  a n d ta ke n  d o w n  fr o m  le d ge.  H a n gin g:  P ers o n has n o os e  ar o u n d  ne c k b ut  has n ot  yet starte d 
t o ha n g - is  st o p pe d  fr o m  d oin g  s o.  
H as  t he re  be e n a ti me  w he n y o u s t arte d t o d o s o me t hi n g t o e n d y o ur life  b ut s o me o ne o r 
s o me t hi n g s t o p pe d y o u be fo re  y o u act u all y  di d a n yt hi n g ?  
If yes, des cribe:  
Ye s  
N o  
□ 
□  
 
T otal  # of 
interr u pte d  
_ _ _ _ _ _  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 8  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A b o rte d Atte m pt:  
W he n  pers o n be gins  t o  ta ke ste ps t o w ar d ma kin g  a s uicide  atte m pt,  b ut  st o ps  t he ms elves  bef ore 
t he y  a ct ually  ha ve e n ga ge d  in  a n y s elf-destr uctive  be ha vior.  E xa m ples  are si milar  t o interr u pte d 
atte m pts,  e xc e pt t hat t he in divi d ua l  st o ps  hi m/ hers elf,  inste a d  of bein g  st o p pe d  b y  s o met hin g  els e.  
H as  t he re  be e n a ti me  w he n y o u s t arte d t o d o s o me t hi n g t o tr y t o e n d y o ur  life  b ut y o u 
s t o p pe d y o urs e lf be fo re  y o u act u all y  di d  a n yt hi n g ?  
If yes, des cribe:  
Ye s  
N o  
□  
□ 
 
T otal  # of  
a b orte d  
_ _ _ _ _ _  
Pre p ar at o r y  A cts  o r B e h a vi o r:  
A cts or pre paratio n  t o w ar ds  i m mine ntl y  ma kin g  a s uicide  atte m pt. T his  c a n inclu de  a n yt hin g 
be y o n d  a ver balizatio n  or  t h o u g ht,  s uc h as ass e m blin g  a s pe cific  met h o d  (e. g., b u yin g  pills, 
p urc hasin g  a g u n)  or pre parin g  f or o ne’s de at h b y  s uicide  (e. g., givin g  t hin gs  a w a y, writin g  a 
s uicide  n ote).  
H a v e  y o u t a k e n a n y  s te ps t o war ds  m a ki n g a s uici de  atte  m pt o r pre p ari n g  t o kill y o urs e lf 
(s uc h as c olle cti n g pills, g e tti n g a g u n, gi vi n g v al u a ble s a wa y o r writi n g  a s uici de  n ote )?  
If yes, des cribe:  
Ye s  
N o  
□ 
□  
S uici d al  B e h a vi o r:  
S uicidal  be ha vior  w as pres e nt d urin g  t he ass ess me nt perio d?  
Ye s  
N o  
□ 
□  
S uici de :  
Ye s  
N o  
□ 
□  
A N S W E R F O R A C T U A L A T T E M P T S O N L Y  
M ost Let hal 
Atte m pt  
D ate:  
A ct u al Le t h alit y/ M e dic al D a m a g e :  
0. N o p h ysic al  da ma ge or ver y  min or  p h ysic al  da ma ge (e. g.,  s urfa c e s cratc hes).  
1. Min or  p h ysic al  da ma ge (e. g., let har gic  s pe e c h; first -de gre e  b ur ns;  mild  ble e din g;  s prains).  
2. M o derate p h ysic al  da ma ge; me dic al  atte ntio n  ne e de d (e. g., c o ns cio us  b ut  sle e p y,  s o me w hat 
res p o nsive;  s e c o n d-de gre e b ur ns;  ble e din g  of major  vess el).  
3. M o derately  s e vere p h ysic al  da ma ge; me dic al h os pitalizatio n  a n d  likely  inte nsive  c are re q uire d 
(e. g., c o mat os e wit h refle xes inta ct; t hir d-de gre e  b ur ns  less  t ha n 2 0 % of  b o d y;  e xte nsive  blo o d  loss 
b ut c a n re c o ver; major  fra ct ures).  
4. Se vere p h ysic al  da ma ge; me dic al h os pitalizati o n  wit h  inte nsive  c are re q uire d  (e. g., c o mat os e 
wit h o ut  refle xes; t hir d -de gre e  b ur ns  o ver 2 0 %  of b o d y;  e xte nsive  blo o d  loss  wit h  u nsta ble  vital 
sig ns;  major da ma ge t o a vital  are a).  
5. D e at h  
E nter C o de  
_ _ _ _ _ _  
P ote nti al Le t h alit y: O nl y A ns we r if A ct u al Le t h alit y = 0  
Likely  let halit y  of a ct ual  atte m pt if  n o  me dic al  da ma ge (t he  f ollo win g  e xa m ples,  w hile  ha vin g  n o 
a ct ual me dic al  da ma ge, ha d p ote ntial  f or ver y s erio us  let halit y:  p ut  g u n  in  m o ut h  a n d p ulle d  t he 
trig ger  b ut  g u n  fails  t o  fire s o n o  me dic al  da ma ge;  la yin g  o n  train  tra c ks wit h  o nc o min g  train  b ut 
p ulle d  a w a y bef ore r u n o ver).  
0 = Be ha vior  n ot  likely  t o res ult  in  injur y  
1 = Be ha vior  likely  t o res ult in  injur y  b ut n ot  likely  t o  c a us e de at h  
2 = Be ha vior  likely  t o res ult  in de at h des pite a vaila ble  me dic al  c are  
E nter C o de  
_ _ _ _ _ _  
 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 1 9  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 9: 
M O DI FI E D  H A C HI N S KI  I S C H E MI C  S C A L E  
Rec or d t he pr es e nce or a bs e nce of t he cli ni cal feat ur es liste d bel o w a nd a d d t he p oi nt 
val ues assi gne d t o eac h feat ur e. S u m mati o n  of p oi nts pr o d uces a s c or e.  
 
Pres e nt  
A bs e nt  
a. A br upt o ns et of de me nti a 
e. g. r e p orte d r a pi d o ns et wit h ac kno wl e d g me nt  t hat gr a d ual 
c ha nges ma y  ha ve als o occ urr e d  
☐ 2 
☐ 0 
b.  Ste p wis e deteri or ati o n of de me nti a  
e. g. c o gniti ve decli ne, asi de fr o m o ns et, note d t o occ ur o ver 
da ys t o w ee ks a nd f oll o w e d b y pl atea us  
☐ 1 
☐ 0 
c. S o mati c c o mpl ai nts  
e. g. hea dac he, ti nnit us,  c hest pai n, mal ais e  
☐ 1 
☐ 0 
d.  E moti o nal  i nc o nti ne nce  
e. g. e pis o des of unc o ntr oll a bl e  cr yi ng  or l a ughter  i n 
r es p o ns e t o mi ni mal  pr o v ocati o n, or be yo nd t hat w hi c h 
w o ul d be c o nsi der e d a p pr o pri ate t o a gi ve n sit uati o n 
☐ 1 
☐ 0 
e. Hist or y or pr es e nce of hyperte nsi o n 
e. g. hist or y of bl o o d pr ess ur e of > 1 5 0/ 9 5 c o nfir me d up o n 
r e peate d meas ur es, or r e q uiri ng di et mo difi cati o n or 
tr eat me nt 
☐ 1 
☐ 0 
f. Hist or y of str o kes  
e. g. he mi par esis, a p hasi a  
☐ 2 
☐ 0 
g.  F ocal ne ur ol o gi cal s y mpt o ms  
e. g. tr a nsi e nt mo noc ul ar bli nd ness, unil ater al w ea kness or 
s e ns or y l oss; di pl o pi a l asti ng  ho urs;  s ei z ur es 
☐ 2 
☐ 0 
h.  F ocal ne ur ol o gi cal si gns ( o n e xa mi nati o n)  
e. g. as y m metri c  ri gi dit y or dee p te nd o n  r efl e xes, e xte ns or 
pl a ntar r es p o ns e, nysta g m us  
☐ 2 
☐ 0 
T O T A L S C O R E  
 
 
Ref e re nces:  
Hac hi ns ki  V C,  Iliff L D,  Zil hka  E, D u  B o ul a y  G H, Mc Allister V L, Mars hall J, R uss ell 
R W, S y mo n  L. “ Cer e br al bl o o d fl o w i n de me nti a.”  Ar c h Ne ur ol. 1 9 7 5; 3 2: 6 3 2- 7. 
 
M ols a P K, Palj ar vi L, Ri nne J O, Ri nne U K, Sa ko E. “ Vali dit y of cli ni cal di a gnosis i n 
de me nti a: a pr os pecti ve cli ni c o pat hol o gi cal st ud y.” J Ne ur ol Ne ur os ur g  Ps yc hi atr y. 
1 9 8 5; 4 8: 1 0 8 5- 9 0. 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 0  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 1 0: 
N A TI O N A L  I N S TI T U T E  O F N E U R O L O GI C A L  A N D C O M M U NI C A TI V E 
DI S E A S E S  A N D S T R O K E/ A L Z H EI M E R' S  DI S E A S E A N D R E L A T E D 
DI S O R D E R S  A S S O CI A TI O N  C RI T E RI A  F O R P R O B A B L E  A L Z H EI M E R’ S 
DI S E A S E  
 
I. T he criteri a f or t he cli ni cal di a gnosis of P R O B A B L E  Al z hei mer's dis eas e i ncl ude:  
•  de me nti a esta blis he d b y cli ni cal e xa mi nati o n  a nd d oc u me nte d  b y t he Mi ni – Me ntal 
Test; Bl ess e d De me nti a  Scal e, or s o me si mil ar e xa mi nati o n,  a nd c o nfir me d b y 
ne ur o ps yc hol o g i cal  tests; 
•  defi cits i n t w o or mor e ar eas of c o gniti o n; 
•  pr o gr essi ve w ors e ni ng of me mor y  a nd ot her c o gniti ve f uncti o ns;  
•  no dist ur ba nce of c o ns ci o us ness;  
•  o ns et bet w ee n a ges 4 0 a nd 9 0, most ofte n after a ge 6 5; a nd  
•  a bs e nce of s yste mi c dis or ders or ot her br ai n dis eas es t hat i n a nd of t he ms el ves c o ul d 
acc o unt f or t he pr o gr essi ve defi cits i n me mor y  a nd c o gniti o n.  
 
II. T he di a gnosis of P R O B A B L E  Al z hei mer‘s dis eas e is s up p orte d b y:  
•  pr o gr essi ve deteri or ati o n of s pecifi c c o gniti ve f uncti o ns  s uc h as l a ngua ge  ( a p hasi a),  
mot or s kills ( a pr a xi a), a nd per ce pti o ns ( a gn osi a); 
•  i mpair e d acti viti es of dail y li vi ng a nd alter e d patter ns of be ha vi or; 
•  fa mil y hist or y of si mil ar dis or ders, parti c ul arl y if c o nfir me d ne ur o pat hol o gi call y;  a nd 
•  l a b or at or y r es ults of: 
- 
nor mal  l u mbar p unct ur e as e val uate d b y sta ndar d tec hni q ues,  
- 
nor mal patter n or n o n- s pecifi c c ha nges i n E E G, s uc h as i ncr eas e d sl o w w a ve 
acti vit y, a nd  
•  e vi de nce of cer e br al atr o p hy o n C T wit h pr o gr essi o n d oc u me nte d  b y s eri al 
o bs er vati o n. 
 
III. Ot her cli ni cal feat ur es c o nsiste nt wit h t he  di a gnosis of P R O B A B L E  Al z hei mer‘s 
dis eas e, after e xcl usi o n of ca us es of de me nti a  ot her t ha n Al z hei mer‘s dis eas e, i ncl ude:  
•  pl atea us i n t he c o urs e of pr o gr essi o n of t he ill ness;  
•  ass oci ate d s y mpt o ms  of de pr essi o n, i ns o mni a, i nc o nti ne nce,  del usi o ns, ill usi o ns, 
hall uci nati o ns, catastr o p hi c ver bal, e moti o nal, or p hysi cal o ut b ursts, s e xual dis or ders, 
a nd w ei ght l oss; 
•  ot her ne ur ol o gi c a b nor maliti es i n s o me pati e nts, es peci all y wit h mor e a d va nce d 
dis eas e a nd i ncl udi ng mot or si gns s uc h as i ncr eas e d mus cl e t o ne, myocl o nus,  or gait 
dis or der; 
•  s ei z ur es i n a d va nce d dis eas e; a nd 
•  C T nor mal f or a ge.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
I V. Feat ur es t hat ma ke t he di a gnosis of P R O B A B L E  Al z hei mer‘s dis eas e uncertai n or 
unli kel y  i ncl ude:  
•  s ud de n, a p o pl ecti c o ns et; 
•  f ocal ne ur ol o gi c  fi ndi ngs  s uc h  as he mi par esis, s e ns or y l oss, vis ual fi el d defi cits, a nd 
i nc o or di nati o n  earl y i n t he  c o urs e of t he  ill ness; a nd 
•  s ei z ur es or gait dist ur ba nces at t he o ns et or ver y earl y i n t he c o urs e of t he ill ness. 
 
Ref e re nce:  
Mc K ha nn  G, Dr ac h ma n  D, F olstei n M, Katz ma n  R, Pri ce D, S ta dl a n E M. Cli ni cal 
di a gnosis of Al z hei mer’s dis eas e: r e p ort of t he NI N C D S -A D R D A  W or k  Gr o up under t he 
a us pi ces of De part me nt  of Healt h a nd H u ma n  Ser vi ces Tas k F or ce o n Al z hei mer’s 
Dis eas e. Ne ur ol o gy.  1 9 8 4 J ul; 3 4( 7): 9 3 9 - 4 4. 
 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A P P E N DI X 1 1: 
S U M M A R Y  O F C H A N G E S  F O R P R O T O C O L A M E N D M E N T  1  ( V E R SI O N  2) 
 
Pr ot oc ol Title:   
A P H A S E  2 A M U L TI C E N T E R,  R A N D O MI Z E D,  D O U B L E -B LI N D,  P A R A L L E L 
G R O U P,  2 6 -W E E K, P L A C E B O -C O N T R O L L E D  S T U D Y  O F 5 0 M G  A N D 1 0 0 M G O F 
S U V N -5 0 2  I N S U BJ E C T S  WI T H  M O D E R A T E  A L Z H EI M E R’ S DI S E A S E 
C U R R E N T L Y  T R E A T E D  WI T H  D O N E P E ZI L  H Y D R O C H L O RI D E  A N D 
M E M A N TI N E  H Y D R O C H L O RI D E  
 
T his a p pe ndi x s u m mari zes  t he c ha nges ma de t o t he Pr ot oc ol Versi o n 1. 0 iss ue d 
1 6 J ul y 2 0 1 5 i n Versi o n 2. 0 iss ue d 0 2 Mar c h 2 0 1 6. 
 
T he i nte gr ate d pr ot oc ol versi o n 2. 0 has bee n up date d t o all o w t he us e of Na mzari c ™ as 
c o mbi nati o n  Al z hei mer’s tr eat me nt,  as w ell as i ncl udi ng c ha nges  t o t he e xcl usi o n criteri a 
( # 8 & # 1 5), a nd t he f oll o w-up visit s c he d ul e f or s ubj ect s w ho dis c o nti nue  pr e mat ur el y.   
Ot her mi nor c ha nges  ha ve bee n i nc or p or ate d f or c o nsiste nc y  pr o vi di ng cl arifi cati o n i n 
s ecti o ns wit hi n t he pr ot oc ol. T he details ar e s u m mari ze d  bel o w:  
 
C ha nge 1:  All o w a nce f or N a mz aric ™  ( 2 8 mg me ma nti ne  H Cl e xt e n de d -rele as e / 1 0 
mg do ne pe z il  H Cl ) o nce dail y a n d  cl arific ati o n  of dr ug  i ngre die nts  i n 
N a me n da  X R ®  
Secti o ns of pr ot oc ol aff ect e d:  
•  S yno psis, Desi gn  
•  S yno psis, Tr eat me nt  
•  S yno psis, P o p ul ati o n  
•  3. 1 O ver vi e w 
•  4. 1 I ncl usi o n Criteri a 
•  4. 2 E xcl usi o n Criteri a 
•  4. 3 S ubj ect Wit hdr a w al a nd Re pl ace me nt  
•  5. 1. 2 O t her St ud y  Dr ugs 
•  5. 2. 2 Ot her St ud y  Dr ugs 
 
Sy n o psis, Desi g n ( 1 st p ar a gr a p h) a n d Secti o n 3. 1 ( 1st p ar a gr a p h): 
A d de d   t e xt: 
T his is a p has e 2 A, pr o of- of- c o nc e pt, … … … … … … a nd eit her me ma nti ne  H Cl ( 1 0 mg 
t wi ce dail y [ bi d]) or Na me nda  X R®  ( 2 8 mg me  ma nti ne  H Cl e xt e n de d-rele as e  q d) or 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
t he  c o m bi nati o n t he r a py, N a mz aric ™ ( 2 8  mg me ma nti ne  H Cl e xt e n de d -rele as e / 
1 0 mg do ne pe z il  H Cl ) q d . 
 
Sy n o psis, Tr e at me nt ( 2n d  p ar a gr a p h): 
A d de d  t e xt:  
T hr o ugho ut  t he st ud y, all s ubj ects … … … … … … … … …  or Na me nda  X R ®  ( 2 8 mg 
me  ma nti ne  H Cl e xt e n de d-rele as e  q d) or  t he  c o m bi nati o n t he r a py, N a mz aric ™ ( 2 8 
mg me ma nti ne H Cl e xt e n de d -rele as e / 1 0 mg do ne pe z il  H Cl ) q d . 
Sy n o psis, Tr e at me nt ( 5 t h or l ast p ar a gr a p h, 2 n d  s e nt e nce): 
A d de d  t e xt:  
Ge neri c f or mul ati o ns. ….. s ubj ects fr o m bas eli ne. S ubj ects tr eate d wit h Na me nda X R®  or 
N a mz aric ™ s ho ul d c o nti nue t o ta ke t heir o w n me di cati o n as pr es cri be d b y t heir 
pr es cri bi ng p hysi ci a n.  
 
Sy n o psis, P o p ul ati o n:  
A d de d  t e xt:  
T he st ud y p o p ul ati o n will … … … … … or Na me nda X R ®  ( 2 8 mg me  ma nti ne   H Cl  
e xt e n de d -rele as e  q d) or  t he  c o m bi nati o n t he r a py, N a mz aric ™ ( 2 8  mg  me  ma nti ne  
H Cl e xt e n de d -rele as e / 1 0 mg do ne pe z il  H Cl ) q d . 
 
Secti o n 4. 1 I ncl usi o n Crit eri a (I ncl usi o n C rit eri a # 6 a nd # 7): 
A d de d  t e xt:  
6.  M ust be r ecei vi ng tr eat me nt  wit h sta bl e d os es of d o ne pezil H Cl ( 1 0 mg q d), eit he r 
as 1 0 mg do ne pe z il  H Cl  o nl y or part of t he c o m bi nati o n  t he r a py, N a mz aric ™ 
( 2 8 mg  me ma nti ne  H Cl e xt e n de d -rele as e / 1 0 mg do ne pe z il  H Cl)  q d  f or at l east 
3 mo nt hs  pri or t o s cr ee ni ng  visit. S ubj ects ar e li kel y t o be mai ntai ne d  o n t his 1 0  mg 
dail y d os e of d o ne pezil H Cl or N a mz aric ™ f or t he e ntir e d ur ati o n of t he st ud y. 
7.  M ust be r ecei vi ng tr eat me nt  wit h sta bl e d os es of me ma nti ne  H Cl ( 1 0  mg bi d) or 
Na me nda  X R ®  ( 2 8 mg me ma nti ne  H Cl  e xt e n de d-rele as e  q d) or as part of t he  
c o m bi nati o n t he r a py, N a mz aric ™  ( 2 8 mg me ma nti ne  H Cl e xt e n de d -rele as e / 
1 0 mg do ne pe z il  H Cl ) q d  f or at l east 3 mo nt hs  pri or t o t he s cr ee ni ng visit, i n 
a d diti o n t o d o ne pezil H Cl  tr eat me nt.  S ubj ects ar e li kel y t o be mai ntai ne d  o n t heir 
c urr e nt d os e of me ma nti ne  H Cl or Na me nda X R ®  or N a mz aric ™ f or t he d ur ati o n 
of t he st ud y.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 4  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Secti o n 4. 2 Excl usi o n Crit eri a ( Excl usi o n Crit eri a  # 4 ): 
A d de d  t e xt:  
4.  Is ta ki ng  d os es of me ma nti ne  H Cl ot her tha n 1 0 mg  bi d or Na me nda X R ®  
(2 8 mg  me ma nti ne  H Cl e xt e n de d -rele as e  q d) or N a mz aric ™ ( 2 8 mg me  ma nti ne  
H Cl e xt e n de d -rele as e / 1 0 mg do ne pe z il  H Cl ) q d . 
 
Secti o n 4. 3 S u bj ect Wit h dr a w al a n d Re pl ace me nt ( 2 n d  p ar a gr a p h, 6t h b ull et):  
A d de d  t e xt:  
•  Tr eat me nt  wit h me ma nti ne  H Cl ca nnot be mai ntai ne d  at eit her 1 0 mg bi d of 
me ma nti ne  H Cl or 2 8 mg of me ma nti ne  H Cl  q d of Na me nda X R®  or as part of t he 
c o m bi nati o n  t he r a py  of N a mz aric ™ ( 2 8 mg me ma nti ne  H Cl e xt e n de d -rele as e / 1 0 
mg do ne pe z il  H Cl)  q d  
 
Secti o n 5. 1. 2 Ot her St u dy  Dr u gs ( 2n d  b ull et):  
A d de d  t e xt:  
•  me ma nti ne  H Cl 1 0 mg  bi d or Na me nda X R ®  ( 2 8 mg me ma nti ne H Cl e xt e n de d -
rele as e)  q d or N a mz aric ™  ( 2 8 mg  me ma nti ne H Cl e xt e n de d -rele as e / 1 0  mg 
do ne pe z il  H Cl)  q d . 
 
Secti o n 5. 2. 2 Ot her St u dy Dr u gs (( 1 st p ar a gr a p h a n d 3r d p ar a gr a p h): 
A d de d  t e xt:  
D o ne pezil H Cl ( 1 0 mg  q d), me ma nti ne  H Cl ( 1 0 mg  bi d) a nd Na me nda X R ®  
( 2 8 mg  me ma nti ne  H Cl e xt e n de d -rele as e q d) or N a mz aric ™ ( 2 8  mg  me  ma nti ne   H Cl 
e xt e n de d-rele as e / 1 0  mg do ne pe z il  H Cl )  q d s ho ul d be a d mi nister e d.. ….pr es cri bi ng 
p hysi ci a n.  
Ge neri c f or mul ati o ns   of d o ne pezil H Cl ( 1 0 mg) … … …..t he  s ubj ects fr o m bas eli ne.  
S ubj ects tr eate d wit h Na me nda X R ®  or N a maz aric ™ will c o nti nue  t o ta ke t heir o w n 
me di cati o n as dir ecte d b y t heir pr es cri bi ng p hysi ci a n.  
 
R ati o n al e f or c h a n ge:  A ne w c o mbi nati o n t her a p y  c o ntai ni ng 2 8 mg  me ma nti ne  H Cl 
e xte nde d -r el eas e a nd 1 0 mg  d o ne pezil H Cl (Na mazari c ™) q d  is no w a vail a bl e a nd 
pr es cri be d. T his c o mbi nat io n  f or mul ati o n  is si mil ar t o c o nc o mita nt  me di cati o n alr ea d y 
all o w e d i n t his st ud y a nd d oes not p os e a ny iss ues f or p ote nti al s ubj ects w ho w a nt t o 
parti ci pate i n t his st ud y.  T his c ha nge  all o ws s ubj ects  w ho ar e ta ki ng Na mazari c ™ t o 
parti ci pate a nd c o nti nue  t his me di cati o n  d uri ng  t he st ud y.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 5  of 1 4 3  
0 2 Mar c h 2 0 1 6  
C ha nge   2 : E xcl usi o n  crit e ri a  f or s u bj e cts w hos e  C -S D D s c ores s ug gest pr o ba ble 
de pre ssi o n  
Secti o n  of pr ot oc ol aff ect e d:  
•  4. 2 E xcl usi o n Criteri a 
 
Secti o n 4. 2 Excl usi o n Crit eri a ( Excl usi o n Crit eri a # 2 , 1st s e nt e nce): 
A d de d t e xt: 
2.  Has a di a gnosis of s c hi z o p hr e ni a, bi p ol ar dis or der or c urr e nt maj or de pr essi ve 
dis or der ( M D D)  or s u bj e cts w hos e  C-S D D s c ores  are  s ug gesti ve of pr o ba ble 
de pressi o n [t y pic all y s c ores ≥1 2] . 
 
R ati o n al e f or c h a n ge:  T he a d diti o n of t he C -S D D s c or es t o t he e xcl usi o n criteri a w as 
ma de t o pr o vi de a n a d diti o nal ass ess me nt t o ol t o be us e d b y i nvesti gat ors t o deter mi ne if 
a p ote nti al s ubj ect is c urr e ntl y de pr ess e d  a nd s ho ul d be e xcl ude d fr o m  t his st ud y.   
 
C ha nge   3 : Defi nit i o n  of c o nt r olle d  di a bet es f or s u bj e cts w hos e H b A 1c le vels are 
a bo ve 6. 5 % at Scre e ni ng f or e xcl usi o n p ur pos es  
Secti o n of pr ot oc ol aff ect e d:  
•  4. 2 E xcl usi o n Criteri a 
 
Secti o n 4. 2 Excl usi o n Crit eri a ( Excl usi o n Crit eri a # 8 ): 
Pre vi o us t e xt:  
8.  Has unc o ntr oll e d  T ype - 1 or T ype- 2 di a betes ( gl ycate d he mo gl o bi n  [ H b A 1c] 
a b o ve 6. 5 %). S ubj ect s w hos e  di a betes is c o ntr oll e d wit h me di cati o n a nd di et will  be 
all o w e d, pr o vi de d t heir H b A 1c is wit hi n t he nor mal r a nge . 
Re vis e d t e xt:  
8.  Has unc o ntr oll e d  T ype - 1 or T ype- 2 di a betes (gl ycate d he mo gl o bi n  [ H b A 1c] 
a b o ve 6. 5 %). A  s ubj ect wit h H B A 1c le vels u p t o 7. 5 % c a n  be  e nr olle d  if  t he  
i nvesti g at or belie ves t he s ubj ect’s di a betes is u n de r  c o nt r ol . 
 
R ati o n al e f or c h a n ge: Ma ny ol der s ubj ects wit h T ype 2 di a betes d o not ac hi e ve H b A 1c 
l e vels t hat ar e wit hi n nor mal li mits o nce t heir di a betes is c o nsi der e d under c o ntr ol or 
sta bili ze d wit h me di cati o n. T his c ha nge i n t he e xcl usi o n criteri a r efl ects t his cli ni cal 
o bs er vati o n a nd all o ws t he i nvesti gat or t o i ncl ude s ubj ects w hos e di a betes t he y c o ns i der 
under c o ntr ol or sta bili ze d, b ut o nl y f or s ubj ects w ho ha ve H b A 1c val ues ≤7. 5 %.  
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 6  of 1 4 3  
0 2 Mar c h 2 0 1 6  
C ha nge 4:  Cl arific ati o n  i n e xcl usi o n  crit e ri a  f or s u bj e cts wit h  l o w Vit a mi n  B- 1 2 
le vels  
Secti o n of pr ot oc ol aff ect e d:  
•  4. 2 E xcl usi o n Criteri a  
 
Secti o n 4. 2 Excl usi o n Crit eri a ( Excl usi o n Crit eri a # 1 5):  
Pre vi o us t e xt:  
1 5.  Has a b nor mal vita mi n B -1 2 l e vels. S ubj ects ta ki ng  vita mi n B - 1 2 s up pl e me nts  w ho 
ar e wit hi n nor mal li mits at s cr ee ni ng will be all o w e d.  
A d de d  t e xt: 
1 5.  Has a b nor mal vita mi n B - 1 2 l e vels t hat are l o we r t ha n nor mal li mits  a n d  re mai ns 
l o w  o n  re pe at t e sti ng. S ubj ects ta ki ng  vita mi n  B-1 2 s up pl e me nts  w ho ar e wit hi n 
nor mal li mits or a bo ve  at s cr ee ni ng or wit hi n  nor mal  li mits or a bo ve at re pe at 
t esti ng will be all o w e d.  
 
R ati o n al e f or c h a n ge:  T his c ha nge w as ma de t o cl arif y  t hat a s ubj ect wit h a vita mi n 
B- 1 2 val ue l o w er t ha n t he nor mal li mit c o ul d be all o w e d if r e peat testi ng r es ults i ndi cate d 
t hat  t he vita mi n  B-1 2 l e vels w er e wit hi n t he nor mal li mits. Als o all o ws  s ubj ects w ho 
ha ve hi gher  vita mi n  B -1 2 l e vels t ha n  nor mal li mi ts t o parti ci pate i n  t his st ud y.  
 
C ha nge  5: 
Si ngle -bli n d  me dic ati o n not  re q uire d f or s u bj e cts w ho t e r mi nat e t he 
st u dy  e arl y 
Secti o n of pr ot oc ol aff ect e d:  
•  7. 2. 7 Earl y Ter mi nati o n  a nd F oll o w- up Visits  
 
Secti o n 7. 2. 7 E arl y Ter mi n ati o n a n d F oll o w -u p Visits  ( 4t h s e nt e nce): 
Pre vi o us Te xt:  
If t he s ubj ect a gr ees, he/s he s ho ul d c o mpl ete t he w as h o ut peri o d a nd  a f oll o w-up visit 
4 w ee ks l ater.  
Re vis e d t e xt:  
If t he s ubj ect a gr ees, he/s he s ho ul d re t ur n  f or a f oll o w-up visit 4 w ee ks l ater.  
 
R ati o n al e f or  c h a n ge:  S ubj ects w ho ter mi nate  t he st ud y  pri or t o t he  si ngl e - bli nd pl ace b o 
w as ho ut peri o d ar e not e xpecte d t o ta ke a d diti o nal me di cati o n as s c he d ul e d d uri ng t he 
w as ho ut peri o d, b ut s ho ul d c o mpl ete t he Wee k 2 6 ( Visit 5) ass ess me nts i n t he  Earl y 
Ter mi nati o n  Visit a nd e nc o ur a ge d t o r et ur n 4 w ee ks l ater t o c o mpl ete t he ass ess me nts i n 
t he F oll o w- up Visit.  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 7  of 1 4 3  
0 2 Mar c h 2 0 1 6  
 
C ha nge  6: 
Re vis e d t e xt wit h  M o difie d  H ac hi ns ki  Is c he mic  Sc ale  ( M HI S) a n d 
re pl ace d  A p pe n di x  9 wit h  M HI S  
Secti o ns of pr ot oc ol aff ect e d:  
•  3. 1 O ver vi e w 
•  4. 1 I ncl usi o n Criteri a  
•  6. 4. 1. 2 M o difi e d Hac hi ns ki Is c he mi c Scal e  
•  7. 2. 1 Scr ee ni ng ( Visit 1, Da y - 2 8 t o - 1 4) 
•  A p pe ndi x 9  
Secti o n 3. 1 Over vi e w ( 3 r d p ar a gr a p h, 2 n d  s e nt e nce); Secti o n 4. 1 I ncl usi o n Crit eri a  
(I ncl usi o n Crit eri a # 5); Secti o n 6. 4. 1. 2 M o difi e d H ac hi ns ki Is c he mi c Sc al e ( he a di n g titl e 
a n d 1 st s e nt e nce); a nd Secti o n 7. 2. 1 Scr ee ni n g ( Visit 1, D ay - 2 8 t o - 1 4): 
Pre vi o us t e xt:  
Hac hi ns ki Is c he mi c Sc or e  
Re vis e d t e xt:  
M o difie d  H ac hi ns ki  Is c he mic  Sc ale  or t he a b br e vi ati o n: M HI S  
 
Ap pe n di x 9  M o difi e d H ac hi ns ki Is c he mi c Sc al e ( he a di n g titl e) 
Pre vi o us title:  
 
A P P E N DI X  9  
 
H A C HI N S KI  I S C H E MI C S C O R E  
Re vis e d title:  
A P P E N DI X  9  
M O DI FI E D  H A C HI N S KI  I S C H E MI C S C A L E  
 
Ap pe n di x 9  M o difi e d H ac hi ns ki Is c he mi c Sc al e ( ass ess me nt) 
Pre vi o us t e xt:  
F e at ur e  
Sc o r e  
F e at ur e  
Sc o re  
Abr u pt o ns et  
2  
E m oti o nal i nc o nti ne nc e  
1  
St e p wis e det eri or ati o n  
1  
Hist or y of h y pert e nsi o n  
1  
Fl uct uati n g c o urs e  
2  
Hist or y of str o kes  
2  
N o ct ur nal c o nf usi o n  
1  
E vi de nc e of ass o ci at e d at her os cl er osis  
1  
Rel ati ve pr es er vati o n of pers o nalit y  
1  
F o c al ne ur ol o gi c al s y m pt o ms  
2  
De pr essi o n  
1  
F o c al ne ur ol o gi c al si g ns  
2  
S o mati c c o m pl ai nts  
1  
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 8  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T O T A L  S C O R E:  
 
 
 
 
Re vis e d t e xt:  
See  A p pe ndi x 9 . 
R ati o n al e f or c h a n ge:  T he M o difi e d Hac hi ns ki Is c he mi c Scal e  w as us e d i nstea d of t he 
sta ndar d Hac hi ns ki Is c he mi c Scal e . 
 
C ha nge   7 : 
Cl arific ati o n  of w hic h  ass e ss me nts i n  t he  T a ble   3 Sc he d ule  of 
Pr oce d ure s  s ho ul d  be  pe rf or me d  first  i n  or de r  t o be  more   e fficie nt i n 
e li mi nati ng  s u bj e ct s w ho  do  not me et t he st u dy e nt r y crit e ri a at 
Scre e ni ng  a n d  B as e li ne  a n d t he assi g n me nt of o ne r at e r f or e ac h 
s u bj e ct f or s pe cific ass ess me nts 
Secti o n of pr ot oc ol aff ect e d:  
•  6. 1 Effi cac y Vari a bl es  
•  S yno psis , Sc he d ul e of Pr oce d ur es  
•  7. 1 Sc he d ul e of Pr oce d ur es  
•  7. 2 Pr oce d ur es b y Visit 
 
Secti o n 6. 1 Effi c acy V ari a bl es:  
A d de d  t e xt:  
It is st r o ngl y re c o m me n de d  t hat o ne r at e r is assi g ne d f or e ac h s u bj e ct f or e ac h of 
t he  effic ac y ass ess me nt s c ales des cri be d bel o w, s o t hat o ne r at e r s c ores a s u bj e ct’s 
ass ess me nt f or t he e ntire st u dy.  For e x a m ple, t he r at e r assi g ne d t o pe rf or m  t he 
M M S E w o ul d  r at e t hat s c ale f or all visits f or t hat s u bj e ct.  
 
Sy n o psis, Sc he d ul e of Pr oce d ur es a nd Secti o n 7. 1 Sc he d ul e of Pr oce d ur es ( T a bl e 3 
Sc he d ul e of Pr oce d ur es):  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 2 9  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Pre vi o us t a ble :  
T a ble  3: Sc he d ule   of Pr oce d ure s 
St u d y  pe ri o d  
Sc re e ni n g  
B as e li ne  
Tre at me nt Pe ri o d  
E n d of  Tre at me nt  
F oll o w -u p  
Ti me  
 
D a ys  -2 8 t o -1 4  
 
D a y  1  
We e k 4  
D a y  2 8 ± 2  
We e k 1 3  
D a y  9 1 ± 2  
We e k 2 6  
D a y 1 8 2 ± 3  
o r e arl y wit h dr a wal  
We e k 3 0  
D a y 2 1 0 ± 2  
Vis it n u m be r  
1 
2 
3 
4 
5 
6 
Pr o c e d ure s  
 
 
 
 
 
 
I nf or me d  Co ns e nt  
X 
 
 
 
 
 
I nclusio n  / E xclusio n  Criteria 
X  
X  
 
 
 
 
D e m o gra p hics,  Me dic al  Hist or y  
X  
X  
 
 
 
 
Prior  a n d C o nc o mita nt  Me dic atio ns  
X 
X 
X 
X 
X 
X 
M RI or C T Sc a n (if N e c ess ar y)  
X  
 
 
 
 
 
Blo o d  Sa m ple  f or A P O -E Ge n ot y pe  T e stin g 
 
X  
 
 
 
 
St u d y  Tre at me nt Dis pe ns atio n  a 
 
X  
X  
X  
X  
 
M M S E a n d A D A S -C o g  
X  
X  
X  
X  
X  
 
C D R- S B, A D C S -A D L, a n d N PI  
 
X 
X 
X 
X 
 
C- S D D  
X 
X 
X 
X 
X 
X 
Re vie w  of A Es  
X 
X 
X 
X 
X 
X 
La b orat or y  Tests  
X b 
X 
X c 
X 
X b 
X 
Blo o d  Press ure Me as ure me nts  
X  
X  
X  
X  
X  
X  
E C G  
X  
X  
X d 
X d 
X d 
X  
P h ysic al  a n d N e ur olo gic al  E xa minatio n  
X  
X  
X  
X  
X  
X  
C S S R S  
X  
X  
X  
X  
X  
X  
Plas ma L e vels of S U V N -5 0 2  a n d M 1  of S U V N -5 0 2  
 
 
X e 
 
X e 
 
Plas ma Le vels  of D o ne pe zil  a n d  M e ma ntine  
X 
 
X e 
 
X e 
 
(c o nti n u e d) 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 3 0  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T a ble   3: Sc he d ule   of Pr oce d ure s  ( C o nti n ue d)  
A D A S -C o g = Alz h ei mer’s Dis e ase Ass ess me nt S c al e; A D C S -A D L = Alz hei mer’s Dis e as e C o o per ati ve St u dy Acti vit y of D ail y Li vi n g; A E = a d v erse e ve nt; 
A P O -E = A p oli p o pr ot ei n E; C D R -S B = Cli ni c al De me nti a R ati n g S c al e – S u m of B o x es; C -S D D = C or nell S c al e of De pressi o n a n d De me nti a; C -S S R S = C ol u m bi a 
S ui ci d e S e verity R ati n g S c ale; C T = C o m p ut e d T o m o gr a p hy; E C G = El e ctr oc ar di o gr a m; M M S E = Mi ni -Me nt al St ate Ev al u ati o n; M RI = M a g n eti c Res o n a n ce 
I m a gi n g; N PI = Ne ur o ps yc hi atri c I n v e nt or y. 
a.  O n t h e d a y of t h e st u d y visits, s u bj ects will b e i nstr u ct e d n ot  t o t a ke t h eir tr e at me nt at h o me, as tr e at me nt will b e dis pe nse d at t h e st u dy ce nt er. 
b.  A uri n e pr e g n a ncy t est will b e d o n e at s cr e e ni n g a n d We e k 2 6 visit f or w o me n of c hil d be ari n g p ot e nti al. A p ositi ve uri ne t est  will b e c o nfir me d b y a 
s er u m pr e g n a ncy t est. 
c.  At We e k 4, l a b or at or y t ests will o nl y i n cl u d e li v er f u ncti o n t ests.  
d.  3 h o urs aft er st u dy tr e at me nt a d mi nistr ati o n, i.e. t h e a p pr oxi m at e ti me of m a xi m u m c o n ce ntr ati o n of S U V N -5 0 2.  
e. Pl as m a s a m pl es f or P K ass ess me nts will b e c oll ect e d b ef ore st u d y dr u gs ar e a d mi nist er e d t o t h e s u bje cts.  
 
 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 3 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
Re vis e d t a ble:  
T a ble  3: Sc he d ule   of Pr oce d ure s 
St u d y  pe ri o d  
Sc re e ni n g  
B as e li ne  
Tre at me nt Pe ri o d  
E n d of  Tre at me nt  
F oll o w -u p  
Ti me  
 
D a ys  -2 8 t o -1 4 a  
 
D a y  1  a 
We e k 4  
D a y  2 8 ± 2  
We e k 1 3  
D a y  9 1 ± 2  
We e k 2 6  
D a y 1 8 2 ± 3  
o r e arl y wit h dr a wal  
We e k 3 0  
D a y 2 1 0 ± 2  
Vis it n u m be r  
1 
2 
3 
4 
5 
6 
Pr o c e d ure s  
 
 
 
 
 
 
I nf or me d  Co ns e nt  
X 
 
 
 
 
 
I nclusio n  / E xclusio n  Criteria 
X  
X  
 
 
 
 
D e m o gra p hics,  Me dic al  Hist or y  
X  
X  
 
 
 
 
Prior  a n d C o nc o mita nt  Me dic atio ns  
X 
X 
X 
X 
X 
X 
M RI or C T Sc a n (if N e c ess ar y)  
X  
 
 
 
 
 
Blo o d  Sa m ple  f or A P O -E Ge n ot y pe  T e stin g 
 
X  
 
 
 
 
St u d y  Tre at me nt D is pe ns atio n b  
 
X 
X  
X  
X 
 
M M S E a n d A D A S -C o g  
X  
X  
X  
X  
X  
 
M o difie d H ac hi ns ki Is c he  mic  Sc ale  
X 
 
 
 
 
 
C D R -S B, A D C S -A D L, a n d N PI  
 
X  
X  
X  
X  
 
C -S D D  
X  
X  
X  
X  
X  
X  
C- S S R S  
X 
X 
X 
X 
X 
X 
Re vie w  of A Es  
X 
X 
X 
X 
X 
X 
La b orat or y  Tests  
X c 
X 
X d  
X 
X c 
X 
Blo o d  Press ure Me as ure me nts  
X  
X  
X  
X  
X  
X  
E C G  
X 
X 
X e  
X e  
X e  
X 
P h ysic al  a n d N e ur olo gic al  E xa minatio n  
X 
X 
X 
X 
X 
X 
Plas ma L e vels of S U V N -5 0 2  a n d M 1  of S U V N -5 0 2  
 
 
X f 
 
X f 
 
Plas ma Le vels  of D o ne pe zil  a n d  M e ma ntine  
X 
 
X f 
 
X f 
 
(c o nti n u e d) 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 3 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
T a ble   3: Sc he d ule   of Pr oce d ure s  ( C o nti n ue d) 
A D A S -C o g = Alz h ei mer’s Dis e ase Ass ess me nt S c al e; A D C S -A D L = Alz hei mer’s Dis e as e C o o per ati ve St u dy Acti vit y of D ail y Li vi n g; A E = a d v erse e ve nt; 
A P O -E = A p oli p o pr ot ei n E; C D R -S B = Cli ni c al De me nti a R ati n g S c al e – S u m of B o x es; C -S D D = C or nell S c al e of De pressi o n a n d De me nti a; C -S S R S = C ol u m bi a 
S ui ci d e S e verity R ati n g S c ale; C T = C o m p ut e d T o m o gr a p hy; E C G = El e ctr oc ar di o gr a m; M HI S = M o difi e d H a c hi ns ki Is c h e mi c S c al e; M M S E = Mi ni -Me nt al St ate 
Ev al u ati o n; M RI = M a g n etic Res o n a nce I m a gi n g; N PI = Ne ur o ps yc hi atri c I n v e nt or y.  
 
N ot e: It is str o n gl y r e c o m me n d e d t h at o ne r at er is assi g ne d f or e a c h s u bj ect f or e a c h of t he f oll o wi n g ass ess me nt s c al es s o t h at o ne r at er s c or es a s u bj ect ’s 
ass ess me nt f or t h e e ntir e st u d y: M M S E, A D A S-C o g , C D R-S B, A D C S -A D L, N PI, C -S D D, a n d C -S S R S.  
 
a.  F or Scr e e ni n g a n d B as eli ne Visits, t he f oll o wi n g ass ess me nts, i ncl u d e d i n st u d y e ntr y crit eri a, s h o ul d b e p erf or me d first i n or d er t o e x cl u d e s u bj ects 
a n d n ot w a st e ti me ass essi n g s u bj e cts w h o d o n ot me et t he st u d y e ntr y crit eri a: M M S E, t he M HI S , C-S D D, C -S S R S, E C G, pr e g n a nc y t est (f or 
w o me n of c hil d b e ari n g p ot e nti al), a n d l a b or at or y t ests.  
b.  O n t h e d a y of t h e st u d y visits, s u bj ects will b e i nstr u ct e d n ot t o t a ke t h eir tr e at me nt at h o me, as tr e at me nt will b e dis pe nse d at t h e st u dy ce nt er . 
c.  A uri n e pr e g n a ncy t est will b e d o n e at s cr e e ni n g a n d We e k 2 6 visit f or w o me n of c hil d be ari n g p ot e nti al. A p ositi ve uri ne t est  will b e c o nfir me d b y a 
s er u m pr e g n a ncy t est. 
d.  At We e k 4, l a b or at or y t ests will o nl y i n cl u d e li v er f u ncti o n t ests.  
e. 3 h o urs aft er st u dy tr e at me nt a d mi nistr ati o n, i.e. t h e a p pr oxi m at e ti me of m a xi m u m c o n ce ntr ati o n of S U V N -5 0 2.  
f. 
Pl as m a s a m pl es f or P K ass ess me nts will b e c oll ect e d b ef ore st u d y dr u gs ar e a d mi nist er e d t o t h e s u bje cts.  
 


















S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 4 1  of 1 4 3  
0 2 Mar c h 2 0 1 6  
R ati o n al e f or c h a n ges: T he A D A S -C o g  a nd A D C S -A D L  ass ess me nts i n t he a p pe ndi ces 
w er e not c o nsiste nt  wit h t he st ud y  w or ks heets a nd t he  e C R F. T he f or mat  i n t he 
w or ks heets a nd e C R F ar e easi er t o  s c or e a nd pr o vi de s c ori ng i nstr ucti o ns. 
 
C ha nge   9 : 
It e  ms  t hat re q uire d  cl arific ati o n  of w hat  w as i nt e n de d  i n  Ve rsi o n  1 of 
t he pr ot oc ol 
Secti o ns of pr ot oc ol aff ect e d:  
•  S yno psis , Desi gn 
•  S yno psis, Tr eat me nt  
•  3. 1 O ver vi e w 
•  5. 1. 1 I nvesti gati o nal  Tr eat me nt: S U V N -5 0 2  a nd Matc hi ng  Pl ace b o  
•  5. 1. 2 Ot her St ud y  Dr ugs 
•  5. 6 C o mpli a nce  
•  6. 2. 1. 4 Rec or di ng A d vers e E ve nts 
•  6. 2. 1. 5 Re p orti ng Seri o us A d vers e E ve nts 
•  7. 2. 1 Scr ee ni ng ( Visit 1, Da y - 2 8 t o - 1 4) 
•  7. 2. 2 Bas eli ne Visit ( Visit 2, Da y 1)  
•  7. 2. 3 Wee k 4 Visit ( Visit 3, Da y 2 8)  
•  7. 2. 4 Wee k 1 3 Visit ( Visit 4, Da y 9 1)  
•  7. 2. 5 Wee k 2 6 Visit ( Visit 5, Da y 1 8 2)  
•  7. 2. 6 Wee k 3 0 Visit ( Visit 6, Da y 2 1 0)  
•  8. 1. 1 Dis p ositi o n of S ubj ects 
 
It e m 1: C ha nges rel at e d t o w as ho ut pe ri o d: 
Sy n o psis, Desi g n ( 2 n d  p ar a gr a p h) a nd Secti o n 3. 1 Over vi e w ( 2n d  p ar a gr a p h): 
A d de d  t e xt:  
….. 4- w ee k si ngle-bli n d  pl ace b o w as ho ut peri o d.  
 
Sy n o psis, Tr e at me nt ( 3 r d p ar a gr a p h); Secti o n 3. 1 Over vi e w ( 2n d  p ar ar gr a p h, 1st s e nt e nce, 
a nd 7t h p ar a gr a p h, 1st s e nt e nce); Secti o n 5. 1. 1 I nvesti g ati o n al Tr e at me nt: S U V N - 5 0 2 a n d 
M at c hi n g Pl ace b o  ( 2n d  p ar a gr a p h); Secti o n 5. 1. 2 Ot her St u dy Dr u gs ( 1 st p ar a gr a p h); 
Secti o n 6. 2. 1. 4 Rec or di n g Advers e Eve nts ( 1 st p ar a gr a p h, 1st s e nt e nce); a nd Secti o n 
6. 2. 1. 5 Re p orti n g Seri o us Advers e Eve nts ( 4 t h p ar a gr a p h, 1st s e nte nce):  


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 4 2  of 1 4 3  
0 2 Mar c h 2 0 1 6  
A d de d  t e xt:  
….. si ngle-bli n d  pl ace bo  w as ho ut peri o d.  
 
It e  m  2: C ha nge   t o cl arif y  w he n  s u bj e cts s ho ul d  re t ur n  me dic ati o n  if  t he y 
dis c o nti n ue   t he  st u dy  me dic ati o n  e arl y:  
Secti o n 5. 6 C o m pli a nce ( 6 t h p ar a gr a p h, 1st s e nt e nce): 
A d de d  t e xt:  
F or s ubj ects w ho dis c o nti nue  st ud y  me di cati o n  earl y … … … … ….t he s ubj ect r et ur ns all 
st ud y me di cati o n at t he e arl y t e r mi nati o n  visit . 
 
R ati o n al e f or c h a n ge s: T hes e c ha nges w er e ma de f or cl arifi cati o n p ur p os es o nl y, r efl ect 
w as w hat i nte nde d  i n Versi o n  1 of t h e pr ot oc ol , a nd d o not i nv ol ve i n c ha nges  of t he 
st ud y desi gn or pr oce d ur es.  
It e m 3: C ha nge t o cl arif y defi niti o n  of st u dy c o m plet e rs: 
Secti o n 8. 1. 1 Dis p ositi o n of S u bj ects ( 2 n d  p ar a gr a p h): 
Pre vi o us t e xt:  
A s ubj ect w ho c o mpl etes all visits up t o Wee k 2 6 , will be c o nsi der e d t o ha ve c o mpl ete d 
t he st ud y. 
Re vis e d t e xt:  
A s ubj ect w ho c o mpl etes all visits up t o We e k 3 0 , will be c o nsi der e d t o ha ve c o mpl ete d 
t he st ud y. For e v al uati o n of effic ac y, a c o m plet e d s u bj e ct is defi ne d as a ny s u bj e ct 
w ho  c o m plet es all visi ts u p  t o We e k 2 6. 
 
It e  m  4: C ha nge t o cl arif y w hic h  ve rsi o n of t he C-S S R S  s ho ul d  be  us e d  f or  e ac h visit.  
Secti o n 7. 2. 1 Scr ee ni n g ( Visit 1, D ay - 2 8 t o -1 4) [ 2 n d  b ull et, l ast s u b -b ull et]:  
A d de d  t e xt:  
- 
C- S S R S  (s cre e ni ng ve rsi on)  
 
Secti o n 7. 2. 2 B as eli ne Visit ( Visit 2, D ay 1) [ 1 0t h b ull et], Secti o n 7. 2. 3 Week 4 Visit ( Visit 
3, D ay 2 8) [ 1 1t h b ull et], Secti o n 7. 2. 4 Week 1 3 Visit ( Visit 4, D ay 9 1) [ 1 0t h b ull et], 
Secti o n 7. 2. 5 Week 2 6 Visit ( Visit 5, D ay 1 8 2) [ 1 1t h b ull et], a nd Secti o n 7. 2. 6 Week 3 0 
Visit ( Visit 6,  D ay 2 1 0) [ 7t h b ull et]:  
A d de d  t e xt:  
•  C- S S R S (si nce l ast visit ve rsi o n) 
 


S u ve n Lif e Scie nc es Lt d  
Cli ni c al St u d y Pr ot o c ol  
 
C O N FI D E N TI A L  
 
Ve rsi o n 2  
1 4 3  of 1 4 3  
0 2 Mar c h 2 0 1 6  
C ha nge 1 0 : 
E dit ori al  c ha nges  
It e  m  1: C ha nge i n s c ori ng i n A p pe n di x  6 f or “ U na ble  t o e v al uat e ”  
Secti o n of pr ot oc ol aff ect e d:  
•  A p pe ndi x 6:  C or nell Scal e f or De pr essi o n A nd De me nti a 
 
Ap pe n di x 6: C or nell Sc al e f or De pr essi o n a n d De me nti a (s c ori n g s yst e m): 
Pre vi o us t e xt:  
a= U na ble  t o e valuate;  0 = Abse nt;  1 = Mild  t o I nter mitte nt;  2 = Se vere.  
… … … … … … … … … … … … … … … … … … … … … … … ….a  
0  
1  
2 
Re vis e d t e xt:  
9 9 9 9 = U na ble  t o e valuate;  0 = Abse nt;  1 = Mild  t o I nter mitte nt;  2 = Se vere.  
… … … … … … … … … … … … … … … … … … … … … … … …. 9 9 9 9   0  
1  
2 
 
R ati o n al e f or c h a n ge: T his c ha nge w as ma de t o t he A p pe ndi x 6 t o be c o nsiste nt wit h t he 
st ud y  w or ks heets a nd t he e C R F. 
 
It e m 2: C ha nge   of t he  a b bre vi ati o n  us e d f or Alz hei me r’s Dis e as e  Ass ess me nt Sc ale 
f or C o g niti ve Be ha vi or ( A D A S- C o g) t o be  c o nsist e nt t hr o ug ho ut  t he  doc u me nt 
Secti o n of pr ot oc ol aff ect e d:  
•  M ulti pl e  
De s cri pti o n  of c ha nge : M ulti pl e a b br e vi ati o ns w er e us e d f or Al z hei mer’s Dis eas e 
Ass ess me nt Scal e f or C o gniti ve Be ha vi or  : “ AD A Sc o g -1 1” a nd “ A D A S -C O G”.   All ha ve 
bee n c ha nge d t o A D A S -C o g.  
R ati o n al e f or c h a n ge: C o nsiste nc y.  
 
It e m 3: C ha nge   f or  t he  de s cri pti o n  of do ne pe z il  a n d  me  ma nti ne  t o do nepe zil H Cl 
a n d  me  ma nti ne   H Cl  
Secti o n of pr ot oc ol aff ect e d:  
•  M ulti pl e  
De s cri pti o n  of c ha nge : “ D o ne pezil ” w as c ha nge d  t o “ d o ne pezil H Cl ” a nd “ me ma nti ne” 
t o “ me ma nti ne  H Cl ”, e xce pt w he n des cri bi ng pl as ma or dr ug c o nce ntr ati o ns. 
 
R ati o n al e f or c h a n ge: C o nsiste nc y.  
 

SAP_001.pdf: 
 
 
Statistical Analysis Plan (SAP) 
Protocol Number: CTP2S1502HT6 
Protocol Title: A Phase 2A Multicenter, Randomized, Double-Blind, Parallel Group, 26-Week, Placebo-
Controlled Study of 50 mg and 100 mg of SUVN-502 in Subjects with Moderate Alzheimer’s Disease 
Currently Treated with Donepezil Hydrochloride and Memantine Hydrochloride 
NCT02580305 
Date: 31 October 2019