Assessment of the Efficacy and Safety of Molindone Hydrochloride Extended-Release for the Treatment of Impulsive Aggression in Pediatric Patients With Attention Deficit/Hyperactivity Disorder in Conjunction With Standard ADHD Treatment
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Sponsor: Supernus Pharmaceuticals, Inc.

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
TI TL E P A G E 
Pr ot oc ol N u m b er:  
8 1 0 P 3 0 1  
Titl e:  
A R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d St u dy t o Ev al u at e t h e 
Effic ac y a n d S af ety of M oli n d o n e Hy dr oc hl ori d e Ext e n d e d -R el e as e T a bl ets 
f or t h e Tr e at m e nt of I m p ulsi v e A g gr essi o n i n P e di atric P ati e nts wit h 
Att e nti o n D eficit/ Hy p er activit y  Dis or d er ( A D H D ) i n C o nj u ncti o n wit h 
S t a n d ar d A D H D T r e at m e nt 
S p o ns or:  
S u p er n us P h ar m ac e utic als, I nc.  
  
 
 
 
 
I N D n u m b er: 
1 0 6, 5 1 5  
I nv esti g ati o n al 
M e dici n al Pr o d uct:  
M oli n d o n e Hy dr oc hl ori d e Ext e n d e d -R el e as e T a bl ets (S P N -8 1 0)  
I n dic ati o n: 
Tr e at m e nt of I m p ulsiv e A g gr essi o n i n p ati e nts wit h Att e nti o n 
D eficit/ Hy p er activity  Dis or d er ( A D H D) i n c o nj u ncti o n wit h st a n d ar d A D H D 
tr e at m e nt 
Cli nic al C R O:  
 
 
 
M e dic al M o nit or  
 
 
 
 
                      
 
 
P h as e:  
3  
Pr ot oc ol V ersi o n:  
9 .0  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
R el e as e D at e:  
0 1 N o v  2 0 1 8  
G o o d Cli nic al Pr actic e 
( G C P) St at e m e nt: 
T his st u dy is t o b e p erf or m e d i n f ull c o m pli a nc e wit h I nt er n ati o n al 
C o nf er e nc e o n H ar m o niz ati o n (I C H) G C P a n d all a p plic a bl e l oc al r e g ul ati o ns.  
All r e q uir e d st u dy d oc u m e nt ati o n will b e arc hiv e d as r e q uir e d b y r e g ul at ory 
a ut h oriti es.  
 
I, t h e u n d ersi g n e d, h a v e r e a d t his pr ot oc ol a n d a gr e e t o c o n d uct t his tri al i n acc or d a nc e wit h all 
sti p ul ati o ns of t h e pr ot oc ol a n d i n acc or d a nc e wit h I C H G C P a n d all a p plic a bl e l oc al g ui d eli n es, 
i ncl u di n g t h e D ecl ar ati o n of H elsi n ki a n d all its acc e pt e d a m e n d m e nts t o d at e. 
 
 
 
 
 
 
Pri nci p al I n v esti g at or  
 
Si g n at ur e  
 
D at e  
 
  
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S U M M A R Y O F C H A N G E S 
T his s u m m ary t a bl e lists all cl arific ati o ns, a d mi nistr ativ e c h a n g es or a m e n d m e nts t o S u p er n us pr ot oc ol 
8 1 0 P 3 0 1. A d diti o ns ar e d e n ot e d by b ol d l ett ers a n d d el eti o ns b y stri k et hr o u g h. 
 
 
S ecti o n  
P a g e  
D escri pti o n of C h a n g e  
R ati o n al e  
C h a n g es t o 8 1 0 P 3 0 1 V 5. 0 D at e d 2 1 D ec 2 0 1 5  
Titl e P a g e  
1  
Pr ot oc ol v ersi o n a n d d at e w as u p d at e d  
A d mi nistr ati v e  
Si g n at ur e 
p a g e  
3  
T h e a ut h ors hi p f or r e vis e d  
F or cl arific ati o n  
S y n o psis  
1 0  
T h e f oll o wi n g w as a d d e d:  
 
 
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
S y n o psis  
1 1  
T h e f oll o wi n g w as c h a n g e d:  
T ot al s u bj ect d ur ati o n o n st u d y:  A p pr oxi m at el y 1 3  1 0 1 2  
w e e ks  
•  
Pr e -tr e at m e nt p h as e: U p t o 4 5 d a ys  4 6 w e e ks  
o  
Scr e e ni n g p eri o d:  U p t o 3 0 d a ys  2 - 4 w e eks  
o  
B as eli n e p eri o d:  At l e ast 1 5 d a ys  2 w e eks  
T o f acilit at e st u d y 
c o n d uct 
S y n o psis  
1 2  
T h e f oll o wi n g w as a d d e d:  
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
S y n o psis  
1 3  
T h e f oll o wi n g w as a d d e d:  
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 
List of 
A b br evi ati o ns  
1 9  
List of A b br e vi ati o ns w as u p d at e d t o i ncl u d e A d v ers e E v e nt 
of S p eci al I nt er est ( A E SI)  
F or cl arific ati o n  
2. 3  
2 5  
T h e f oll o wi n g w as c h a n g e d:  
 
 
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
3. 2  
2 6  
T h e f oll o wi n g w as c h a n g e d:  
F oll o wi n g scr e e ni n g, eli gi bl e s u bj ects will e nt er a t w o w e ek  
fl e xi bl e b as eli n e p eri o d, at w hic h ti m e t h e I A di ar y will b e 
iss u e d t o t h e s u bj ect’s pri m ar y c ar e gi v er.  At t h e e n d of t h e 
t w o w e e k  b as eli n e p eri o d, eli gi bl e s u bj ects w h os e pri m ar y 
c ar e gi v er h as m ai nt ai n e d at l e ast 8 0 % c o m pli a nc e wit h t h e I A 
di ar y will b e r a n d o miz e d 1: 1: 1 t o 1 8  m g/ d a y S P N -8 1 0, 
3 6  m g/ d a y S P N -8 1 0, or pl ac e b o.    
T o gi v e c ar e gi v ers t h e 
o p p ort u nit y t o i m pr o v e 
di ar y c o m pli a nc e  
3. 2. 1. 1  
2 6  
T h e f oll o wi n g w as c h a n g e d:  
Scr e e ni n g will t a k e pl ac e f or u p t o 2 8  4 5  d a ys pri or t o 
r a n d o miz ati o n a n d m a y b e c arri e d o ut o v er m or e t h a n o n e 
visit if n ec ess ar y.   
T o f acilit at e st u d y 
c o n d uct 
3. 2. 1. 1  
2 6  
T h e f oll o wi n g w as a d d e d:  
St aff at st u d y sit es ar e e nc o ur a g e d t o c o m pl et e scr e e ni n g 
pr oc e d ur es as e arl y as p ossi bl e t o pr o vi d e m or e fl e xi bilit y i n 
t h e B as eli n e P eri o d f or t h e c ar e gi v ers t o ac hi e v e I A di ar y 
c o m pli a nc e (s e e S ecti o n 3. 2. 1. 2).  
F or cl arific ati o n  
3. 2. 1. 2  
2 7  
T h e f oll o wi n g w as c h a n g e d:  
S u bj ects w h o m e et st u d y e ntr y r e q uir e m e nts will pr oc e e d t o 
t h e t w o w e e k  fl e xi bl e 1 5-d a y  b as eli n e p eri o d.  At Visit 2  
pri m ar y a n d ( if assi g n e d) s ec o n d ar y c ar e gi v ers will r ec ei v e 
tr ai ni n g o n t h e us e of t h e I A di ar y.  Aa n I A di ar y d evic e 
(L o g P a d) will b e iss u e d t o t h e pri m ar y c ar e gi v er.  T h e pri m ar y 
a n d (if assi g n e d) s ec o n d ar y c ar e gi v ers will r ec ei v e tr ai ni n g 
o n t h e us e of t h e I A di ar y.  E v er y eff ort will b e m a d e t o 
pr o vi d e a d e q u at e c ar e gi v er tr ai ni n g o n t h e us e of t h e I A 
di ar y at Visit 2 a n d ac k n o wl e d g e m e nt of tr ai ni n g will b e 
c a pt ur e d o n t h e d e vic e. T h e c ar e gi v er will b e i nstr uct e d t o 
T o gi v e c ar e gi v ers t h e 
o p p ort u nit y t o i m pr o v e 
di ar y c o m pli a nc e  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
m ai nt ai n t h e di ar y f or t w o w e eks.  At t h e e n d of t hi s p eri o d, 
c ar e gi v er c o m pli a nc e wit h t h e I A di ar y will b e ass ess e d.   
F oll o wi n g at l e ast 1 5 d a ys of I A di ar y us e, c ar e gi v er 
c o m pli a nc e wit h t h e I A di ar y will b e ass ess e d.  C o m pli a nc e 
will b e c alc ul at e d as t h e p erc e nt a g e of d a ys o v er t h e p ast 1 5 
d a ys  d uri n g t h e b as eli n e p eri o d f or w hic h a n e v e ni n g di ar y 
w as c o m pl et e d.  C o m pli a nc e of at l e ast 8 0 % m ust b e 
d e m o nstr at e d t o c o nti n u e i nt o t h e titr ati o n p eri o d a n d t o b e 
eli gi bl e f or r a n d o miz ati o n. C o m pli a nc e will b e m e as ur e d b y 
t h e p erc e nt a g e of e v e ni n g di ar y e ntri es c o m pl et e d d uri n g t h e 
b as eli n e p eri o d. S u bj ects w h os e c ar e gi v ers d e m o nstr at e at 
l e ast 8 0 % c o m pli a nc e will b e eli gi bl e f or r a n d o miz ati o n a n d 
c o nti n u e i nt o t h e titr ati o n p eri o d.  
S u bj ects w h os e c ar e gi v ers d o n ot r e ac h 8 0 % c o m pli a nc e 
d uri n g t h e first 1 5 d a ys of t h e B as eli n e P eri o d m a y b e 
all o w e d t o c o nti n u e t o us e t h e di ar y f or u p t o 1 5 a d diti o n al 
d a ys.  F or t h es e s u bj ects, c ar e gi v ers will r ec ei v e r e m e di al 
tr ai ni n g o n t h e us e of t h e I A di ar y.  D uri n g t his ti m e, 
c ar e gi v er c o m pli a nc e wit h t h e I A di ar y will b e m o nit or e d 
d ail y b y st u d y sit e p ers o n n el o v er t h e p ast 1 5 -d a ys as a 
“r olli n g wi n d o w”.  W h e n t h e c ar e gi v ers’ p erf or m a nc e wit h 
t h e I A di ar y i m pr o v es s uc h t h at t h e c ar e gi v ers ar e a bl e t o 
d e m o nstr at e at l e ast 8 0 % c o m pli a nc e o v er t h e p ast 1 5 -d a y 
r olli n g wi n d o w, t he s u bj ect will b e eli gi bl e f or 
r a n d o miz ati o n a n d all o w e d t o c o nti n u e i nt o t h e titr ati o n 
p eri o d.  
Alt h o u g h t h er e ar e u p t o 3 0 d a ys a v ail a bl e f or e ac h of t h e 
scr e e ni n g a n d t h e b as eli n e P eri o d, t h e t ot al d ur ati o n of 
scr e e ni n g a n d bas eli n e p eri o ds m a y n ot e xc e e d 4 5 d a ys.  
R escr e e ni n g  
As a g e n er al r ul e, r escr e e ni n g of s u bj ects is n ot all o w e d.  
T h e o nl y e xc e pti o n t o t his will b e f or s u bj ects w h o h a d 
f ail e d scr e e ni n g d u e t o c ar e gi v er n o n-c o m pli a nc e wit h t h e 
I A di ar y u n d er pr ot oc ol v ersi o n 5. 0. T h es e s u bj ects m a y be 
r escr e e n e d t o p artici p at e i n t h e st u d y u n d er pr ot oc ol 6. 0. 
T h es e s u bj ects will b e assi g n e d a n e w s u bj ect I D n u m b er 
a n d will c o m pl et e all st u d y scr e e ni n g pr oc e d ur es.  
3. 2. 4  
2 8  
T h e f oll o wi n g w as c h a n g e d:  
S u bj ects will r et ur n t o t h e st u d y sit e f or a fi n al visit, aft er 
c o m pl eti n g t h e 1 -w e ek T a p er/ C o n v ersi o n P eri o d.  T h os e 
F or cl arific ati o n  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
s u bj ects w h o el ect t o c o nti n u e i n t h e OL E st u d y will h a v e 
pr oc e d ur es p erf or m e d f or t h at st u d y as w ell.  All s u bj ects 
w h o disc o nti n u e e arl y will r et ur n t o t h e st u d y sit e f or a fi n al 
visit.  A n y  sS u bj ects w h o disc o nti n u e s fr o m t h e st u d y d uri n g 
t h e m ai nt e n a nc e p eri o d will b e off er e d a T a p er kit a n d will 
r et ur n t o t h e st u d y sit e f or a f oll o w-u p visit ( E O S).  S u bj ects 
w h o disc o nti n u e  d uri n g t h e titr ati o n p eri o d will n ot r ec ei v e 
a t a p er kit a n d will o nl y c o m pl et e t h e E O S pr oc e d ur es.   
Fi g ur e 1 a n d 
2  
2 9,  
3 0  
T h es e fi g ur es w er e u p d at e d wit h t h e n e w visit wi n d o ws a n d 
scr e e ni n g p eri o d 
U p d at e d as p er c h a n g es 
i n t h e pr ot oc ol 
4. 1. 1  
3 1  
T h e f oll o wi n g w as a d d e d:   
8 . 
α 2 - a dr e n er gic a g o nists ( e. g. cl o ni di n e a n d 
g u a nf aci n e) us e d f or a n y ot h er r e as o n e xc e pt f or 
m o n ot h er a p y tr e at m e nt f or A D H D ( e. g. a g gr essi o n or 
i ns o m ni a) m ust b e disc o nti n u e d at l e ast t w o w e e ks pri or t o 
Visit 2.  
T o  f acilit at e st u d y 
c o n d uct 
T a bl e 1  
3 3,  
3 4  
T a bl e 1 w as u p d at e d wit h t h e n e w visit wi n d o ws , scr e e ni n g 
p eri o d , b as eli n e p eri o d, a n d f o ot n ot es. D u e t o t h e a d diti o n of 
a n e w f o ot n ot e, t his s ecti o n h a d t o b e r e n u m b er e d  
U p d at e d as p er c h a n g es 
i n t h e pr ot oc ol 
T a bl e 1  
3 3,  
3 4  
T h e f oll o wi n g n e w f o ot n ot e “c” w as a d d e d f or Visit 3 
wi n d o w d a ys:  Visit 3 will occ ur at l e ast 1 5 d a ys f oll o wi n g 
Visit 2.  
 
F o ot n ot e “ g ” w as r e n u m b er e d t o “ h” a n d c h a n g e d as f oll o ws:  
g h       T ot al of 5 P K bl o o d s a m pl es will b e  o bt ai n e d o v er  o n e 
or t w o visits ( Visit 4 a n d/ or Visit 5)  t o b e di vi d e d b et w e e n 
Visit 4 a n d Visit 5.  
 
F o ot n ot e “ d ” w as r e n u m b er e d t o “ e” a n d c h a n g e d as f oll o ws:  
d e  
Di ar y c o m pli a nc e m ust b e at l e ast 8 0 % ( mi ni m u m of 
1 2 d a ys o ut of 1 4 1 5 ) t o q u alif y f or r a n d o miz ati o n. 
U p d at e d as p er c h a n g es 
i n t h e pr ot oc ol 
4. 2. 1  
3 5  
T h e f oll o wi n g w as c h a n g e d:  
S u bj ect scr e e ni n g pr oc e d ur es will b e p erf or m e d wit hi n 2 8  4 5  
d a ys pri or t o Visit 3 a n d m a y b e d o n e o n m or e t h a n o n e d ay.   
T o f acilit at e st u d y 
c o n d uct 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4. 2. 2  
3 5  
T h e f oll o wi n g w as c h a n g e d:   
Visit 2 will occ ur at l e ast 1 4  1 5  d a ys pri or t o Visit 3.   
T o f acilit at e st u d y 
c o n d uct 
4. 2. 2  
3 5  
T h e f oll o wi n g w as a d d e d :   
Pl e as e n ot e t h at, p er pr ot oc ol a n d wit hi n t h e E D C, Visit 1 
a n d Visit 2 m a y occ ur o n t h e s a m e d a y.  
F or cl arific ati o n  
4. 2. 3  
3 5  
T h e f oll o wi n g w as c h a n g e d:  
Visit 3 will occ ur at l e ast 1 4 1 5  d a ys f oll o wi n g Visit 2 acc or di n g 
t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es.  
T o f acilit at e st u d y 
c o n d uct 
4. 2. 3  
3 6  
T h e f oll o wi n g w as c h a n g e d:  
1 0.  
C oll ect uri n e s a m pl es f or uri n al ysis, uri n e dr u g 
scr e e n ( all s u bj ects), a n d pr e g n a nc y t est ( F O C P o nl y) 
F or cl arific ati o n  
4. 2. 4  
3 6  
T h e f oll o wi n g w as c h a n g e d:  
Visit 4 will occ ur 7 ( ± 1 2 ) d a ys f oll o wi n g Visit 3 acc or di n g t o 
t h e Sc h e d ul e of Visits a n d Pr oc e d ur es. 
T o f acilit at e st u d y 
c o n d uct 
4. 2. 5  
3 6  
T h e f oll o wi n g w as c h a n g e d:  
Visit 5 will occ ur 1 4 ( ± 1 2 ) d a ys f oll o wi n g Visit 3 acc or di n g t o 
t h e Sc h e d ul e of Visits a n d Pr oc e d ur es. 
T o f acilit at e st u d y 
c o n d uct 
4. 2. 6  
3 7  
T h e f oll o wi n g w as c h a n g e d:  
Visit 6 will occ ur 2 1 ( ± 1 3 ) d a ys f oll o wi n g Visit 5 acc or di n g t o 
t h e Sc h e d ul e of Visits a n d Pr oc e d ur es.   
T o f acilit at e st u d y 
c o n d uct 
4. 2. 8  
3 8  
T h e f oll o wi n g w as c h a n g e d:  
T h es e will i ncl u d e pr e a n d p ost -d os e s a m pl es o bt ai n e d o v er 
o n e visit ( Visit 4 or Visit 5) or c a n b e o bt ai n e d o v er t w o 
visits ( Visit 4 a n d Visit 5)  Bl o o d will b e dr a w n f or q u a ntit ati v e 
P K a n al ysis at Visit 4 a n d Visit 5.     
If t h e s u bj ect d eci d es t o c o m pl et e t h e P K s a m pli n g o v er o n e 
visit t h e n h e/s h e will arri v e at t h e cli nic i n t h e m or ni n g pri or 
t o t a ki n g t h e m or ni n g d os e.   
A P K s a m pl e  will b e dr a w n pr e -d os e; t h e n t h e d os e will b e 
o bs er v e d i n t h e cli nic.  P ost -d os e P K s a m pl es will b e t a k e n 
at a p pr o xi m at el y 1 h o ur,  2 h o urs, 4 h o urs a n d 6 h o urs aft er 
t h e ti m e of t h e o bs er v e d d os e.  P K s a m pl es s h o ul d b e 
o bt ai n e d wit hi n 1 5 mi n ut es of t h e 1 h o ur a n d 2 h o ur 
T o f acilit at e st u d y 
c o n d uct 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
ti m e p oi nts a n d wit hi n 3 0 mi n ut es of t h e 4 h o ur a n d 6 h o ur 
ti m e p oi nt. At o n e of t h es e visits, s u bj ects will arri v e at t h e 
cli nic i n t h e m or ni n g, pri or t o t a ki n g t h eir m or ni n g d os e.  A P K 
s a m pl e will b e dr a w n pr e d os e; t h e n t h e d os e will b e 
o bs er v e d i n t h e cli nic.  P ost d os e P K s a m pl es will b e t a k e n at 
a p pr oxi m at el y 1 h o ur a n d 2 h o urs aft er t h e ti m e of t h e 
o bs er v e d d os e.  P K s a m pl es s h o ul d b e o bt ai n e d wit hi n 1 5 
mi n ut es of t h e t ar g et e d ti m e p oi nts.   
If t h e s u bj ect d eci d es t o c o m e f or t h e P K s a m pli n g o v er t w o 
visits, t h e n o n o n e visit t h e s u bj ect will arri v e at t h e cli nic i n 
t h e m or ni n g, pri or t o t a ki n g t h eir m or ni n g d os e. A P K 
s a m pl e will b e dr a w n pr e-d os e; t h e n t h e d os e will b e 
o bs er v e d i n t h e cli nic .  P ost-d os e P K s a m pl es will b e t a k e n 
at a p pr o xi m at el y 1 h o ur a n d 2 h o urs aft er t h e ti m e of t h e 
o bs er v e d d os e. P K s a m pl es s h o ul d b e o bt ai n e d wit hi n 1 5 
mi n ut es of t h e t ar g et e d ti m e p oi nts.   
4. 4  
4 1  
T h e f oll o wi n g w as a d d e d:  
4. 4  
Pr o hi bit e d M e dic ati o ns:  
S u bj ects m a y  n ot b e o n a n y pr o hi bit e d m e dic ati o n w hil e o n 
st u d y as i n dic at e d i n t h e I ncl usi o n/ E xcl usi o n Crit eri a. T h es e 
m e dic ati o ns i ncl u d e:  
•  
α 2 - a dr e n er gic a g o nists ( e. g. cl o ni di n e a n d 
g u a nf aci n e) us e d f or a n y ot h er r e as o n e xc e pt 
f or m o n ot h er a p y tr e at m e nt f or A D H D  
•  
A nti -ps yc h otics i ncl u di n g ari pi pr az ol e,  
ris p eri d o n e, q u eti a pi n e, a n d zi pr asi d o n e  
•  
A ntic o n v uls a nts i ncl u di n g c ar b a m az e pi n e a n d 
v al pr oic aci d, a nti d e pr ess a nts, m o o d 
st a biliz ers i ncl u di n g lit hi u m, b e nz o di az e pi n es, 
c h oli n est er as e i n hi bit ors or a n y dr u g k n o w n 
t o i n hi bit C Y P 2 D 6 acti vit y 
•  
H er b al s u p pl e m e nts  
F or cl arific ati o n  
4. 5  
4 1  
T h e f oll o wi n g w as d el et e d:  
S u bj ects m a y n ot b e o n a n y pr o hi bit e d m e dic ati o n as 
i n dic at e d i n t h e I ncl usi o n/ Excl usi o n Crit eri a.  
F or cl arif ic ati o n 
5. 2. 1  
4 3  
T h e f oll o wi n g w as c h a n g e d:  
F or cl arific ati o n  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
•  
C GI -I, r el ati v e t o t h e c o n diti o n at b as eli n e  Visit 3 , 
will b e e v al u at e d b y t h e c ar e gi v er a n d b y t h e I n v esti g at or at 
e ac h p ost -b as eli n e visit o n a 7 -p oi nt sc al e wit h 1 = V er y m uc h 
i m pr o v e d, 2 = M uc h i m pr o v e d, 3 = Mi ni m all y i m pr o v e d, 4 = N o 
c h a n g e, 5 = Mi ni m all y w ors e, 6 = M uc h w ors e, a n d 7 = V er y 
m uc h w ors e.  
5. 3  
4 4  
T h e f oll o wi n g w as a d d e d:  
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
5. 3. 2  
4 4  
T h e f oll o wi n g w as a d d e d:  
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
5. 4. 2. 1  
4 7  
T h e f oll o wi n g w as c h a n g e d:  
All S A Es m ust b e r e p ort e d t o t h e Dr u g S af et y C o nt act wit hi n 
2 4 h o urs of first b ec o mi n g a w ar e of t h e S A E.  T h e I n v esti g at or 
m ust c o m pl et e a n S A E e C R F i n E D C  F or m  a n d i ncl u d e a 
d et ail e d d escri pti o n of t h e S A E, as w ell as ot h er a v ail a bl e 
i nf or m ati o n p erti n e nt t o t h e c as e ( e. g., h os pit al r ec or ds, 
a ut o psy r e p orts a n d ot h er r el ev a nt d oc u m e nts).  S h o ul d t h e 
sit e b e u n a bl e t o acc ess E D C, a p a p er S A E f or m  m ust b e 
c o m pl et e d a n d s e nt t o  
 Dr u g S af et y b y e m ail or f a x.  T h e 
i n v esti g at or will k e e p a c o p y of t his S A E R e p ort f or m o n fil e at 
t h e st u d y sit e. O nc e E D C b ec o m es a v ail a bl e, t h e sit e m ust 
c o m pl et e t h e S A E e C R F i n E D C.  
F or Cl arific ati o n  
5. 4. 2. 1  
4 8  
T h e E -m ail  a d dr ess f or dr u g s af et y c o nt act w as u p d at e d:  
 
A d mi nistr ati v e  
5. 4. 2. 2.  
4 8  
T h e f oll o wi n g w as a d d e d:  
T h e I n v esti g at or m ust c o m pl et e a Pr e g n a nc y O utc o m e F or m 
as a f oll o w u p.  
F or Cl arific ati o n  
5. 4. 2. 2  
4 8  
T h e f oll o wi n g w as c h a n g e d:  
Tr e at m e nt -e m er gi n g E P S ( e. g. a k at hisi a, d yst o ni a, 
P ar ki ns o nis m, t ar di v e d yski n esi a) a n d n e ur ol e ptic m ali g n a nt 
sy n dr o m e s h o ul d b e r e p ort e d t o t h e Dr u g S af et y C o nt act 
p ers o n(s) b y  c o m pl eti n g t h e A d v ers e E v e nt S p eci al I nt er est 
(A E SI ) e C R F i n E D C.  S h o ul d t h e sit e b e u n a bl e t o acc ess E D C, 
F or  Cl arific ati o n  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 
a p a p er A E SI f or m m ust b e c o m pl et e d a n d s e nt t o  
 Dr u g 
S af et y b y e m ail or f a x f axi n g or sc a n ni n g t h e a p pr o pri at e 
s o urc e d oc u m e nt ati o n wit hi n 2 4 h o urs of first b ec o mi n g 
a w ar e of t h e e v e nt.  O nc e E D C b ec o m es a v ail a bl e t h e sit e 
m ust c o m pl et e A E SI e C R F i n E D C. E P S i nci d e nc e will b e 
s u m m ariz e d a n d s h ar e d wit h st u d y I n v esti g at ors t hr o u g h o ut 
t h e tri al.   
5. 4. 4  
4 9  
T h e f oll o wi n g w as a d d e d:  
A s u bj ect will b e e xcl u d e d if t h e Scr e e ni n g bl o o d t est r es ults 
i n dic at es > 2 ti m es t h e u p p er li mit of n or m al ( UL N) of 
al a ni n e a mi n otr a nsf er as e ( AL T), as p art at e a mi n otr a nsf er as e 
( A S T), g a m m a gl ut a m yl tr a ns pe pti d as e ( G G T), a n d/ or s er u m 
cr e ati ni n e. L a b or at or y t ests will n ot b e r e p e at e d f or t h es e 
s u bj ects. 
A n y r e p e at l a b or at or y t esti n g will b e c o n d uct e d u n d er 
f asti n g c o n diti o n. 
F or Cl arific ati o n  
6. 5  
5 4  
T h e f oll o wi n g w as a d d e d:  
O nl y o n e ( pri m ar y) r e as o n f or st u d y disc o nti n u ati o n will b e 
r ec or d e d f or e ac h s u bj ect. 
F or Cl arific ati o n  
 
 
6. 9. 2  
5 6  
T h e f oll o wi n g w as c h a n g e d:  
T h e s ec o n d ar y e n d p oi nts ar e:  
1 . 
Act u al C ar e gi v er  C GI -I sc or e at Visit 6   
2.  
Act u al I n v esti g at or C GI -I sc or e at Visit 6 
2. 3.  
C h a n g e fr o m Visit 3 t o Visit 6 i n I n v esti g at or C GI -S 
sc or e 
3. 4.  
C h a n g e fr o m Visit 3 t o Visit 6 i n C H Q -2 8 sc or e 
5.  
C h a n g e fr o m Visit 3 t o Visit 6 i n P SI -4 -S F sc or es i n: 
a.  
P ar e nt al Distr ess  
b.  
P ar e nt -C hil d D ysf u ncti o n al I nt er acti o n  
a .c. 
Diffic ult C hil d  
4.  
C h a n g e fr o m Visit 3 t o Visit 6 i n C ar e gi v er c o m pl et e d 
C GI I  
F or Cl arific ati o n  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
5. 6.  
C h a n g e fr o m Visit 3 t o Visit 6 i n S N A P -I V A D H D 
sc or es i n: 
a.  
I n att e nti o n r ati n gs 
b.  
H y p er acti vit y/I m p ulsi vit y r ati n gs  
c. 
C o m bi n e d Sc al e r ati n gs  
6. 1 3  
6 0  
 T h e f oll o wi n g w as a d d e d:  
 
 
 
 
 
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
7. 4. 4  
6 4  
T h e f oll o wi n g w as a d d e d:  
 
 
 
T o u n d erst a n d ex p os ur e 
of m et a b olit es i n 
c hil dr e n 
C h a n g es t o 8 1 0 P 3 0 1 V 6 . 0 D at e d 2 1 J ul 2 0 1 6 
Titl e P a g e  
1  
Pr ot oc ol v ersi o n a n d d at e w as u p d at e d  
A d mi nistr ati v e  
Si g n at ur e 
P a g e  
3  
T h e si g n at ur e p a g e w as u p d at e d  
A d mi nistr ati v e  
S y n o psis  
1 5  
N u m b er of S u bj ects:  A p pr oxi m at el y 3 7 8 s u bj ects a g e d 6 -1 2  
1 7    y e ars (i ncl usi v e) will b e scr e e n e d t o ac hi e v e 2 9 1 s u bj ects  
r a n d o miz e d; 9 7 p er tr e at m e nt ar m 
Pr oc e d ur al  
S y n o psis  
1 5  
Crit eri a f or I ncl usi o n:  
Ot h er wis e h e alt h y m al e or f e m al e s u bj ects, a g e 6 t o  1 2  1 7 
y e ars  at t h e ti m e of scr e e ni n g wit h a pri m ar y di a g n osis o f 
A D H D a n d c urr e ntl y r ec ei vi n g m o n ot h er a p y tr e at m e nt wit h 
a n o pti miz e d F D A -a p pr o v e d A D H D m e dic ati o n.  I A will b e 
c o nfir m e d at scr e e ni n g usi n g R -M O A S a n d Viti ell o A g gr essi o n 
Sc al e.  
Pr oc e d ur al  
List of 
A b br evi ati o n  
2 5  
F O C P c h a n g e d t o F O C B P  
T o Cl arif y  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
3. 1  
3 1  
T h e pr es e nt st u d y is d esi g n e d t o e v al u at e t h e effic ac y, s af et y, 
a n d t ol er a bilit y of S P N -8 1 0 i n p ati e nts a g e d 6 t o 1 2  1 7 y e ars 
wit h A D H D a n d c o m or bi d I A, w h e n t a k e n i n c o nj u ncti o n wit h 
a st a n d ar d A D H D tr e at m e nt.  
Pr oc e d ur al  
3. 2  
3 2  
Pr ot oc ol 8 1 0 P 3 0 1 is a r a n d o miz e d, pl ac e b o-c o ntr oll e d, 
d o u bl e bli n d, m ultic e nt er, p ar all el gr o u p, fix e d d os e st u d y t o 
d e m o nstr at e t h e effic ac y, s af et y, a n d t ol er a bilit y of S P N -8 1 0 
i n t h e tr e at m e nt of I A i n p ati e nts a g e d 6-1 2  1 7  y e ars wit h 
A D H D i n c o nj u ncti o n wit h st a n d ar d A D H D t r e at m e nt. 
Pr oc e d ur al  
3. 2. 1. 1  
3 2  
T h e Viti ell o A g gr essi o n Sc al e will b e us e d t o e v al u at e s u bt y p e 
of a g gr essi o n ( pl a n n e d vs. i m p ulsi v e); o nl y t h os e c hil dr e n a n d 
a d ol esc e nts  w h o sc or e as pr e d o mi n a ntl y i m p ulsi v e will b e 
i ncl u d e d. 
Pr oc e d ur al  
3. 2. 1. 2  
3 3  
T h es e s u bj ects m a y b e r escr e e n e d t o p artici p at e i n t h e st u d y 
u n d er pr ot oc ol 6. 0 c urr e nt pr ot oc ol . 
T o Cl arif y  
4. 1  
3 7  
T h e t ar g et p o p ul ati o n will b e m al e a n d f e m al e s u bj ects a g e d 
6 t o 1 2  1 7  y e ars wit h I A a n d A D H D.  
Pr oc e d ur al  
4. 1. 1  
3 7  
1 . 
H e alt h y m al e or f e m al e s u bj ects, a g e 6 t o 1 2  1 7 
y e ars at t h e ti m e of scr e e ni n g.  
1 0. W ei g ht of at l e ast 2 0 k g  f or 6-1 2 y e ar ol d s u bj ects . 
Pr oc e d ur al  
4. 1. 2  
3 7, 3 8  
1.      B o d y M ass I n d ex ( B MI) i n l ess t h a n 2 5t h a n d a b o v e 9 9 t h 
p erc e ntil e or a b o v e  f or 1 3-1 7 y e ar ol d s u bj ects o nl y . 
9.  
Pr e g n a nc y or r ef us al t o pr actic e c o ntr ac e pti o n 
d uri n g t h e st u d y (f or f e m al e s u bj ects of c hil d b e ari n g 
p ot e nti al ) a n d s e x u all y acti v e m al es ). 
9. 1 0 . 
Cri mi n al arr est or r e p ort at l e ast 6 m o nt hs pri or t o 
Visit 2.  
 
T a bl e 1  
4 0  
f 
T o b e p erf or m e d f or f e m al e s u bj ects of c hil d b e ari n g 
p ot e nti al pri or t o a d mi nistr ati o n of first d os e of S M a n d will 
h a v e t o b e t est e d as n e g ati v e f or t h e s u bj ect t o c o nti n u e i n 
t h e st u d y. 
 
4. 2. 1. 4. 2. 3 
a n d 4. 2. 7  
4 1, 4 2, 
4 3  
F O C P c h a n g e d t o F O C B P  
T o Cl arify  
4. 2. 8  
4 4  
T h e f oll o wi n g p ar a gr a p h i n S ecti o n 4. 2. 8 w as d e pict e d as 
d el et e d b y a stri k et hr o u g h i n err or  i n t h e s u m m ar y of 
c h a n g es; t h e stri k et hr o u g h w as r e m o v e d:  
A d mi nistr ati v e  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
If t h e s u bj ect d eci d es t o c o m pl et e t h e P K s a m pli n g o v er o n e 
visit t h e n h e/s h e will arri v e at t h e cli nic i n t h e m or ni n g pri or 
t o t a ki n g t h e m or ni n g d os e. 
T a bl e 3  
5 6  
F O C P c h a n g e d t o F O C B P  
T o Cl arify  
C h a n g es t o 8 1 0 P 3 0 1 V 7. 0 D at e d 2 4 J ul 2 0 1 7  
Titl e P a g e  
1  
Pr ot oc ol v ersi o n a n d d at e w as u p d at e d  
A d mi nistr ati v e  
Si g n at ur e 
P a g e  
3  
T h e si g n at ur e p a g e w as u p d at e d a n d r evis e d  
A d mi nistr ati v e  
S y n o psis  
1 8  
N u m b er of S u bj ects:  A p pr oxi m at el y 3 7 8 s u bj ects a g e d 6 -1 7  
1 2   y e ars (i ncl usi v e) will b e scr e e n e d t o ac hi e v e 2 9 1 s u bj ects  
r a n d o miz e d; 9 7 p er tr e at m e nt ar m 
Pr oc e d ur al  
S y n o psis  
1 8  
Crit eri a f or I ncl usi o n: 
Ot h er wis e h e alt h y m al e or f e m al e s u bj ects, a g e 6 t o  1 7  1 2 
y e ars at t h e ti m e of scr e e ni n g wit h a pri m ar y di a g n osis of 
A D H D a n d c urr e ntl y r ec ei vi n g m o n ot h er a p y tr e at m e nt wit h 
a n o pti m iz e d F D A-a p pr o v e d A D H D m e dic ati o n.  I A will b e 
c o nfir m e d at scr e e ni n g usi n g R-M O A S a n d Viti ell o 
A g gr essi o n Sc al e.  
Pr oc e d ur al  
S y n o psis  
1 9  
Pri m ar y Effic ac y E n d p oi nt  
T h e pri m ar y effic ac y e n d p oi nt is t h e p erc e nt c h a n g e ( P C H M T) 
i n t h e fr e q u e nc y ( u n w ei g ht e d sc or e) of I A b e h a vi ors p er 7 
d a ys i n t h e M ai nt e n a nc e  Tr e at m e nt ( Titr ati o n a n d 
M ai nt e n a nc e)   p eri o d r el ati v e t o t h e B as eli n e p eri o d 
c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -missi n g I A 
di ar y d at a.    
T h e pri m ar y effic ac y e n d p oi nt P C H M T will b e c alc ul at e d b y 
P C H M T= 1 0 0 *( M T –  B)/ B, w h er e M T  a n d B ar e I A b e h a vi or 
fr e q u e nci es p er 7 d a ys d uri n g t h e m ai nt e n a nc e  Tr e at m e nt  
p eri o d a n d b as eli n e p eri o d , r es p ecti v el y. 
T o cl arify  
S y n o psis  
2 0  
H y p ot h es es:  
L et 1, 2, a n d 3 r e pr es e nt t h e m e di a n p erc e nt c h a n g e i n 
t h e fr e q u e nc y of I A b e h a vi ors p er 7 d a ys i n t h e M ai nt e n a nc e  
Tr e at m e nt  p eri o d r el ati v e t o t h e B as eli n e p eri o d i n t h e I T T 
p o p ul ati o n f or s u bj ects tr e at e d wit h Pl ac e b o, 1 8 m g a n d 3 6 
m g d os es of S P N -8 1 0, r es p ecti v el y.  T h e n ull ( H 0) a n d t h e 
alt er n ati v e ( H a) h y p ot h es es ar e as i n t h e f oll o wi n g. 
T o cl arify  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S y n o psis  
2 0  
H a n dli n g Missi n g D at a:  
F or t h e pri m ary effic acy e n d p oi nt, t h e fr e q u e ncy of I A 
b e h a vi ors d uri n g t h e  m ai nt e n a nc e  tr e at m e nt p eri o d will 
b e c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -missi n g I A 
di ar y d at a i n t h e m ai nt e n a nc e  tr e at m e nt p eri o d.  
T o cl arify  
S y n o psis  
2 1  
St atistic al M et h o ds:  
T h e pri m ar y effic ac y a n al ysis will b e b as e d o n t h e I T T 
p o p ul ati o n.  T h e pri m ar y effic ac y e n d p oi nt is t h e p erc e nt 
c h a n g e i n t h e fr e q u e nc y  ( u n w ei g ht e d sc or e) of I A b e h a vi ors 
p er 7 d a ys i n t h e M ai nt e n a nc e  Tr e at m e nt   p eri o d r el ati v e t o 
t h e B as eli n e p eri o d i n t h e I T T p o p ul ati o n c alc ul at e d o v er t h e 
n u m b er of d a ys wit h n o n -missi n g I A di ar y d at a.  
T o cl arify  
3. 1  
3 4  
T h e pr es e nt st u d y is d esi g n e d t o e v al u at e t h e effic ac y, 
s af et y, a n d t ol er a bilit y of S P N-8 1 0 i n p ati e nts a g e d 6 t o 1 7  
1 2 y e ars wit h A D H D a n d c o m or bi d I A, w h e n t a k e n i n 
c o nj u ncti o n wit h a st a n d ar d A D H D  tr e at m e nt. 
Pr oc e d ur al  
3. 2  
3 5  
Pr ot oc ol 8 1 0 P 3 0 1 is a r a n d o miz e d, pl ac e b o-c o ntr oll e d, 
d o u bl e bli n d, m ultic e nt er, p ar all el gr o u p, fix e d d os e st u d y t o 
d e m o nstr at e t h e effic ac y, s af et y, a n d t ol er a bilit y of S P N -8 1 0 
i n t h e tr e at m e nt of I A i n p ati e nts a g e d 6-1 7  1 2  y e ars wit h 
A D H D i n c o nj u ncti o n wit h st a n d ar d A D H D t r e at m e nt. 
Pr oc e d ur al  
3. 2. 1. 1  
3 5  
T h e Viti ell o A g gr essi o n Sc al e will b e us e d t o e v al u at e 
s u bt y p e of a g gr essi o n ( pl a n n e d vs. i m p ulsi v e); o nl y t h os e 
c hil dr e n a n d a d ol esc e nts  w h o sc or e as pr e d o mi n a ntl y 
i m p ulsi v e will b e i ncl u d e d. 
Pr oc e d ur al  
4. 1  
4 0  
T h e t ar g et p o p ul ati o n will b e m al e a n d f e m al e s u bj ects a g e d 
6 t o 1 7  1 2  y e ars wit h I A a n d A D H D.  
Pr oc e d ur al  
4. 1. 1  
4 0  
1 . 
H e alt h y m al e or f e m al e s u bj ects, a g e 6 t o 1 7  1 2  
y e ars at t h e ti m e of scr e e ni n g.  
1 0. W ei g ht of at l e ast 2 0 k g  f or 6 1 2 y e ar ol d s u bj ects . 
Pr oc e d ur al  
4. 1. 2  
4 0, 4 1  
1.      B o d y M ass I n d ex ( B MI) i n l ess t h a n 2 5t h a n d a b o v e 9 9 t h 
p erc e ntil e or  a b o v e  f or 1 3 1 7 y e ar ol d s u bj ects o nl y . 
 9. 1 0.  
Cri mi n al arr est or r e p ort at l e ast 6 m o nt hs pri or t o 
Visit 2.  
Pr oc e d ur al  
6. 2  
6 2  
F or t h e pri m ar y effic ac y e n d p oi nt, t h e fr e q u e nc y of I A 
b e h a vi ors d uri n g t h e m ai nt e n a nc e  tr e at m e nt p eri o d will b e 
T o cl arify  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -missi n g I A 
di ar y d at a i n t h e m ai nt e n a nc e  tr e at m e nt p eri o d.  
6. 9. 1  
6 4  
T h e pri m ar y effic ac y e n d p oi nt is t h e p erc e nt c h a n g e ( P C H M T) 
i n t h e fr e q u e nc y ( u n w ei g ht e d sc or e) of I A b e h a vi ors p er 7 
d a ys i n t h e M ai nt e n a nc e  Tr e at m e nt ( Titr ati o n a n d 
M ai nt e n a nc e)   p eri o d r el ati v e t o t h e B as eli n e p eri o d 
c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -missi n g I A 
di ar y d at a.    
T h e pri m ar y effic ac y e n d p oi nt P C H M T will b e c alc ul at e d b y 
P C H M T= 1 0 0 *( M T –  B)/ B, w h er e M T  a n d B ar e I A b e h a vi or 
fr e q u e nci es p er 7 d a ys d uri n g t h e m ai nt e n a nc e Tr e at m e nt  
p eri o d a n d b as eli n e p eri o d , r es p ecti v el y.  
L et 1, 2, a n d 3 r e pr es e nt t h e m e di a n p erc e nt c h a n g e i n 
t h e fr e q u e nc y of I A b e h a vi ors p er 7 d a ys i n t h e M ai nt e n a nc e  
Tr e at m e nt  p eri o d r el ati v e t o t h e B as eli n e p eri o d i n t h e I T T 
p o p ul ati o n f or s u bj ects tr e at e d wit h Pl ac e b o, 1 8 m g a n d 3 6 
m g d os es of S P N -8 1 0, r es p ecti v el y.   
T o cl arify  
6. 1 1  
6 7  
H o w e v er, t h e pri m ar y e n d p oi nt f or t his st u d y is p erc e nt 
c h a n g e i n t h e fr e q u e nc y  of I A i nci d e nc e p er 7 d a ys i n t h e 
M ai nt e n a nc e  Tr e at m e nt  ( Titr ati o n a n d M ai nt e n a nc e) 
p eri o d ( P C H M T) r el ati v e t o t h e B as eli n e p eri o d i n t h e I T T 
p o p ul ati o n c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -
missi n g I A di ar y d at a  
T o cl arify  
C h a n g es t o 8 1 0 P 3 0 1 V 8. 0 D at e d 0 7 N o v 2 0 1 7  
Titl e P a g e  
1, 2  
Pr ot oc ol v ersi o n a n d d at e w er e  u p d at e d  
A d mi nistr ati v e  
Si g n at ur e 
P a g e  
3  
T h e si g n at ur e p a g e w as u p d at e d  
A d mi nistr ati v e  
Pr ot oc ol 
S y n o psis  
1 9  
N u m b er of S u bj ects:  
A p pr oxi m at el y 4 2 6  3 7 8  s u bj ects a g e d 6-1 2 y e ars (i ncl usi v e) 
will b e scr e e n e d t o ac hi ev e 2 9 1  3 3 0  s u bj ects r a n d o miz e d; 9 7 
p er tr e at m e nt ar m  
R evis e d f oll o wi n g r e-
esti m ati o n of s a m pl e 
siz e 
Pr ot oc ol 
S y n o psis  
2 0  
S a m pl e siz e:  
B as e d o n r es ults fr o m t h e P h as e 2 st u d y, it is ass u m e d t h at 
t h e a v er a g e tr e at m e nt diff er e nc e b et w e e n S P N-8 1 0 d os e 
gr o u ps a n d pl ac e b o is 1 1. 5 1  1 5  wit h a c o m m o n st a n d ar d 
d evi ati o n of 2 7. 3.  A s a m pl e siz e of 1 3 2  7 7  s u bj ects p er ar m 
(2 6 4  2 3 1  s u bj ects f or 3  ar ms) will yi el d 9 0 % p o w er t o d et ect 
R evis e d f oll o wi n g r e-
esti m ati o n o f s a m pl e 
siz e 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
a n o n -z er o diff er e nc e b et w e e n t h e m e di a n of 1 8 m g or  3 6 
m g d os e gr o u p a n d t h e pl ac e b o usi n g t h e Wilc ox o n r a n k -
s u m t est wit h a 2-si d e d si g nific a nc e l e v el al p h a = 0. 0 5. 
It is ass u m e d t h at a p pr oxi m at el y 2 0 % of  s u bj ects will 
dr o p o ut b ef or e t h e c o m pl eti o n of t h e st u d y a n d h e nc e, a n 
a dj ust e d t ot al of 3 3 0  2 9 1  s u bj ects will b e r a n d o miz e d i n a 
1: 1 :1  r ati o t o o bt ai n 2 6 4  2 3 1  s u bj ects i n t h e I T T p o p ul ati o n 
at t h e c o m pl eti o n of t h e st u d y.  
4. 1  
4 1  
A p pr oxi m at el y 3 3 0 2 9 1  s u bj ects will b e r a n d o miz e d i n t his 
cli nic al i n v esti g ati o n.  
R evis e d f oll o wi n g r e-
esti m ati o n of s a m pl e 
siz e 
5. 2. 2  
5 3  
 
A D H D -C o m bi n e d s u bsc al e: t h e first t w o s u bsc al e s it e ms 
ar e c o m bi n e d  
E ac h s u bsc al e sc or e is t h e s u m a v er a g e  of t h e sc or es f or t h e 
i n di vi d u al it e ms i ncl u d e d i n t h e s u bsc al e. 
Cl arific ati o n  
6. 1 0  
6 8  
B as e d o n r es ults fr o m t h e P h as e 2 st u d y, it is ass u m e d t h at 
t h e a v er a g e tr e at m e nt diff er e nc e b et w e e n S P N -8 1 0 d os e 
gr o u ps a n d pl ac e b o is 1 1. 5 1  1 5  wit h a c o m m o n st a n d ar d 
d evi ati o n of 2 7. 3 . A s a m pl e siz e of 7 7  1 3 2  s u bj ects p er ar m 
(2 3 1  2 6 4  s u bj ects f or 3  ar ms) will yi el d 9 0 % p o w er t o d et ect 
a n o n -z er o diff er e nc e b et w e e n t h e m e di a n of 1 8 m g or  3 6 
m g d os e gr o u p a n d t h e pl ac e b o usi n g t h e Wilc ox o n r a n k -
s u m t est wit h a 2-si d e d si g nific a nc e l e v el al p h a = 0. 0 5. 
It is ass u m e d t h at a p pr oxi m at el y 2 0 % of  s u bj ects will 
dr o p o ut b ef or e t h e c o m pl eti o n of t h e st u d y a n d h e nc e, a n 
a dj ust e d t ot al of 2 9 1  3 3 0 s u bj ects will b e r a n d o miz e d i n a 
1: 1 :1  r ati o t o o bt ai n 2 3 1  2 6 4  s u bj ects i n t h e I T T p o p ul ati o n 
at t h e c o m pl eti o n of t h e st u d y.  
R evis e d f oll o wi n g r e-
esti m ati o n of s a m pl e 
siz e 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
CLI NI C AL P R O T O C OL S Y N O P SI S 
N a m e of C o m p a n y:  
S u p er n us P h ar m ac e utic als, I nc.  
I N D N u m b er:   1 0 6, 5 1 5  
N a m e of Pr o d uct:  M oli n d o n e Hy dr oc hl ori d e 
Ext e n d e d -R el e as e T a bl ets (S P N -8 1 0)  
N a m e of Acti v e I n gr e di e nt:  
M oli n d o n e Hy dr oc hl ori d e  
Pr ot oc ol N u m b er:  8 1 0 P 3 0 1  
P h as e of D e v el o p m e nt:  3  
F ull Titl e of St u d y:  A R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d St u dy t o Ev al u at e t h e Effic ac y 
a n d S af et y of M oli n d o n e Hy dr oc hl ori d e Ext e n d e d -R el e as e T a bl ets f or t h e Tr e at m e nt of I m p ulsiv e 
A g gr essi o n i n P e di atric P ati e nts wit h Att e nti o n D eficit/ Hy p er activity  Dis or d er ( A D H D ) i n 
C o nj u ncti o n wit h St a n d ar d A D H D T r e at m e nt 
I n v esti g at or(s) / C e nt er(s):  A p pr oxi m at el y 2 5 U S c e nt ers  
O bj ecti v es:  
Pri m ar y  
T h e pri m ar y o bj ecti v e is t o ass ess t h e effic acy a n d s af et y  of S P N -8 1 0 i n r e d uci n g t h e fr e q u e ncy of 
i m p ulsiv e a g gr essi o n (I A) b e h a vi ors i n p e di atric p ati e nts wit h A D H D w h e n t a k e n i n c o nj u ncti o n wit h 
st a n d ar d A D H D tr e at m e nt 
S ec o n d ar y  
T h e s ec o n d ary o bj ectiv es of t h e st u dy ar e t o ass ess t h e f oll o wi n g:  
 
t h e eff ect of S P N-8 1 0 o n t h e I n v esti g at or -r at e d Cli nic al Gl o b al I m pr essi o n –  I m pr ov e m ent 
Sc al e ( C GI -I)  
 
t h e eff ect of S P N-8 1 0 o n t h e Cli nic al Gl o b al I m pr essi o n –  S ev erity Sc al e ( C GI -S)  
 
t h e eff ect of S P N-8 1 0 o n t h e c hil d’s o v er all h e alt h as m e as ur e d b y t h e C hil d H e alt h 
Q u esti o n n air e P ar e nt F or m 2 8 -it e m ( C H Q-P F 2 8)  
 
t h e eff ect of tr e ati n g t h e c hil d wit h S P N-8 1 0 o n t h e p ar e nt -c hil d r el ati o ns hi p as m e as ur e d 
by t h e P ar e nti n g Str ess I n d ex –  S h ort F or m ( P SI -4 -S F)   
 
t h e eff ect of S P N-8 1 0 o n t h e C ar e giv er -r at e d C GI-I 
 
t h e eff ect of S P N-8 1 0 o n i n att e nti o n a n d h y p er activit y -i m p ulsivity m e as ur e d b y t h e S N A P-
I V R ati n g Sc al e  
T erti ary  
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
St u d y D esi g n:  D o u bl e -bli n d, pl ac e b o -c o ntr oll e d, r a n d o miz e d, p ar all el gr o u p st u dy 
N u m b er of S u bj ects:  A p pr oxi m at ely 4 2 6 s u bj ects a g e d 6 -1 2 y e ars (i ncl usi v e) will b e scr e e n e d t o 
ac hi e v e 3 3 0  s u bj ects r a n d o miz e d 
Crit eri a f or I ncl usi o n:  
Ot h er wis e h e alt h y m al e or f e m al e s u bj ects, a g e 6 t o 1 2  y e ars at t h e ti m e of scr e e ni n g  wit h a 
pri m ar y d i a g n osis of A D H D a n d c urr e ntl y r ec eivi n g m o n ot h er a py t r e at m e nt wit h a n  o pti miz e d F D A -
a p pr o v e d A D H D m e dic ati o n .  I A will b e c o nfir m e d at scr e e ni n g usi n g R-M O A S a n d Viti ell o 
A g gr essi o n Sc al e.  
Crit eri a f or E xcl usi o n:  
C urr e nt or lif eti m e di a g n osis of e pil e ps y, m aj or d e pr essi v e dis or d er, bi p ol ar dis or d er, sc hiz o p hr e ni a 
or r el at e d dis or d er, p ers o n alit y dis or d er, T o ur ett e’s dis or d er, or psyc h osis n ot ot h er wis e s p ecifi e d.   
C urr e ntl y m e eti n g D S M crit eri a f or a utis m s p ectr u m dis or d er, p er v asi v e d ev el o p m e nt al dis or d er, 
o bs essiv e c o m p ulsiv e dis or d er, p ost -tr a u m atic str ess dis or d er, or a ny ot h er a nxi et y dis or d er as 
pri m ar y di a g n osis.   K n o w n or s us p ect e d i nt elli g e nc e q u oti e nt (I Q) < 7 0, s uici d ality, pr e g n a ncy, or 
s u bst a nc e or alc o h ol a b us e. 
Tr e at m e nt, D os e, a n d M o d e of A d mi nistr ati o n:  
M oli n d o n e h y dr oc hl ori d e e xt e n d e d-rel e as e ta bl et d os a g e f or ms of 3 m g  a n d 9 m g  wit h  m atc hi n g 
pl ac e b o t a bl ets.  Tr e at m e nt t o b e a d mi nist er e d or all y t wic e d ail y  wit h or wit h o ut f o o d .  S u bj ects 
will b e f orc e -titr at e d o v er a p eri o d of 2 w e eks t o t h e ir fi n al r a n d o miz e d d os e. 
 
Tr e at m e nt 1:  pl ac e b o  
 
Tr e at m e nt 2:  1 8 m g  
 
Tr e at m e nt 3:  3 6 m g  
D ur ati o n of Tr e at m e nt a n d St u d y D ur ati o n:  
T ot al s u bj ect d ur ati o n o n st u dy:  A p pr oxi m at el y 1 3  w e e ks  
 
Pr e -tr e at m e nt p h as e: U p t o 4 5 d ays   
o  Scr e e ni n g p eri o d:  U p t o 3 0 d a ys  
o  B as eli n e p eri o d :  At l e ast 1 5 d a ys   
 
Tr e at m e nt p h as e:  5 w e e ks  
o  Titr ati o n  p eri o d :  2 w e e ks  
o  M ai nt e n a nc e  p eri o d :  3 w e e ks  
 
C o nv ersi o n/t a p er p h as e :  1  w e e k  
E n d p oi nts:  
Pri m ar y Effic acy E n d p oi nt  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T h e pri m ar y effic acy e n d p oi nt is t h e p erc e nt c h a n g e  ( P C HT) i n t h e fr e q u e ncy ( u n w ei g ht e d sc or e) of 
I A b e h avi ors p er 7 d ays i n t h e Tr e at m e nt ( Titr ati o n a n d M ai nt e n a nc e)   p eri o d r el ati v e t o t h e 
B as eli n e p eri o d c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n -missi n g I A di ary d at a.    
T h e pri m ar y effic acy e n d p oi nt P C H T will b e c alc ul at e d by P C H T= 1 0 0 *( T –  B) / B, w h er e T a n d B ar e I A 
b e h a vi or fr e q u e nci es p er 7 d a ys d uri n g t h e Tr e at m e nt p eri o d a n d b as eli n e p eri o d , r es p ecti v el y. T h e 
I A b e h avi or fr e q u e ncy p er 7 d a ys is d efi n e d as ( S U M/ D A Y) x 7, w h er e S U M  is  t h e t ot al of t h e I A 
b e h a vi ors  r e p ort e d i n t h e s u bj ect I A di ary, a n d D A Y is t h e n u m b er of d a ys wit h n o n-missi n g I A 
sc or e  i n t h e s u bj ect I A di ary d uri n g t h e s p ecifi e d st u dy p eri o d .  
 S ec o n d ary Effic ac y E n d p oi nts   
1.  I nv esti g at or-r at e d C GI-I 
2.  C GI -S  
3.  C H Q -P F 2 8  
4.  P SI -4 -S F  
5.  C ar e gi v er -r at e d C GI-I 
6.  S N A P -I V R ati n g Sc al e  
 
S af et y a n d T ol er a bilit y E n d p oi nts  
1.  A dv ers e ev e nts ( A E) 
2.  E xtr apyr a mi d al sy m pt o ms ( E P S) sc al es ( Si m ps o n -A n g us Sc al e, B ar n es Ak at hisi a Sc al e, 
A b n or m al I nv ol u nt ary M o v e m e nt Sc al e)  
3.  Cli nic al l a b or at ory t ests ( H e m at ol o gy, C h e mistry a n d Uri n al ysis)  
4.  E C Gs  
5.  Vit al si g ns  
6.  C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( C -S S R S)  
7.  I nfr e q u e nt B e h avi ors C h ecklist 
 
S a m pl e siz e:  
B as e d o n r es ults fr o m t h e P h as e 2 st u dy, it is ass u m e d t h at t h e  a v er a g e tr e at m e nt diff er e nc e 
b et w e e n S P N -8 1 0 d os e gr o u ps a n d pl ac e b o is  1 1. 5 1 wit h a c o m m o n st a n d ar d d e vi ati o n of 2 7. 3. A 
s a m pl e siz e of 1 3 2  s u bj ects p er ar m (2 6 4  s u bj ects f or 3 ar ms) will yi el d 9 0 % p o w er t o d et ect a n o n-
z er o diff er e nc e b et w e e n t h e m e di a n of 1 8 m g or 3 6 m g d os e gr o u p a n d t h e pl ac e b o usi n g t h e 
Wilc ox o n r a nk -s u m t est wit h a 2-si d e d si g nific a nc e l e v el al p h a = 0. 0 5.  
It is ass u m e d t h at a p pr oxi m at el y 2 0 % of s u bj ects will dr o p o ut b ef or e t h e c o m pl eti o n of t h e st u dy 
a n d h e nc e, a n a dj ust e d t ot al of 3 3 0  s u bj ects will b e r a n d o miz e d i n a 1: 1: 1 r ati o t o o bt ai n 26 4  
s u bj ects i n t h e I T T p o p ul ati o n at t h e c o m pl eti o n of t h e st u dy.   
T h e s a m pl e siz e w as c alc ul at e d usi n g t h e n Q u er y A dvis or S oft w ar e, V ersi o n 7.    

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
A n al ysis P o p ul ati o ns:  
S af et y P o p ul ati o n :  will i n cl u d e all r a n d o miz e d s u bj ects w h o r ec ei v e d at l e ast 1 d os e of st u dy dr u g.  
I nt e nt-t o-Tr e at (I T T) P o p ul ati o n :  will i ncl u d e all s u bj ects w h o r ec eiv e d at l e ast 1 d os e of st u dy dr u g 
a n d h a v e a b as eli n e a n d at l e ast 1 v ali d p ost -r a n d o miz ati o n ass ess m e nt of fr e q u e nc y of I A  
b e h a vi ors b as e d o n I A  di ary e ntry.  
P er -Pr ot oc ol ( P P) P o p ul ati o n :  will i ncl u d e all of t h e s u bj ects i n t h e I T T p o p ul ati o n w h o c o m pl et e d 
t h e tr e at m e nt p eri o d wit h 8 0 % di ary c o m pl eti o n c o m pli a nc e a n d w h o di d n ot h av e m aj or pr ot oc ol 
d e vi ati o ns.  
P K p o p ul ati o n :  will i ncl u d e all s u bj ects i n t h e s af et y p o p ul ati o n w h o h a d at l e ast o n e P K s a m pl e 
dr a w n w hic h h a d a q u a ntit at a bl e c o nc e ntr ati o n f or at l e ast o n e a n alyt e of i nt er est . 
H y p ot h es es:  
L et 1, 2, a n d 3 r e pr es e nt t h e m e di a n p erc e nt c h a n g e i n t h e fr e q u e ncy of I A b e h a vi ors p er 7 d a ys 
i n t h e Tr e at m e nt  p eri o d r el ati v e t o t h e B as eli n e  p eri o d i n t h e I T T p o p ul ati o n f or s u bj ect s tr e at e d 
wit h Pl ac e b o, 1 8 m g a n d 3 6 m g d os e s of S P N -8 1 0 , r es p ecti v el y.  T h e n ull ( H 0) a n d t h e alt er n ativ e 
( Ha) hy p ot h es es ar e as i n t h e f oll o wi n g. 
 
H 0 1: 2= 1, (t h er e is n o diff er e nc e b et w e e n t h e m e di a n of t h e 1 8 m g d os e S P N -8 1 0  a n d t h e 
m e di a n of pl ac e b o) vs. H
a 1: 2≠ 1,(t h er e is a diff er e nc e b et w e e n t h e m e di a n of t h e 1 8 m g 
d os e S P N -8 1 0   a n d t h e m e di a n of pl ac e b o)  
 
H 0 2: 3= 1, (t h er e is n o diff er e nc e b et w e e n t h e m e di a n of t h e 3 6 m g d os e S P N -8 1 0  a n d t h e 
m e di a n of pl ac e b o) vs. H
a 2: 3≠ 1,(t h er e is a diff er e nc e b et w e e n t h e m e di a n of t h e 3 6 m g 
d os e  S P N -8 1 0   a n d t h e m e di a n of pl ac e b o)  
H a n dli n g Missi n g D at a:  
F or t h e pri m ary effic acy e n d p oi nt, t h e fr e q u e ncy of I A b e h a vi ors d uri n g t h e tr e at m e nt p eri o d will 
b e c alc ul at e d ov er t h e n u m b er of d ays wit h n o n -missi n g I A di ary d at a i n t h e tr e at m e nt p eri o d. N o 
ex plicit i m p ut ati o n of missi n g d at a will b e us e d, b ut t his a p pr o ac h is i m plicitl y e q ui v al e nt t o usi n g 
t h e fr e q u e ncy of I A b e h avi ors d uri n g t h e d a ys wit h n o n-missi n g I A di ary d at a t o i m p ut e t h e 
fr e q u e nc y f or d ays aft er st u dy disc o nti n u ati o n a n d d ays wit h missi n g I A di ary d at a.  
P h ar m ac o ki n etic M et h o ds:  
S a m pli n g : 
5  bl o o d s a m pl e s di vi d e d b et w e e n 2  visits.  
Bi o a n al ytic al A n al ysis:  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 
 
P h ar m ac oki n etic  A n al ysis:  
  
 
 
 
   
 
 
 
St atistic al M et h o ds:  
S u m m ari es f or c o nti n u o us v ari a bl es will i ncl u d e t h e s a m pl e siz e, m e a n, a n d st a n d ar d d e vi ati o n, 
m e di a n, mi ni m u m, a n d m axi m u m. S u m m ari es f or discr et e v ari a bl es  w ill i ncl u d e t h e t a b ul ati o n of 
fr e q u e nci es a n d p erc e nt a g es.  
T h e pri m ar y effic acy a n alysis will b e b as e d o n t h e I T T p o p ul ati o n.  T h e pri m ar y effic ac y e n d p oi n t is 
t h e p erc e nt c h a n g e i n t h e fr e q u e nc y  ( u n w ei g ht e d sc or e) of I A b e h avi ors p er  7 d ays i n t h e 
Tr e at m e nt  p eri o d r el ati v e t o t h e B as eli n e  p eri o d i n t h e I T T p o p ul ati o n c alc ul at e d ov er t h e n u m b er 
of d a ys wit h n o n -missi n g I A di ar y d at a.  
T h e pri m ar y effic acy a n alysis will b e p erf or m e d usi n g t h e Wilc ox o n r a n k -s u m t est t o c o m p ar e t h e 
m e di a ns of e ac h of t h e t w o d os es of S P N -8 1 0 ( 1 8 m g a n d 3 6 m g) wit h t h e m e di a n of t h e Pl ac e b o.  
T h e H o d g es -L e h m a n n esti m at e a n d t h e ass oci at e d 9 5 % c o nfi d e nc e i nt erv al ( CI) will b e c al c ul at e d. 
T h e r o b ust n ess of t h e pri m ar y a n al ys es will b e c h ec k e d b y p erf or mi n g t w o s e nsitivit y a n al ys es .   
E ac h o n e of t h e  six s ec o n d ar y e n d p oi nts will b e a n alyz e d usi n g t h e a n al ysis of c ov ari a nc e m et h o d 
b as e d o n t h e I T T p o p ul ati o n wit h missi n g d at a i m p ut e d usi n g t h e L ast O bs er v ati o n C arri e d F or w ar d 
(L O C F) m et h o d. T h e m o d el i ncl u d es tr e at m e nt a n d b as eli n e as fix e d i n d e p e n d e nt c o v ari at es a n d 
c h a n g e fr o m b as eli n e t o fi n al m ai nt e n a nc e visit as a r es p o ns e v ari a bl e. T h e l e ast s q u ar es m e a n of 
e ac h tr e at m e nt gr o u p, t h e diff er e nc e i n t h e  l e ast s q u ar es m e a n ( 1 8 m g d os e mi n us pl ac e b o a n d 3 6 
m g d os e mi n us pl ac e b o), a n d t h e 2 -si d e d 9 5 % CI f or t h e diff er e nc e will b e o bt ai n e d.   
I nt eri m a n al ysis: 
A si n gl e i nt eri m a n alysis will b e p erf or m e d aft er a p pr oxi m at el y 5 0 % of t h e r a n d o miz e d s u bj ects 
c o m pl et e t h e st u dy. T h e m ai n p ur p os e of t h e i nt eri m a n al ysis is t o r e-esti m at e t h e s a m pl e siz e .  
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S af et y a n a l ysis: 
S af et y  a n al ys es  will b e b as e d o n t h e s af et y p o p ul ati o n.   All A Es will b e c o d e d usi n g t h e M e dic al 
Dicti o n ar y f or R e g ul at or y Acti viti es ( M e d D R A) a n d will b e s u m m ariz e d usi n g discr et e s u m m ari es at 
t h e s u bj ect a n d ev e nt l ev el b y syst e m or g a n cl ass a n d pr ef err e d t er m f or e ac h tr e at m e nt gr o u p.  
Si mil arly, tr e at m e nt -e m er g e nt A Es will b e s u m m ariz e d b y s ev erit y a n d r el ati o ns hi p s e p ar at ely.  
Vit al si g ns will b e s u m m ariz e d usi n g d escri ptiv e st atistics by tr e at m e nt gr o u ps.  T h e s u m m ary 
i ncl u d es s a m pl e siz e, m e a n, a n d st a n d ar d d evi ati o n, m e di a n, mi ni m u m, a n d m axi m u m.  C o nti n u o us 
l a b or at or y p ar a m et ers will b e s u m m ariz e d si mil arly.  If a p plic a bl e, c at e g oric al l a b or at or y t ests will 
b e s u m m ariz e d usi n g n u m b er a n d p erc e nt of s u bj ects b y tr e at m e nt gr o u ps.   D at a o n i nfr e q u e nt 
b e h a vi ors will b e list e d.  
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T A BL E O F C O N T E N T S  
 
TI TL E P A G E ............................................................................................................................ 1 
S U M M A R Y O F C H A N G E S ........................................................................................................ 4 
CLI NI C AL P R O T O C OL S Y N O P SI S ............................................................................................ 1 8  
T A BL E O F C O N T E N T S ........................................................................................................... 2 4  
LI S T O F T A BL E S A N D FI G U R E S .............................................................................................. 2 8  
LI S T O F A B B R E VI A TI O N S ...................................................................................................... 2 9  
1  
I N T R O D U C TI O N ............................................................................................................ 3 1  
1. 1  
B ac k gr o u n d ................................................................................................................... 3 1  
1. 2  
S p o ns or’s P h as e 2 a St u d y  ............................................................................................... 3 2  
1. 3  
S p o ns or’s P h as e 2 b St u d y  ............................................................................................... 3 3  
1. 4  
I m p ulsi v e A g gr essi o n Di ar y (I A Di ar y) ............................................................................. 3 4  
1. 5  
St u d y R ati o n al e ............................................................................................................. 3 4  
2  
S T U D Y O BJ E C TI V E S ....................................................................................................... 3 4  
2. 1  
Pri m ar y O bj ecti v e .......................................................................................................... 3 4  
2. 2  
S e c o n d ar y O bj ecti v es ..................................................................................................... 3 5  
2. 3  
T erti ar y O bj ecti v e .......................................................................................................... 3 5  
3  
I N V E S TI G A TI O N AL PL A N ............................................................................................... 3 5  
3. 1  
R a ti o n al e f or St u d y D esi g n, I ncl u di n g C h oic e of Tr e at m e nt Gr o u ps, A p pr o pri at e n ess of 
M e as ur e m e nts ............................................................................................................................. 3 5  
3. 2  
O v er all St u d y D esi g n a n d Pl a n ........................................................................................ 3 6  
3. 2. 1  
Pr e- Tr e at m e nt P h as e .......................................................................................................... 3 6  
3. 2. 1. 1  
Scr e e ni n g P eri o d ........................................................................................................................... 3 6  
3. 2. 1. 2  
B as eli n e P eri o d .............................................................................................................................. 3 7  
3. 2. 2  
Tr e at m e nt P h as e ................................................................................................................. 3 8  
3. 2. 2. 1  
R a n d o miz ati o n .............................................................................................................................. 3 8  
3. 2. 2. 2  
Titr ati o n P eri o d ............................................................................................................................. 3 8  
3. 2. 2. 3  
M ai nt e n a nc e P eri o d ...................................................................................................................... 3 8  
3. 2. 3  
C o nv ersi o n/ T a p er P h as e ..................................................................................................... 3 8  
3. 2. 4  
E n d of St u dy / E arly T er mi n ati o n ........................................................................................ 3 8  
4  
S T U D Y M E T H O D S .......................................................................................................... 4 1  
4. 1  
S el ecti o n of St u d y P o p ul ati o n ......................................................................................... 4 1  
4. 1. 1  
I ncl usi o n Crit eri a ................................................................................................................. 4 1  
4. 1. 2  
Excl usi o n Crit eri a ................................................................................................................. 4 1  
4. 2  
Sc h e d ul e of Visits a n d Pr oc e d ur es .................................................................................. 4 2  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4. 2. 1  
Visit 1 ................................................................................................................................... 4 5  
4. 2. 2  
Visit 2 ................................................................................................................................... 4 5  
4. 2. 3  
Visit 3 ................................................................................................................................... 4 5  
4. 2. 4  
Visit 4 ................................................................................................................................... 4 6  
4. 2. 5  
Visit 5 ................................................................................................................................... 4 6  
4. 2. 6  
Visit 6 ................................................................................................................................... 4 7  
4. 2. 7  
Visit 7 ................................................................................................................................... 4 7  
4. 2. 8  
P h ar m ac o ki n etic S a m pl e C oll ecti o n .................................................................................... 4 8  
4. 3  
Tr e at m e nts .................................................................................................................... 4 8  
4. 3. 1  
Tr e at m e nts A d mi nist er e d ................................................................................................... 4 8  
4. 3. 2  
I d e ntit y of I nv esti g ati o n al Pr o d uct(s) ................................................................................. 4 8  
4. 3. 3  
St u dy M e dic ati o n H a n dli n g a n d Acc o u nt a bility .................................................................. 4 9  
4. 3. 4  
M et h o d of Assi g ni n g S u bj ects t o Tr e at m e nt Gr o u ps .......................................................... 4 9  
4. 3. 5  
Tr e at m e nt R e pl ac e m e nt ..................................................................................................... 5 0  
4. 3. 6  
D osi n g Sc h e d ul e .................................................................................................................. 5 0  
4. 3. 7  
M et h o d of A d mi nistr ati o n .................................................................................................. 5 0  
4. 3. 8  
Bli n di n g ............................................................................................................................... 5 0  
4. 4  
Pr o hi bit e d M e dic ati o ns: ................................................................................................. 5 1  
4. 5  
C o nc o mit a nt M e dic ati o n ................................................................................................ 5 1  
4. 6  
C o m pl eti o n of St u d y a n d Disc o nti n u ati o n of S u bj ects ..................................................... 5 2  
5  
A N AL Y SI S V A RI A BL E S .................................................................................................... 5 2  
5. 1  
Pri m ar y Effic ac y V ari a bl e ................................................................................................ 5 2  
5. 2  
S ec o n d ar y Effic ac y V ari a bl es .......................................................................................... 5 3  
5. 2. 1  
Cli nic al Gl o b al I m pr essi o n ( C GI) Sc al es ............................................................................... 5 3  
5. 2. 2  
S w a ns o n, N ol a n, P el h a m R ati n g Sc al e- R e vis e d ( S N A P- I V) ................................................. 5 3  
5. 2. 3  
C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8- It e m ( C H Q- P F 2 8) ......................................... 5 4  
5. 2. 4  
P ar e nti n g Str ess I n d ex- S h ort F or m ( P SI- 4- S F)  ..................................................................... 5 4  
5. 3  
P h ar m ac o ki n etic M e as ur e m e nts .................................................................................... 5 4  
5. 3. 1  
P h ar m ac o ki n etic V ari a bl es .................................................................................................. 5 4  
5. 3. 2  
Ex pl or at ory P h ar m ac o ki n etic V ari a bl es .............................................................................. 5 4  
5. 4  
S af et y Ass ess m e nts ........................................................................................................ 5 5  
5. 4. 1  
A dv ers e E v e nts .................................................................................................................... 5 5  
5. 4. 1. 1  
C a us alit y ........................................................................................................................................ 5 5  
5. 4. 1. 2  
R ec or di n g a n d E v al u ati o n of A d v ers e E v e nts ................................................................................ 5 5  
5. 4. 1. 3  
Crit eri a f or Ass essi n g S e v erit y ....................................................................................................... 5 6  
5. 4. 1. 4  
Crit eri a f or Ass essi n g C a us alit y ..................................................................................................... 5 6  
5. 4. 2  
S eri o us A dv ers e Ev e nts ( S A E) .............................................................................................. 5 7  
5. 4. 2. 1  
I n v esti g at or R es p o nsi biliti es f or R e p orti n g S A Es .......................................................................... 5 7  
5. 4. 2. 2  
Ot h er E v e nts R e q uiri n g I m m e di at e R e p orti n g .............................................................................. 5 8  
5. 4. 2. 3  
S p o ns or R es p o nsi biliti es f or Ex p e dit e d R e p orti n g of S A Es ........................................................... 5 9  
5. 4. 3 
M a n a g e m e nt of Tr e at m e nt- E m er gi n g E P S ......................................................................... 5 9  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
5. 4. 4  
L a b or at ory M e as ur e m e nts ................................................................................................. 5 9  
5. 4. 5  
Vit al Si g n a n d H ei g ht/ W ei g ht M e as ur e m e nts .................................................................... 6 0  
5. 4. 6  
M e dic al Hist ory ................................................................................................................... 6 0  
5. 4. 7  
P hysic al Ex a mi n ati o ns a n d El ectr oc ar di o gr a ms ( E C Gs) ...................................................... 6 0  
5. 4. 8  
Ot h er S p eci al T ests .............................................................................................................. 6 1  
5. 4. 8. 1  
K- S A D S- PL 2 0 1 3 Di a g n ostic I nt er vi e w ........................................................................................... 6 1  
5. 4. 8. 2  
Si m ps o n- A n g us Sc al e .................................................................................................................... 6 1  
5. 4. 8. 3  
B ar n es A k at hisi a Sc al e ................................................................................................................... 6 1  
5. 4. 8. 4  
A b n or m al I n v ol u nt ar y M o v e m e nt Sc al e ( AI M S) ........................................................................... 6 1  
5. 4. 8. 5  
Viti ell o A g gr essi o n Sc al e ............................................................................................................... 6 2  
5. 4. 8. 6  
R etr os p ecti v e- M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S) .......................................................... 6 2  
5. 4. 8. 7  
C ol u m bi a S uici d e S e v erit y R ati n g Sc al e ( C- S S R S) .......................................................................... 6 2  
5. 4. 8. 8  
I nfr e q u e nt B e h a vi ors C h ec klist ..................................................................................................... 6 2  
6  
S T A TI S TI C AL M E T H O D S ................................................................................................. 6 2  
6. 1  
St atistic al a n d A n al ytic al Pl a ns ....................................................................................... 6 2  
6. 2  
H a n dli n g Missi n g D at a ................................................................................................... 6 3  
6. 3  
A n al ysis P o p ul ati o ns ...................................................................................................... 6 3  
6. 4  
D e m o gr a p hic a n d B as eli n e C h ar act eristics ...................................................................... 6 4  
6. 5  
S u bj ect Dis p ositi o n ........................................................................................................ 6 4  
6. 6  
Pr ot oc ol D e vi ati o ns ........................................................................................................ 6 4 
6. 7  
St u d y M e dic ati o n E x p os ur e a n d C o m pli a nc e ................................................................... 6 5  
6. 8  
C o nc o mit a nt M e dic ati o ns .............................................................................................. 6 5  
6. 9  
Effic ac y A n al ys es ............................................................................................................ 6 5  
6. 9. 1  
Pri m ar y Effic acy A n al ysis ..................................................................................................... 6 5  
6. 9. 2  
S ec o n d ar y Effic ac y A n alys es ............................................................................................... 6 6  
6. 9. 3  
S e nsiti vity A n al ysis .............................................................................................................. 6 7  
6. 9. 3. 1  
M ulti pl e i m p ut ati o n u n d er  Missi n g at R a n d o m ( M A R) ................................................................ 6 7  
6. 9. 3. 2  
M ulti pl e i m p ut ati o n u n d er Missi n g N ot at R a n d o m ( M N A R) ....................................................... 6 8  
6. 9. 3. 3  
P er Pr ot oc ol A n al ysis ..................................................................................................................... 6 8  
6. 1 0  
S a m pl e Siz e a n d P o w er C o nsi d er ati o ns ........................................................................... 6 8  
6. 1 1  
I nt eri m A n al ysis ............................................................................................................. 6 8  
6. 1 2  
Ass ess m e nt of M CI C ....................................................................................................... 6 8  
6. 1 3  
P h ar m ac o ki n etic A n al ys es .............................................................................................. 7 0  
6. 1 4  
S af et y A n al ys es .............................................................................................................. 7 0  
6. 1 4. 1  
A dv ers e E v e nts .................................................................................................................... 7 0  
6. 1 4. 2  
L a b or at ory V al u es ............................................................................................................... 7 1  
6. 1 4 . 3  
Vit al Si g ns, H ei g ht a n d W ei g ht ............................................................................................ 7 1  
6. 1 4. 4  
E C G R es ults ......................................................................................................................... 7 1  
6. 1 4. 5  
P hysic al Ex a mi n ati o ns ......................................................................................................... 7 2  
6. 1 4. 6  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( C- S S R S) ................................................................ 7 2  
6. 1 4. 7  
I nfr e q u e nt B e h avi ors C h ecklist ........................................................................................... 7 2  
6. 1 4. 8  
Ot h er S p eci al T ests .............................................................................................................. 7 2  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
7  
D O C U M E N T A TI O N ........................................................................................................ 7 2  
7. 1  
A d h er e nc e t o t h e Pr ot oc ol ............................................................................................. 7 2  
7. 2  
C h a n g es t o t h e Pr ot oc ol ................................................................................................. 7 2  
7. 3  
Pr ot oc ol D e vi ati o ns ........................................................................................................ 7 3  
7. 4  
D at a Q u alit y Ass ur a nc e .................................................................................................. 7 3  
7. 4. 1  
D at a C oll ecti o n .................................................................................................................... 7 3  
7. 4. 2  
Cli nic al D at a M a n a g e m e nt .................................................................................................. 7 4  
7. 4. 3  
D at a b as e Q u ality Ass ur a nc e ............................................................................................... 7 4  
7. 4. 4  
Bi o a n al ytic al D at a M a n a g e m e nt a n d Q u ality C o ntr ol ........................................................ 7 4  
7. 5  
R et e nti o n of R ec or ds ..................................................................................................... 7 4  
7. 6  
A u diti n g Pr oc e d ur es ....................................................................................................... 7 5  
7. 7  
P u blic ati o n of R es ults ..................................................................................................... 7 5  
7. 8  
Fi n a nci n g a n d I ns ur a nc e ................................................................................................. 7 5  
7. 9  
Discl os ur e a n d C o nfi d e nti alit y ........................................................................................ 7 5  
7. 1 0  
Disc o nti n u ati o n of St u d y ................................................................................................ 7 6  
8  
E T HI C S .......................................................................................................................... 7 6  
8. 1  
I nstit uti o n al R e vi e w B o ar ds / I n d e p e n d e nt Et hics C o m mitt e es ........................................ 7 6  
8. 2  
Et hic al C o n d uct of t h e St u d y ........................................................................................... 7 6  
8. 3  
I n v esti g at ors a n d St u d y P ers o n n el .................................................................................. 7 7  
8. 4  
S u bj ect I nf or m ati o n a n d C o ns e nt/ Ass e nt ........................................................................ 7 7  
9  
R E F E R E N C E LI S T ............................................................................................................ 7 7  
1 0  
A P P E N DI C E S .............................................................................................................. 8 1  
1 0. 1  
A d a pti v e D esi g n Pl a n ..................................................................................................... 8 1  
1 0 . 1. 1  
I ntr o d ucti o n ........................................................................................................................ 8 1  
1 0. 1. 2  
Tri al D esi g n .......................................................................................................................... 8 1  
1 0. 1. 3  
D ecisi o n R ul es at I nt eri m A n al ysis ...................................................................................... 8 2  
1 0. 1. 4  
A d a pti v e D esi g n .................................................................................................................. 8 3  
1 0. 1. 5  
I m p ort a nt I nt eri m A n alysis C o nsi d er ati o ns ........................................................................ 8 6  
1 0. 1. 5. 1  R es p o nsi bl e P art y .......................................................................................................................... 8 6  
1 0. 1. 5. 2  C o nfi d e nti alit y ............................................................................................................................... 8 6  
1 0. 2  
R etr os p ecti v e M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S) .............................................. 8 7  
1 0. 3  
Cli nic al Gl o b al I m pr essi o n ( C GI) Sc al e ............................................................................. 8 9  
1 0. 4  
Viti ell o Sc al e .................................................................................................................. 9 0  
1 0 . 5 
Ki d di e- S a ds- Pr es e nt a n d Lif eti m e V ersi o n ( K- S A D S- PL) 2 0 1 3 ............................................ 9 1  
1 0. 6  
C ol u m bi a- S uici d e S e v erit y R ati n g Sc al es ( C- S S R S) .......................................................... 2 0 2 
1 0. 7  
S w a ns o n, N ol a n a n d P el h a m R ati n g Sc al e- R e vis e d ( S N A P I V) ......................................... 2 0 9 
1 0. 8  
Si m ps o n- A n g us R ati n g Sc al e ......................................................................................... 2 1 0 
1 0. 9  
B ar n es A k at hisi a R ati n g Sc al e ( B A R S) ............................................................................ 2 1 4 
1 0. 1 0  
A b n or m al I n v ol u nt ar y M o v e m e nt Sc al e ( AI M S) ............................................................ 2 1 6 
1 0. 1 1  
C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8-it e m ( C H Q- P F 2 8) ........................................ 2 2 1 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1 2  
P ar e nti n g Str ess I n d e x- S h ort F or m ( P SI- 4- S F) ................................................................ 2 2 5 
 
LI S T O F T A BL E S A N D FI G U R E S 
 
T a bl e 1:  Sc h e d ul e of Visits a n d Pr oc e d ur es ............................................................................................... 4 3  
T a bl e 2: D osi n g Sc h e d ul e ( T ot al D aily D os e) ............................................................................................... 5 0  
T a bl e 3: Cli nic al L a b or at or y T ests ............................................................................................................... 6 0  
 
Fi g ur e 1: Tr e at m e nt Sc h e d ul e ( C o nv ersi o n) ............................................................................................... 3 9  
Fi g ur e 2: Tr e at m e nt Sc h e d ul e ( T a p er) ........................................................................................................ 4 0  
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
LI S T O F A B B R E VI A TI O N S 
 
A D H D  
Att e nti o n -D eficit Hy p er activit y Dis or d er  
A E  
A dv ers e E v e nt  
A E SI  
A dv ers e E v e nt of S p eci al I nt er est  
AI M S  
A b n or m al I nv ol u nt ary M o v e m e nt Sc al e  
A S D  
A utis m S p ectr u m Dis or d er  
BI D  
T wic e a D a y  
C F R  
C o d e of F e d er al R e g ul ati o ns  
C GI -S  
Cli nic al Gl o b al I m pr essi o n –  S e v erit y of Ill n ess  
C GI -I 
Cli nic al Gl o b al I m pr essi o n –  Gl o b al I m pr ov e m e nt  
C H Q -P F 2 8  
CL/ F  
C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8 -it e m  
A p p ar e nt Cl e ar a nc e  
C R A  
Cli nic al R es e arc h Ass oci at e  
C R O  
C o ntr act R es e arc h Or g a niz ati o n  
C -S S R S  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e  
e C R F  
El ectr o nic C as e R e p ort F or m  
E P S  
Extr a pyr a mi d al Sy m pt o ms  
F O C B P  
F e m al es of C hil d b e ari n g P ot e nti al  
I A 
I m p ulsiv e A g gr essi o n  
I A F 
I nf or m e d A ss e nt F or m  
I C F 
I nf or m e d C o ns e nt For m  
I C H 
I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n 
I E C 
I n d e p e n d e nt Et hics C o m mitt e e 
I R B 
I nstit uti o n al R evi e w B o ar d 
I T T 
I nt e nt t o Tr e at 
K BI T -2  
K a uf m a n Bri ef I nt elli g e nc e T est, S ec o n d E diti o n  
K -S A D S -PL  2 0 1 3  
Sc h e d ul e f or Aff ecti v e Dis or d ers a n d Sc hiz o p hr e ni a f or Sc h o ol -a g e d 
C hil dr e n –  Pr es e nt a n d Lif eti m e V ersi o ns  2 0 1 3  
L S M 
L e ast-s q u ar e M e a ns  
M A R  
Missi n g at R a n d o m  
M e d D R A  
M e dic al Dicti o n ary f or R e g ul at or y Activiti es  
MI  
M ulti pl e I m p ut ati o n  
M N A R  
Missi n g  N ot at R a n d o m  
O D D  
O p p ositi o n al D efi a nt Dis or d er  
P K  
P SI -4 -S F 
P h ar m ac o ki n etic(s)  
P ar e nti n g Str ess I n d ex –  S h ort F or m  
Q D  
O nc e a D ay  
R -M O A S  
R etr os p ectiv e M o difi e d O v ert A g gr essi o n Sc al e  
S A E  
S eri o us A dv ers e E v e nt 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S A P  
St atistic al A n alysis Pl a n  
S M  
St u dy M e dic ati o n  
S N A P -I V 
S w a ns o n, N ol a n a n d P el h a m R ati n g Sc al e - R evis e d  
T D D  
T ot al D aily D os e  
UL N  
U p p er Li mit of N or m al  
V/ F  
A p p ar e nt V ol u m e of Distri b uti o n  
   
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1  I N T R O D U C TI O N 
1. 1  B ac k gr o u n d 
B e h a vi or wit h t h e i m m e di at e i nt e nt t o c a us e h ar m –  w h et h er t o s elf, ot h ers, o bj ects, or pr o p ert y –  
c o nstit ut es a g gr essi o n. A g gr essi v e b e h avi or b ec o m es m al a d a ptiv e w h e n it p ersists, occ urs o utsi d e a n 
acc e pt a bl e s oci al c o nt ext, a n d is of a n i nt e nsity, fr e q u e nc y, s e v erity a n d/ or d ur ati o n d etri m e nt al t o t h e 
c hil d’s i nt er ests ( C o n n or 2 0 0 6; J e ns e n 2 0 0 7). M al a d a pti v e a g gr essi o n is a n ex pr essi o n of c e ntr al n erv o us 
s yst e m d ysf u ncti o n a n d m ay t h er ef or e b e a m e n a bl e t o tr e at m e nts t ar g eti n g its n e ur o bi ol o gic s u bstr at e.  
A g gr essi o n c a n b e c at e g oriz e d i nt o t w o br o a d s u bt y p es b as e d o n t h e a g gr e ss or’s m otiv ati o n – 1) 
r e activ e or i m p ulsiv e a n d 2) pr o acti v e or i nstr u m e nt al ( Viti ell o 1 9 9 7). I m p ulsiv e a g gr essi o n (I A) is a n gr y, 
r et ali at or y a g gr essi o n arisi n g o ut of fr ustr ati o n, a n n oy a nc e, or h ostilit y t o r e al or p erc eiv e d pr o v oc ati o ns 
–  str ess ors t h at y o ut h of t h e s a m e a g e ty pic all y ex p eri e nc e wit h e q u a ni mit y. I A is t h er ef or e a n 
u n pl a n n e d a n d i m m e di at e r es p o ns e r efl ecti n g o ut- of -c o ntr ol e m oti o n alit y t h at s atisfi es i m m e di at e 
e m oti o n al pr ess ur es, al b eit wit h n e g ati v e c o ns e q u e nc es t o t h e a g gr ess or. I n c o ntr ast, i nstr u m e nt al 
a g gr essi o n is c o nsci o usly pl a n n e d, g o al- ori e nt e d b e h avi or wit h t h e s p ecific i nt e nt of b e n efiti n g t h e 
a g gr ess or (J e ns e n 2 0 0 7).   
I A is a c o m m o n c o m or bi dity i n att e nti o n- d eficit/ h y p er acti vity dis or d er ( A D H D) a n d is oft e n r efr act or y t o 
pri m ar y A D H D t h er a py. I n t h e M ulti m o d al Tr e at m e nt of C hil dr e n wit h A D H D ( M T A) st u dy ( M T A 1 9 9 9), 
5 4 % of pr e a d ol esc e nt st u dy p artici p a nts wit h A D H D C o m bi n e d s u bt y p e dis pl a y e d cli nic all y si g nific a nt 
a g gr essi o n at b as eli n e. Of t h es e, 4 4 % r e m ai n e d si g nific a ntl y sy m pt o m atic i n t er ms of a g gr essi v e 
b e h a vi or aft er 1 4 m o nt hs of o pti m al m e dic ati o n (sti m ul a nts) wit h/ wit h o ut b e h a vi or al t h er a py (J e ns e n, 
2 0 0 7).  
I A a m plifi es t h e psyc h ol o gic al, ac a d e mic, e m oti o n al, a n d s oci al pr o bl e ms ass oci at e d wit h A D H D 
( S h elt o n, 1 9 9 8), m ar k e dly i ncr e asi n g t h e ris k of p e rsist e nt b e h avi or al pr o bl e ms, c o n d uct dis or d er, 
e nc o u nt ers wit h t h e j ustic e s yst e m, d eficits i n ac a d e mic ac hi ev e m e nt, b e h avi or al a n d disci pli n ar y 
pr o bl e ms at sc h o ol, a n d s u bst a nc e ex p eri m e nt ati o n/ a b us e. E arly- o ns et, p erv asi v e a n d u nr e mitti n g I A i n 
t h e c o nt ext of i m p ulsiv e t h o u g hts, e m oti o n al l a bilit y, a n d i m p ulsiv e b e h avi or is t h o u g ht t o r e pr es e nt a 
hi g h-ris k pr ofil e f or pr o gr essi o n fr o m c hil d h o o d A D H D t o a d ult a ntis oci al dis or d ers ( Mc K a y, 2 0 0 1). I n t h e 
c o nt ext of A D H D it r e pr es e nts a s eri o us cli nic al a n d p u blic h e alt h c o nc er n a n d w arr a nts eff ectiv e a n d 
ti m ely i nt er v e nti o n. 
Si nc e pri m ary A D H D t h er a py h as li mit e d eff ect o n I A, a st e p p e d-c ar e a p pr o ac h h as b e e n r ec o m m e n d e d, 
wit h a g gr essi o n-t ar g et e d t h er a py s uc h as a n a nti psyc h otic a d d e d t o A D H D t h er a py t o m a n a g e r esi d u al 
a g gr essi v e b e h avi ors ( Sc ott o- R os at o 2 0 1 2). R is p eri d o n e a n d ot h er “ aty pic al” a nti ps yc h otics h av e 
hist oric ally b e e n at t h e f or efr o nt of tr e at m e nt r ec o m m e n d ati o ns r e g ar di n g c o m bi n ati o n t h er a py f or 
m a n a gi n g c o m or bi d a g gr essi o n i n c hil dr e n wit h A D H D ( P a p p a d o p ul os et al. 2 0 0 3; Plisz k a et al. 2 0 0 6; 
Plisz k a et al. 2 0 0 7). H o w ev er, o nly t w o d o u bl e- bli n d r a n d o miz e d pl ac e b o-c o ntr oll e d tri als of ris p eri d o n e 
as a dj u ncti v e t h er a py i n c hil dr e n wit h A D H D a n d a g gr essi o n r efr act or y t o sti m ul a nts h a v e b e e n 
p u blis h e d –  1) a pil ot st u dy i n 2 5 c hil dr e n t h at w as li k el y u n d er p o w er e d a n d di d n ot d et ect a si g nific a nt 
tr e at m e nt eff ect ( Ar m e nt er os 2 0 0 7; A m a n 2 0 1 4) a n d 2) t h e r ec e ntl y c o m pl et e d T O S C A ( Tr e at m e nt of 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S e v er e C hil d h o o d A g gr essi o n) st u dy ( F ar m er et al. 2 0 1 1; A m a n 2 0 1 4; G a d o w 2 0 1 4). T h e eff ect siz e f or 
ris p eri do n e’s eff ect o n I A w as s m all ( 0. 2 9), ev e n t h o u g h t h e d os a g e c o ul d b e a dj ust e d t o o pti m al eff ect. 
T h e T O S C A st u dy pr ovi d es i niti al e m piric al evi d e nc e s u p p orti n g a st e p p e d-c ar e a p pr o ac h i n w hic h A D H D 
c hil dr e n wit h s e v er e a g gr essi o n ar e i niti ally tr e at e d wit h pri m ar y A D H D t h er a py f oll o w e d b y a dj u nctiv e 
a nti ps yc h otic t h er a py t ar g et e d t o I A .  H o w e v er, t h e l o n g-t er m eff ects of ris p eri d o n e a n d si mil ar 
a nti ps yc h otics i n t er ms of m et a b olic d er a n g e m e nts pr e dicti v e of di a b et es a n d c ar di o v asc ul ar dis e as e, 
h a v e b ec o m e c a us e f or c o nsi d er a bl e c o nc er n, es p eci all y i n t h e f ac e of v er y li mit e d e vi d e nc e of effic ac y 
as a g gr essi o n-t ar g et e d t h er a py i n A D H D.   T h e T O S C A st u dy c o nfir m e d t h at sti m ul a nt c o-t h er a py d o es 
n ot att e n u at e t h e a d v ers e eff ects of ris p eri d o n e or si mil ar a g e nts o n b o dy c o m p ositi o n, m et a b olic 
p ar a m et ers, pr ol acti n, or s e d ati o n ( C al ar g e 2 0 0 9; P e nz n er 2 0 0 9). 
M oli n d o n e hy dr oc hl ori d e ( m oli n d o n e) is a m e di u m p ot e nc y a nti ps yc h otic, a n d is c urr e ntl y u n d er 
d e v el o p m e nt by t h e S p o ns or as a n ext e n d e d-r el e as e f or m ul ati o n ( S P N- 8 1 0), f or its p ot e nti al utilit y i n 
tr e ati n g I A i n c hil dr e n wit h A D H D.  
I n a n o p e n-l a b el st u dy, m oli n d o n e i m pr ov e d a g gr essi v e b e h a vi or i n c hil dr e n ( N = 6, 6- 1 1 y e ars of a g e) 
wit h u n d ers oci aliz e d c o n d uct dis or d er, a g gr essi v e ty p e ( Gr e e n hill 1 9 8 1).  T h e o pti m u m d os e w as 0. 5 
m g/k g/ d a y.  M oli n d o n e w as als o s h o w n t o b e eff ecti v e i n tr e ati n g a g gr essiv e b e h a vi or i n a d o u bl e- bli n d, 
8- w e e k, i n p ati e nt st u dy of 3 1  c hil dr e n, a g es 6 t o 1 1, wit h u n d ers oci aliz e d c o n d uct dis or d er, a g gr essiv e 
t y p e ( Gr e e n hill 1 9 8 5).  
Pri or t o its wit h dr a w al fr o m t h e U S m ar k et f or c o m m erci al r e as o ns, I m m e di at e- R el e as e M oli n d o n e 
( M o b a n ®) w as a p pr o v e d f or t h e tr e at m e nt of sc hiz o p hr e ni a i n a d ults a n d a d ol esc e nts. Its us e w as als o 
e v al u at e d i n a p e di atric p o p ul ati o n wit h e arly- o ns et sc hiz o p hr e ni a a n d sc hiz o aff ecti v e dis or d er w h e n it 
w as s el ect e d as t h e first- g e n er ati o n a nti ps yc h otic o n t h e b asis of its m or e f a v or a bl e s af ety pr ofil e f or 
c o m p aris o n wit h s ec o n d- g e n er ati o n a g e nts (ris p eri d o n e, ol a nz a pi n e) i n a n NI H-s p o ns or e d st u dy ( T E O S S, 
Tr e at m e nt of E a rl y- O ns et Sc hiz o p hr e ni a S p ectr u m Dis or d ers St u dy) ( Mc Cl ell a n 2 0 0 7). At a n a v er a g e 
d os e of 6 0 m g/ d a y (r a n g e, 1 0- 1 4 0 m g/ d ay), m oli n d o n e w as s h o w n t o b e s af e a n d w ell-t ol er at e d ( Sikic h 
2 0 0 8). M oli n d o n e ( 1 0- 1 4 0 m g/ d ay) w as n ot ass oci at e d wit h si g nific a nt i ncr e as es i n w ei g ht/ B MI (i n 
c o ntr ast t o ol a nz a pi n e). M oli n d o n e w as als o n ot ass oci at e d wit h m or e dyst o nic or p ar ki ns o ni a n 
s y m pt o ms w h e n giv e n wit h b e nztr o pi n e, alt h o u g h ak at hisi a w as r e p ort e d by m or e m oli n d o n e-tr e at e d 
s u bj ects. R es ults of r a n d o miz e d c o ntr oll e d tri als s uc h as T E O S S sti m ul at e d i nt er est i n t h e p ot e nti al 
us ef ul n ess of m oli n d o n e as a w ei g ht- a n d m et a b olic ally- n e utr al D 2-r ec e pt or a nt a g o nist i n c hil dr e n wit h 
A D H D a n d c o m or bi d I A. 
1. 2  S p o ns or’s P h as e 2 a St u d y  
St u dy 8 1 0 P 2 0 1, w as a pr o of- of -c o nc e pt, m ultic e nt er, o p e n-l a b el, p ar all el- gr o u p, r a n d o miz e d, d os e-
r a n gi n g, s af et y, a n d t ol er a bilit y st u dy of m oli n d o n e a d mi nist er e d as ex p eri m e nt al M oli n d o n e I m m e di at e 
R el e as e ( I R) c a ps ul es i n c hil dr e n wit h A D H D a n d p ersist e nt s eri o us c o n d uct pr o bl e ms ( St oc ks 2 0 1 2). 
T ar g et s u bj ects w er e h e alt hy m al e or f e m al e c hil dr e n a g e d 6 t o 1 2 y e ars, i ncl usiv e, wit h a di a g n osis of 
A D H D acc o m p a ni e d b y p ersist e nt s eri o us c o n d uct pr o bl e ms. A t ot al of 7 8 s u bj ects ( 1 9- 2 0 p er tr e at m e nt 
gr o u p) i n t e n U. S sit es w er e r a n d o miz e d. T h e pri m ar y o bj ecti v e w as t o e v al u at e t h e s af ety a n d 
t ol er a bility of f o ur w ei g ht- b as e d d os a g es of M oli n d o n e I R d os e d t hr e e ti m es d aily i n c hil dr e n wit h A D H D 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
a n d p ersist e nt s eri o us c o n d uct pr o bl e ms ( < 3 0 k g: 
/ d a y; ≥3 0 k g: 
 
m g/ d ay). T h e s ec o n d ary o bj ectiv es w er e t o 1) ex pl or e t h e r el ati o ns hi p b et w e e n m oli n d o n e pl as m a 
c o nc e ntr ati o n ex p os ur e a n d s af ety/t ol er a bilit y e n d p oi nts a n d 2) ass ess t h e eff ect of M oli n d o n e I R aft er 
6 w e e ks of m ai nt e n a nc e tr e at m e nt i n r e d uci n g p ersist e nt s eri o us c o n d uct pr o bl e ms as m e as ur e d b y t h e 
C o n d uct Pr o bl e m S u bsc al e of t h e Nis o n g er C hil d B e h avi or R ati n g F or m- T y pic al I nt elli g e nc e Q u oti e nt 
( N C B R F- TI Q). 
 
 
 
1. 3  S p o ns or’s P h as e 2 b St u d y 
S p o ns or c o m pl et e d a P h as e 2 b m ultic e nt er, r a n d o miz e d, d o u bl e- bli n d, pl ac e b o-c o ntr oll e d tri al i n t h e 
U nit e d St at es i n p e di atric s u bj ects 6 t o 1 2 y e ars of a g e di a g n os e d wit h A D H D a n d I A t h at w as n ot 
c o ntr oll e d b y o pti m al sti m ul a nt a n d b e h avi or al t h er a py ( S p o ns or St u dy 8 1 0 P 2 0 2).  T h e pri m ary o bj ectiv e 
of t h e st u dy w as t o ass ess t h e eff ect of a n ext e n d e d-r el e as e t a bl et f or m ul ati o n of m oli n d o n e 
hy dr oc hl ori d e ( S P N- 8 1 0) ( 1 2 t o 5 4 m g/ d a y) i n r e d uci n g I A as m e as ur e d b y t h e R etr os p ecti v e- M o difi e d 
O v ert A g gr essi o n Sc al e ( R- M O A S) aft er at l e ast t hr e e w e eks of assi g n e d tr e at m e nt. S ec o n d ary e n d p oi nts 
i ncl u d e d t h e r at e of r e missi o n of I A a n d m e as ur e m e nt of t h e eff ectiv e n ess of S P N- 8 1 0 o n Cli nic al Gl o b al 
I m pr essi o n ( C GI) a n d A D H D sc al es as w ell as ev al u ati o n of t h e s af et y a n d t ol er a bilit y of t h e 
dr u g.  P ati e nts w h o c o m pl et e d t h e st u dy w er e off er e d t h e o p p ort u nity t o c o nti n u e i nt o a n o p e n-l a b el 
p h as e of six m o nt hs d ur ati o n.   
S P N- 8 1 0 d os e wit hi n tr e at m e nt gr o u ps w as str atifi e d by w ei g ht ( b el o w/ a b ov e 2 0 k g).  B ot h t h e m e di u m 
( 2 4/ 3 6 m g) a n d l o w ( 1 2/ 1 8 m g) d os e gr o u ps s h o w e d st atistic ally si g nific a nt diff er e nc e fr o m t h e pl ac e b o 
gr o u p i n t h e c h a n g e fr o m b as eli n e t o Visit 1 0 i n R- M O A S b ut t h e hi g h ( 3 6/ 5 4 m g) d os e gr o u p w as n ot 
si g nific a ntl y diff er e nt fr o m t h e pl ac e b o gr o u p. F urt h er m or e, b ot h t h e l o w d os e a n d m e di u m d os e gr o u ps 
w er e si g nific a ntl y diff er e nt fr o m t h e hi g h d os e b as e d o n p air- wis e c o m p aris o n a m o n g t h e d os e gr o u ps.  
 
 
 
 
 
 
 
 
 
 
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 
 
  
1. 4  I m p ulsi v e A g gr essi o n Di ar y (I A Di ar y)  
S p o ns or h as d e v el o p e d a n d v ali d at e d a n e w m e as ur e m e nt t o ol t o ass ess b e h avi ors ass oci at e d wit h I A . 
T h e i m p ulsiv e a g gr essi o n di ar y ( I A di ary) is a n el ectr o nic o bs er v er-r e p ort e d o utc o m e ( e O bs R O) 
i nstr u m e nt t h at c o m pris es a n e pis o dic di ary (t o b e r e p ort e d as s o o n as p ossi bl e aft er t h e p ar e nt or ot h er 
g u ar di a n or o bs er v er wit n ess es t h e c hil d’s I A b e h a vi or) a n d a n ev e ni n g di ary (t o e n a bl e at a mi ni m u m, 
c o m pl eti o n of t h e di ar y o nc e e ac h d a y).  T h e I A di ary m o nit ors t h e fr e q u e ncy of occ urr e nc e of 1 5 IA 
b e h a vi ors: Y elli n g, Scr e a mi n g, T hr e at e ni n g, Scr atc hi n g, T hr o wi n g, Sl a m mi n g, Hitti n g S elf, Ar g ui n g, 
C ursi n g, N a m e C alli n g, S h ovi n g, H air P ulli n g, Fi g hti n g, Hitti n g Ot h ers, Kicki n g Ot h ers.  T h e d ev el o p m e nt 
pr oc ess f oll o w e d F D A’s “ G ui d a nc e f or I n d ustry P ati e nt - R e p ort e d O utc o m e M e as ur es: Us e i n M e dic al 
Pr o d uct D e v el o p m e nt t o S u p p ort L a b eli n g Cl ai ms. ”  T hr o u g h t his pr oc ess, t h e I A di ary w as d e m o nstr at e d 
t o b e a psyc h o m etric ally v ali d a n d r eli a bl e t o ol t o ass ess I A i n c hil dr e n ( S p o ns or St u dy 8 1 0 P 5 0 1).   
1. 5  St u d y R ati o n al e 
T h e r es ults of t h e P h as e 2 b st u dy i n dic at e d t h at d os es r a n gi n g fr o m  
/ d a y w er e s af e, eff ecti v e 
a n d w ell t ol er at e d.  T his P h as e 3 st u dy s e e ks t o d e m o nstr at e t h e effic acy, s af et y, a n d t ol er a bilit y of S P N-
8 1 0 i n t h e tr e at m e nt of I A i n p ati e nts wit h A D H D i n c o nj u ncti o n wit h st a n d ar d A D H D tr e at m e nt. St u dy 
m e dic ati o n ( S M) will b e giv e n as a divi d e d d os e t wic e d aily ( BI D) wit h or wit h o ut f o o d.  A r a n d o miz e d, 
pl ac e b o-c o ntr oll e d, d o u bl e bli n d, m ultic e nt er, p ar all el gr o u p, fix e d d os e st u dy d esi g n will b e us e d. 
Fr e q u e nc y of I A b e h a vi ors will s erv e as a pr oxy f or I A s e v erit y.  T h e I A di ary will b e us e d t o ass ess t h e 
fr e q u e nc y of I A b e h a vi ors.  T h e I A di ar y w as d e v el o p e d a n d v ali d at e d f or us e as a c o nt e m p or a n e o us, 
e v e nt- driv e n, o bs er v er-r e p ort e d o utc o m e m e as ur e.  It m o nit ors b e h avi ors t h at h a v e b e e n s p ecific ally 
li n k e d t o I A.  It d o es n ot r ely o n l o n g p eri o ds of r ec all or s u bj ecti v e w ei g hti n g of b e h a vi ors.  F or t h es e 
r e as o ns, t h e I A di ar y is u ni q u el y s uit e d t o d et ect c h a n g es i n t h e fr e q u e ncy I A b e h a vi ors, w hic h i n t ur n is 
i n dic ati v e of t h e s e v erit y of I A.    
A d diti o n ally, I A s ev erity a n d i m pr ov e m e nt will b e ass ess e d usi n g Cli nic al Gl o b al I m pr essi o n ( C GI) sc al es 
c o m pl et e d b y b ot h i nv esti g at or a n d c ar e giv er.  S u bj ect a n d c ar e gi v er q u ality of lif e will als o b e 
e v al u at e d.   
T h e eff ect of m oli n d o n e o n b o dy c o m p ositi o n, m et a b olic p ar a m et ers, a n d pr ol acti n will b e e v al u at e d.  
E m er g e nc e of extr a pyr a mi d al s y m pt o ms will b e m o nit or e d. 
2  S T U D Y O BJ E C TI V E S 
2. 1  Pri m ar y O bj ecti v e 
T h e pri m ar y o bj ecti v e is t o ass ess t h e effic acy a n d s af et y of S P N- 8 1 0 i n r e d uci n g t h e fr e q u e ncy of I A 
b e h a vi ors i n p e di atric p ati e nts wit h A D H D w h e n t a k e n i n c o nj u ncti o n wit h st a n d ar d A D H D tr e at m e nt. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
2. 2  S ec o n d ar y O bj ecti v es 
T h e s ec o n d ary o bj ectiv es of t h e st u dy ar e t o ass ess t h e f oll o wi n g:  
 
t h e eff ect of S P N- 8 1 0 o n t h e Cli nic al Gl o b al I m pr essi o n –  I m pr ov e m e nt Sc al e ( C GI-I)  
 
t h e eff ect of S P N- 8 1 0 o n t h e Cli nic al Gl o b al I m pr essi o n –  S ev erity Sc al e ( C GI-S)  
 
t h e eff ect of S P N-8 1 0 o n t h e c hil d’s o v er all h e alt h as m e as ur e d b y t h e C hil d H e alt h 
Q u esti o n n air e P ar e nt F or m 2 8-it e m ( C H Q- P F 2 8) 
 
t h e eff ect of tr e ati n g t h e c hil d wit h S P N- 8 1 0 o n t h e p ar e nt-c hil d r el ati o ns hi p as m e as ur e d b y t h e 
P ar e nti n g Str ess I n d ex –  S h ort F or m v ersi o n 4 ( P SI- 4-S F)   
 
t h e eff ect of S P N- 8 1 0 o n t h e c ar e giv er-c o m pl et e d C GI-I 
 
t h e eff ect of S P N- 8 1 0 o n i n att e nti o n a n d h y p er activit y-i m p ulsivity m e as ur e d b y t h e S N A P-I V 
R ati n g Sc al e 
2. 3  T erti ar y O bj ecti v e 
 
 
 
3  I N V E S TI G A TI O N AL PL A N 
3. 1  R ati o n al e f or St u d y D esi g n, I ncl u di n g C h oic e of Tr e at m e nt Gr o u ps, 
A p pr o pri at e n ess of M e as ur e m e nts 
T h e pr es e nt st u dy is d esi g n e d t o ev al u at e t h e effic acy, s af ety, a n d t ol er a bilit y of S P N- 8 1 0 i n p ati e nts 
a g e d 6 t o 1 2  y e ars wit h A D H D a n d c o m or bi d I A, w h e n t a k e n i n c o nj u ncti o n wit h a st a n d ar d A D H D 
tr e at m e nt.  I n t his p ati e nt p o p ul ati o n, I A b e h a vi ors p ersist, d es pit e m o n ot h er a py tr e at m e nt wit h a n 
F D A- a p pr o v e d A D H D m e dic ati o n, sti m ul a nt or n o n-sti m ul a nt, at a n F D A- a p pr o v e d o pti miz e d d os e. 
A titr ati o n sc h e d ul e will b e f oll o w e d t o e ns ur e a s af e esc al ati o n t o e ac h d os e l ev el.   T h e titr ati o n r at e 
a n d d os e r a n g e u n d er i nv esti g ati o n i n t h e pr es e nt st u dy w er e d e m o nstr at e d t o b e s af e, effic aci o us, a n d 
w ell t ol er at e d i n a si mil ar p ati e nt p o p ul ati o n i n t h e pr e vi o us P h as e 2 b st u dy.  A d mi nistr ati o n of st u dy 
m e dic ati o n will b e r ec or d e d usi n g a n el ectr o nic d osi n g di ar y. 
T h e I A di ar y will s er v e as t h e pri m ary ass ess m e nt t o ol f or effic ac y.  T h e I A di ary is a n e w el ectr o nic 
o bs erv er-r e p ort e d o utc o m e ( e O bs R O) i nstr u m e nt d ev el o p e d by t h e S p o ns or t o r ec or d b e h a vi ors 
ass oci at e d wit h I A.  S ec o n d ar y m e as ur es of effic ac y will i ncl u d e t h e eff ect of S P N- 8 1 0 o n t h e Cli nic al 
Gl o b al I m pr essi o n –  I m pr ov e m e nt Sc al e ( C GI-I), t h e eff ect of S P N- 8 1 0 o n t h e Cli nic al Gl o b al I m pr essi o n –  
S e v erit y Sc al e ( C GI- S), t h e eff ect of S P N- 8 1 0 o n t h e c hil d’s o v er all h e alt h as m e as u r e d by t h e C hil d 
H e alt h Q u esti o n n air e P ar e nt F or m 2 8-it e m ( C H Q- P F 2 8), a n d t h e eff ect of tr e ati n g t h e c hil d wit h S P N- 8 1 0 
o n t h e p ar e nt-c hil d r el ati o ns hi p as m e as ur e d b y t h e P ar e nti n g Str ess I n d ex –  S h ort F or m ( P SI- 4- S F).  T h e 
c hil d’s A D H D s y m pt o ms will b e m e as ur e d usi n g t h e S w a ns o n, N ol a n a n d P el h a m R ati n g Sc al e - R evis e d 
( S N A P-I V). 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S af et y will b e ass ess e d b y t h e m o nit ori n g of A Es, c o nc o mit a nt m e dic ati o ns, vit al si g ns, cli nic al l a b or at or y 
t ests, p hysic al ex a mi n ati o ns, a n d E C Gs, as w ell as b y t h e Si m ps o n-A n g u s Sc al e, t h e B ar n es A k at hisi a 
Sc al e, a n d t h e A b n or m al I nv ol u nt ary M ov e m e nt Sc al e ( AI M S).  T h e sc al es w er e c h os e n t o s p ecific ally 
m o nit or E P S, si nc e y o ut h tr e at e d wit h a nti psyc h otics ar e at gr e at er ris k f or E P S si d e eff ects t h a n a d ults 
( Fi n dli n g 2 0 0 5).  T h es e sc al es w er e utiliz e d i n P h as e 2 st u di es a n d h a v e b e e n us e d i n ot h er cli nic al 
st u di es of aty pic al a nti psyc h otics i n c hil dr e n. 
3. 2  O v er all St u d y D esi g n a n d Pl a n 
Pr ot oc ol 8 1 0 P 3 0 1 is a r a n d o miz e d, pl ac e b o-c o ntr oll e d, d o u bl e bli n d, m ultic e nt er, p ar all el gr o u p, fix e d 
d os e st u dy t o d e m o nstr at e t h e effic acy, s af et y, a n d t ol er a bilit y of S P N- 8 1 0 i n t h e tr e at m e nt of I A i n 
p ati e nts a g e d 6- 1 2  y e ars wit h A D H D i n c o nj u ncti o n wit h st a n d ar d A D H D tr e at m e nt.   T h e st u dy is 
pr es e nt e d sc h e m atic ally i n Fi g ur e 1  a n d Fi g ur e 2 .  T h e st u dy is divi d e d i nt o t hr e e p h as es: Pr e- Tr e at m e nt, 
Tr e at m e nt, a n d C o nv ersi o n/ T a p er. 
F oll o wi n g scr e e ni n g, eli gi bl e s u bj ects will e nt er a fl exi bl e b as eli n e p eri o d, at w hic h ti m e t h e I A di ar y will 
b e iss u e d t o t h e s u bj ect’s pri m ar y c ar e giv er.  At t h e e n d of t h e b as eli n e p eri o d, eli gi bl e s u bj ects  w h os e 
pri m ar y c ar e giv er h as m ai nt ai n e d at l e ast 8 0 % c o m pli a nc e wit h t h e I A di ar y will b e r a n d o miz e d 1: 1: 1 t o 
1 8  m g/ d a y S P N- 8 1 0, 3 6 m g/ d a y S P N- 8 1 0, or pl ac e b o. A d os e titr ati o n sc h e d ul e will b e f oll o w e d, wit h 
d osi n g i n t h e activ e tr e at m e nt gr o u ps i niti at e d at 3 m g/ d a y a n d i ncr e as e d a p pr oxi m at el y ev er y 3 d a ys 
u ntil t h e t ar g et d os e is r e ac h e d.   Aft er c o m pl eti n g t h e t w o- w e e k titr ati o n p eri o d a n d t h e t hr e e - w e e k 
m ai nt e n a nc e p eri o d, s u bj ects will e nt er t h e c o nv ersi o n or t a p eri n g p h as e pri or t o disc o nti n ui n g S M, at 
w hic h ti m e s u bj ects will h av e t h e o pti o n t o e nt er a n o p e n l a b el ext e nsi o n ( OL E) st u dy.  A s u bj ect w h o 
disc o nti n u es d uri n g t h e m ai nt e n a nc e p eri o d pri or t o Visit 6 m ay b e all o w e d t o p artici p at e i n t h e OL E o n 
a c as e- by -c as e b asis o nl y aft er c o ns ult ati o n b et w e e n t h e I nv esti g at or, t h e M e dic al M o nit or a n d t h e 
S p o ns or.  T h e OL E st u dy will b e c o n d uct e d u n d er a s e p ar at e pr ot oc ol.  S u bj ects w h o c h o os e t o 
p artici p at e i n t h e OL E will e nt er t h at st u dy at a d os e of 1 8 m g/ d a y S P N- 8 1 0. 
 
3. 2. 1  
Pr e- Tr e at m e nt P h as e 
3. 2. 1. 1  Scr e e ni n g P eri o d 
Scr e e ni n g will t a k e pl ac e f or u p t o 4 5  d a ys pri or t o r a n d o miz ati o n a n d m ay b e c arri e d o ut ov er m or e 
t h a n o n e visit if n ec ess ary.  Pri or t o c o n d ucti n g a n y scr e e ni n g pr oc e d ur es, writt e n i nf or m e d 
c o ns e nt/ ass e nt m ust b e o bt ai n e d fr o m t h e p ar e nt or l e g al r e pr es e nt ativ e, a n d s u bj ect ( w h e n r e q uir e d). 
E ac h scr e e n e d s u bj ect will b e assi g n e d a s u bj ect n u m b er st arti n g fr o m 1 0 0 1 t o 1 9 9 9 i n a s e q u e nti al 
m a n n er. St aff at st u dy sit es ar e e nc o ur a g e d t o c o m pl et e scr e e ni n g pr oc e d ur es as e arl y as p ossi bl e t o 
pr o vi d e m or e fl exi bility i n t h e b as eli n e p eri o d f or t h e c ar e gi v ers t o ac hi ev e I A di ary c o m pli a nc e (s e e 
S ecti o n 3. 2. 1. 2 ). 
T h e R- M O A S a n d C GI - S will b e a d mi nist er e d t o d et er mi n e e ntry t o t h e b as eli n e p eri o d of t h e st u dy a n d 
als o t o d et er mi n e eli gi bilit y f or r a n d o miz ati o n t o tr e at m e nt.  T h e Viti ell o A g gr essi o n Sc al e will b e us e d t o 
e v al u at e s u bty p e of a g gr essi o n ( pl a n n e d vs. i m p ulsiv e); o nl y t h os e c hil dr e n w h o sc or e as pr e d o mi n a ntl y 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
i m p ulsiv e will b e i ncl u d e d. T h e di a g n osis of A D H D will b e c o nfir m e d wit h t h e Sc h e d ul e f or Aff ectiv e 
Dis or d ers a n d Sc hiz o p hr e ni a f or Sc h o ol- a g e d C hil dr e n — Pr es e nt  a n d Lif eti m e V ersi o ns 2 0 1 3 ( K- S A D S- PL 
2 0 1 3). T h e K- S A D S- PL 2 0 1 3 is a s e mi-str uct ur e d di a g n ostic i nt ervi e w d esi g n e d t o di a g n os e c urr e nt a n d 
p ast e pis o d es of psyc h o p at h ol o gy i n c hil dr e n a n d a d ol esc e nts acc or di n g t o D S M- 5 crit eri a.   T h e 
I ntr o d uct or y a n d Scr e e n I nt er vi e ws will b e c o m pl et e d.  T h e Scr e e n I nt er vi e w will ass ess t h e diff er e nt 
di a g n os es a n d d et er mi n e w hic h s u p pl e m e nts s h o ul d b e c o m pl et e d.  S u p pl e m e nt 4 ( N e ur o d e v el o p m e nt, 
Disr u pti v e a n d C o n d uct Dis or d ers) m ust b e c o m pl et e d t o ass ess A D H D, O D D, C D , Tic a n d A S D ( A utis m 
S p ectr u m Dis or d er).  If a n excl usi o n ary di a g n osis is c o nfir m e d, t h e r e m ai n d er of t h e di a g n ostic will n ot 
b e c o m pl et e d a n d t h e s u bj ect will b e d e e m e d a scr e e n f ail ur e.   
3. 2. 1. 2  B as eli n e P eri o d 
S u bj ects w h o m e et st u dy e ntr y r e q uir e m e nts will pr oc e e d t o t h e fl exi bl e b as eli n e p eri o d.  At Visit 2 a n I A 
di ary d evic e (L o g P a d) will b e iss u e d t o t h e pri m ar y c ar e giv er.  T h e pri m ary a n d (if assi g n e d) s ec o n d ary 
c ar e giv ers will r ec ei v e tr ai ni n g o n t h e us e of t h e I A di ar y. Ev er y eff ort will b e m a d e t o pr ovi d e a d e q u at e 
c ar e giv er tr ai ni n g o n t h e us e of t h e I A di ar y at Visit 2 a n d ac k n o wl e d g e m e nt of tr ai ni n g will b e c a pt ur e d 
o n t h e d e vic e.  
F oll o wi n g at l e ast 1 5 d a ys of I A di ary us e, c ar e giv er c o m pli a nc e wit h t h e I A di ary will b e ass ess e d.  
C o m pli a nc e will b e c alc ul at e d as t h e p erc e nt a g e of d ays o v er t h e p ast 1 5 d a ys d uri n g t h e b as eli n e p eri o d 
f or w hic h a n ev e ni n g di ar y w as c o m pl et e d. S u bj ects w h os e c ar e giv ers d e m o nstr at e at l e ast 8 0 % 
c o m pli a nc e will b e eli gi bl e f or r a n d o miz ati o n a n d c o nti n u e i nt o t h e titr ati o n p eri o d. 
S u bj ects w h os e c ar e giv ers d o n ot r e ac h 8 0 % c o m pli a nc e d uri n g t h e first 1 5 d ays of t h e b as eli n e p eri o d 
m a y b e all o w e d t o c o nti n u e t o us e t h e di ary f or u p t o 1 5 a d diti o n al d ays.  F or t h es e s u bj ects, c ar e giv ers 
will r ec ei v e r e m e di al tr ai ni n g o n t h e us e of t h e I A di ary.  D uri n g t his ti m e, c ar e giv er c o m pli a nc e wit h t h e 
I A di ar y will b e m o nit or e d d aily b y st u dy sit e p ers o n n el o v er t h e p ast 1 5-d a ys as a “r olli n g wi n d o w”.  
W h e n t h e c ar e giv ers’ p erf or m a nc e wit h t h e I A di ary i m pr ov es s uc h t h at t h e c ar e gi v ers ar e a bl e t o 
d e m o nstr at e at l e ast 8 0 % c o m pli a nc e o v er t h e p ast 1 5- d a y r olli n g wi n d o w, t h e s u bj ect will b e eli gi bl e 
f or r a n d o miz ati o n a n d all o w e d t o c o nti n u e i nt o t h e titr ati o n p eri o d.  
Alt h o u g h t h er e ar e u p t o 3 0 d a ys a v ail a bl e f or e ac h of t h e scr e e ni n g a n d t h e b as eli n e p eri o d, t h e t ot al 
d ur ati o n of scr e e ni n g a n d b as eli n e p eri o ds m a y n ot e xc e e d 4 5 d a ys.  
R escr e e ni n g 
As a g e n er al r ul e, r escr e e ni n g of s u bj ects is n ot all o w e d.  T h e o nl y exc e pti o n t o t his will b e f or s u bj ects 
w h o f ail e d scr e e ni n g d u e t o c ar e giv er n o n-c o m pli a nc e wit h t h e I A di ary u n d er pr ot oc ol v ersi o n 5. 0. 
T h es e s u bj ects m ay b e r escr e e n e d t o p artici p at e i n t h e st u dy u n d er c urr e nt pr ot oc ol. T h es e s u bj ects will 
b e assi g n e d a n e w s u bj ect I D n u m b er a n d will c o m pl et e all st u dy scr e e ni n g pr oc e d ur es.   

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 3 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
3. 2. 2  
Tr e at m e nt P h as e   
3. 2. 2. 1  R a n d o miz ati o n 
I ncl usi o n/ excl usi o n crit eri a will b e r e- ass ess e d t o v erify eli gi bilit y pri or t o st u dy r a n d o miz ati o n at t h e e n d 
of Visit 3 ( R a n d o miz ati o n).  Eli gi bl e s u bj ects w h os e pri m ar y c ar e giv er h as m ai nt ai n e d at l e ast 8 0 % 
c o m pli a nc e wit h t h e I A di ary will b e r a n d o miz e d.  Eli gi bl e s u bj ects w h o c o m pl et e t h e b as eli n e p eri o d 
a n d m e et t h e r e q uir e m e nts f or t h e d o u bl e bli n d st u dy will  b e r a n d o miz e d at Visit 3 ( D a y 1) i n a 1: 1: 1 
r ati o t o r ec ei v e 1 8 m g/ d ay, 3 6 m g/ d a y S P N- 8 1 0, or pl ac e b o a n d pr oc e e d t o t h e titr ati o n p eri o d, w hic h 
will b e t w o w e e ks.  
3. 2. 2. 2  Titr ati o n P eri o d 
S u bj ects will b e titr at e d t o m ai nt e n a nc e d os e ov er a p eri o d of 2 w e e ks. 
3. 2. 2. 3  M ai nt e n a nc e P eri o d 
F oll o wi n g d os e titr ati o n, s u bj ects o n acti v e tr e at m e nt will b e m ai nt ai n e d at t h eir d esi g n at e d d os e l e v el 
f or 3 w e e ks.   
3. 2. 3  
C o n v ersi o n/ T a p er P h as e 
All s u bj ects w h o c o m pl et e t h e r a n d o miz e d, d o u bl e bli n d p orti o n of st u dy 8 1 0 P 3 0 1 will h av e t h e o pti o n 
t o p artici p at e i n a n OL E st u dy (st u dy pr ot oc ol 8 1 0 P 3 0 4) i n w hic h all s u bj ects will r ec eiv e acti v e S M 
tr e at m e nt.  S u bj ects c h o osi n g t o p artici p at e will r ec eiv e bli n d e d c o nv ersi o n m e dic ati o n kits, a n d t h eir 
t ot al d ail y d os e f or t h e o p e n l a b el ext e nsi o n will b e c o nv ert e d t o 1 8 m g / d ay (Fi g ur e 1 ).  T h os e s u bj ects 
w h o d o n ot el ect t o p artici p at e i n t his ext e nsi o n will b e t a p er e d off S M ( Fi g ur e 2 ).   
3. 2. 4  
E n d of St u d y / E arl y T er mi n ati o n 
S u bj ects will r et ur n t o t h e st u dy sit e f or a fi n al visit, aft er c o m pl eti n g t h e 1- w e ek T a p er/ C o nv ersi o n 
P eri o d.  T h os e s u bj ects w h o el ect t o c o nti n u e i n t h e OL E st u dy will h av e pr oc e d ur es p erf or m e d f or t h at 
st u dy as w ell.   S u bj ects w h o disc o nti n u e fr o m t h e st u dy d uri n g t h e m ai nt e n a nc e p eri o d will b e off er e d a 
T a p er kit a n d will r et ur n t o t h e st u dy sit e f or a f oll o w- u p visit ( E O S).  S u bj ects w h o disc o nti n u e d uri n g 
t h e titr ati o n p eri o d will n ot r ec eiv e a t a p er kit a n d will o nl y c o m pl et e t h e E O S pr oc e d ur es. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4  S T U D Y M E T H O D S 
4. 1  S el ecti o n of St u d y P o p ul ati o n 
T h e t ar g et p o p ul ati o n will b e m al e a n d f e m al e s u bj ects a g e d 6 t o 1 2 y e ars wit h I A a n d A D H D.  S M will b e 
a d mi nist er e d i n c o nj u ncti o n wit h t h e s u bj ect’s st a n d ar d A D H D tr e at m e nt.  A p pr oxi m at el y 3 3 0 s u bj ects 
will b e r a n d o miz e d i n t his cli nic al i n v esti g ati o n.   
4. 1. 1  
I ncl usi o n Crit eri a 
1.  H e alt h y m al e or f e m al e s u bj ects, a g e 6 t o 1 2  y e ars at t h e ti m e of scr e e ni n g.  
2.  Di a g n osis of A D H D acc or di n g t o t h e Di a g n ostic a n d St atistic al M a n u al of M e nt al Dis or d ers- 5   
( D S M- 5 c o nfir m e d by  t h e Sc h e d ul e f or Aff ecti v e Dis or d ers a n d Sc hiz o p hr e ni a f or Sc h o ol- a g e d 
C hil dr e n –  Pr es e nt a n d Lif eti m e V ersi o n 2 0 1 3 ( K- S A D S-PL  2 0 1 3).  
3.  R etr os p ectiv e M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S) sc or e of 2 4 at scr e e ni n g. 
4.  C GI - S sc or e of at l e ast m o d er at ely ill at b ot h Scr e e ni n g a n d R a n d o miz ati o n.  
5.  Viti ell o A g gr essi o n Sc al e sc or e fr o m - 2 t o - 5 at Scr e e ni n g. 
6.  Fr e e of a nti psyc h otic m e dic ati o n f or at l e ast t w o w e eks pri or t o Visit 2.  
7.  M o n ot h er a py tr e at m e nt wit h F D A- a p pr ov e d o pti miz e d A D H D m e dic ati o n ( ps yc h osti m ul a nt or 
n o n-sti m ul a nt) at a n F D A- a p pr o v e d d os e f or at l e ast o n e m o nt h pri or t o Scr e e ni n g, a n d willi n g 
t o m ai nt ai n t h at d os e t hr o u g h o ut t h e B as eli n e a n d Tr e at m e nt p eri o d.   
8.  α 2 - a dr e n er gic a g o nists ( e. g. cl o ni di n e a n d g u a nf aci n e) us e d f or a n y ot h er r e as o n exc e pt f or 
m o n ot h er a py tr e at m e nt f or A D H D ( e. g. a g gr essi o n or i ns o m ni a) m ust b e disc o nti n u e d at l e ast 
t w o- w e e ks pri or t o Visit 2. 
9.  M e dic ally h e alt hy a n d wit h cli nic all y n or m al l a b or at ory pr ofil es, vit al si g ns, a n d 
el ectr oc ar di o gr a ms ( E C Gs). 
1 0.  W ei g ht of at l e ast 2 0 k g. 
1 1.  A bl e a n d willi n g t o s w all o w t a bl ets w h ol e a n d n ot c h e w e d, c ut or cr us h e d.  
1 2.  Writt e n I nf or m e d C o n s e nt o bt ai n e d fr o m t h e s u bj ect’s p ar e nt or l e g al r e pr es e nt ati v e, a n d 
writt e n I nf or m e d Ass e nt o bt ai n e d fr o m t h e s u bj ect if a p pr o pri at e. 
1 3.  M e as ur e m e nt of c o m pli a nc e ≥ 8 0 % f or c o m pl eti o n of I A Di ary d uri n g B as eli n e P eri o d.  
4. 1. 2  
E xcl usi o n Crit eri a 
1.  B o dy M ass I n d ex ( B MI) i n 9 9 t h p erc e ntil e or a b o v e. 
2.  C urr e nt or lif eti m e di a g n osis of e pil e ps y, m aj or d e pr essi v e dis or d er, bi p ol ar dis or d er, 
sc hiz o p hr e ni a or r el at e d dis or d er, p ers o n alit y dis or d er, T o ur ett e’s dis or d er, or psyc h osis n ot 
ot h er wis e s p ecifi e d. 
3.  C urr e ntl y m e eti n g D S M- 5 crit eri a f or a utis m s p ectr u m dis or d er, p er v asiv e d e v el o p m e nt al 
dis or d er, o bs essi v e c o m p ulsi v e dis or d er, p ost-tr a u m atic str ess dis or d er, or a ny ot h er a nxi ety 
dis or d er as pri m ary di a g n osis. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4.  Us e of a ntic o nv uls a nts i ncl u di n g c ar b a m az e pi n e a n d v al pr oic aci d, a nti d e pr ess a nts, m o o d 
st a biliz ers i ncl u di n g lit hi u m, b e nz o di az e pi n es, c h oli n est er as e i n hi bit ors or a ny dr u g k n o w n t o 
i n hi bit C Y P 2 D 6 acti vity wit hi n t w o w e e ks of Visit 2.  
5.  Us e of h er b al s u p pl e m e nts wit hi n o n e w e e k of Visit 2. 
6.  K n o w n or s us p ect e d i nt elli g e nc e q u oti e nt (I Q) < 7 0. 
7.  U nst a bl e e n d ocri n ol o gic al or n e ur ol o gic al c o n diti o ns w hic h c o nf o u n d t h e di a g n osis or ar e a 
c o ntr ai n dic ati o n t o tr e at m e nt wit h a nti ps yc h otics. 
8.  S uici d alit y, d efi n e d as eit h er acti v e s uici d al pl a n/i nt e nt or acti v e s uici d al t h o u g hts i n t h e six 
m o nt hs b ef or e t h e Scr e e ni n g Visit or m or e t h a n o n e lif eti m e s uici d e att e m pt.   
9.  Pr e g n a nc y or r ef us al t o pr actic e c o ntr ac e pti o n d uri n g t h e st u dy (f or f e m al e s u bj ects of 
c hil d b e ari n g p ot e nti al a n d s ex u ally activ e m al es). 
1 0.  S u bst a nc e or alc o h ol us e d uri n g t h e l ast t hr e e m o nt hs. 
1 1.  Uri n e dr u g t est at scr e e ni n g t h at is p ositiv e f or alc o h ol or dr u gs of a b us e. 
1 2.  K n o w n all er g y or s e nsitivity t o m oli n d o n e h y dr oc hl ori d e.  
1 3.  A ny r e as o n w hic h, i n t h e o pi ni o n of t h e I n v esti g at or or t h e S p o ns or, w o ul d pr e v e nt t h e s u bj ect 
a n d s u bj ect’s c ar e giv er fr o m p artici p ati n g i n t h e st u dy or c o m plyi n g wit h t h e st u dy pr oc e d ur es.  
1 4.  Us e of a n i nv esti g ati o n al dr u g or p artici p ati o n i n a n i n v esti g ati o n al st u dy wit hi n 3 0 d a ys pri or t o 
Visit 2. 
4. 2  Sc h e d ul e of Visits a n d Pr oc e d ur es 
All s u bj ects w h o ar e r a n d o miz e d a n d t ak e a ny S M will b e f oll o w e d acc or di n g t o t h e pr ot oc ol r e g ar dl ess 
of t h e n u m b er of d os es of S M t a k e n, u nl ess c o ns e nt f or f oll o w- u p is wit h dr a w n.  T h e S p o ns or, or t h e 
S p o ns or’s d esi g n e e, m ust b e n otifi e d of all d evi ati o ns fr o m t h e pr ot oc ol visits or pr oc e d ur es, a n d t h es e 
pr oc e d ur es, if a p plic a bl e, will b e r esc h e d ul e d or p erf or m e d at t h e n e ar est p ossi bl e ti m e t o t h e ori gi n al 
sc h e d ul e.  S u bj ects will b e i nstr uct e d t o c all st u dy p ers o n n el t o r e p ort a n y a b n or m aliti es d uri n g t h e 
i nt er v als i n b et w e e n st u dy visits a n d t o c o m e t o t h e st u dy sit e if m e dic al e v al u ati o n is n e e d e d a n d as t h e 
ur g e nc y of t h e sit u ati o n i n dic at es.  U nsc h e d ul e d visits m ay b e c o n d uct e d at t h e discr eti o n of t h e 
i nv esti g at or t hr o u g h o ut all st u dy p eri o ds.  T h e m e dic al m o nit or m ust b e c o nt act e d pr o m ptl y i n t h e 
e v e nt t h at a n y cli nic ally si g nific a nt fi n di n gs or i nf or m ati o n ar e o bt ai n e d d uri n g t h e u nsc h e d ul e d visit. 
T his s h o ul d b e c a pt ur e d i n t h e a p pr o pri at e e C R F.  F or e m er g e nc y a n d ot h er u nsc h e d ul e d visits t o a 
m e dic al f acility ot h er t h a n t h e st u dy sit e, m e dic al r ec or ds will b e o bt ai n e d by t h e I nv esti g at or or 
q u alifi e d d esi g n e e as s o urc e d at a f or st u dy f oll o w- u p . 
T a bl e 1  pr es e nts t h e sc h e d ul e of visits a n d pr oc e d ur es f or t h e st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n 
writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T a bl e 1:  Sc h e d ul e of Visits a n d Pr oc e d ur es 
P h as e  
Pr e -tr e at m e nt 
Tr e at m e nt  
C o n v ersi o n/  
T a p er  
P eri o d  
Scr e e ni n g  
B as eli n e  
Titr ati o n  
M ai nt e n a nc e  
VI SI T N U M B E R  
1  
2  
3  
4  
5  
6  
7  
D A Y  
-4 5  
-1 5  
1  
8  
1 5  
3 6  
4 3  
WI N D O W ( D A Y S)  
4 5 d pri or t o 
V isit 3  
≥1 5 d pri or t o  
V isit 3  
0 c 
7 d ± 2 d fr o m 
Visit 3  
1 4 d ± 2 d fr o m 
Visit 3  
2 1 d ± 3 d fr o m 
Visit 5  
7 d ± 1 d fr o m 
Visit 6  
I nf or m e d C o ns e nt/ Ass e nt a 
X  b 
 
 
 
 
 
 
R -M O A S, K -S A D S -PL 2 0 1 3 & Viti ell o 
A g gr essi o n Sc al e  
X  
 
 
 
 
 
 
M e dic al Hist or y  
X  
 
X d 
 
 
 
 
D e m o gr a p hics  
X  
 
 
 
 
 
 
P h ysic al Ex a mi n ati o n  
X  
 
 
 
 
X  
 
E C G ( 1 2 -l e a d) 
X  
 
 
X  
 
X  
 
I ncl usi o n/ Excl usi o n Crit eri a 
X  
 
 
 
 
 
 
R a n d o miz ati o n  
 
 
X b ,e 
 
 
 
 
Uri n e Dr u g Scr e e n  
X  
 
X  
 
 
 
 
Uri n e Pr e g n a nc y T est f 
X  
 
X  
 
 
 
X  
Di ar y Tr ai ni n g & Distri b uti o n or E v al u ati o n  
 
X  
X  e 
X  
X  
X  
 
Vit al Si g ns g 
X  
 
 
 
 
 
X  
W ei g ht, h ei g ht , B MI 
X  
 
X  
X  
X  
X  
X  
H e m at ol o gy/c h e mistry/ Uri n al ysis  
X  
 
X  
 
 
X  
X  
P K Bl o o d  S a m pli n g  
 
 
 
X h 
X h 
 
 
C ol u m bi a S uici d e S ev erit y R ati n g Sc al e 
( C S S R S) 
X  
 
X  
X  
X  
X  
X  
I nv esti g at or C GI -S  
X  
 
X  
X  
X  
X  
 
C ar e giv er a n d i nv esti g at or C GI -I 
 
 
 
X  
X  
X  
 
Effic ac y sc al es ( S N A P -I V, C H Q-P F 2 8, P SI -4 -S F ) 
 
 
X  
 
 
X  
 
S af ety Sc al es ( Si m ps o n -A n g us, B ar n es, AI M S)  
 
 
X  
X  
X  
X  
X  
I nfr e q u e nt B e h a vi ors C h ec klist 
 
 
X  
X  
X  
X  
 
A dv ers e E v e nts  
 
 
X  
X  
X  
X  
X  
C o nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
X  
X  
Dr u g Dis p e ns ati o n  
 
 
X b 
 
X  
X  
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n 
writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
P h as e  
Pr e -tr e at m e nt 
Tr e at m e nt  
C o n v ersi o n/  
T a p er  
P eri o d  
Scr e e ni n g  
B as eli n e  
Titr ati o n  
M ai nt e n a nc e  
VI SI T N U M B E R  
1  
2  
3  
4  
5  
6  
7  
D A Y  
-4 5  
-1 5  
1  
8  
1 5  
3 6  
4 3  
WI N D O W ( D A Y S)  
4 5 d pri or t o 
V isit 3  
≥1 5 d pri or t o  
V isit 3  
0 c 
7 d ± 2 d fr o m 
Visit 3  
1 4 d ± 2 d fr o m 
Visit 3  
2 1 d ± 3 d fr o m 
Visit 5  
7 d ± 1 d fr o m 
Visit 6  
Dr u g R et ur n a n d C o m pli a nc e  
 
 
 
 
X  
X  
X  
Di ar y R et ur n  
 
 
 
 
 
 
X  
a  
Writt e n c o ns e nt m ust b e o bt ai n e d pri or t o p erf or mi n g a n y st u dy -r el at e d pr oc e d ur e. 
b  
Acc ess I W R S . 
c 
Visit 3 will occ ur at l e ast 1 5 d ays f oll o wi n g Visit 2  
d  
Ass ess f or a n y cli nic ally si g nific a nt c h a n g e i n M e dic al Hist ory si nc e scr e e ni n g . 
e  
Di ary c o m pli a nc e m ust b e at l e ast 8 0 % ( mi ni m u m of 1 2 d ays o ut of 1 5 ) t o q u alify f or 
r a n d o miz ati o n. 
 
f 
T o b e p erf or m e d f or f e m al e s u bj ects of c hil d b e ari n g p ot e nti al  pri or t o a d mi nistr ati o n of 
first d os e of S M a n d will h av e t o b e t est e d as n e g ativ e f or t h e s u bj ect t o c o nti n u e i n 
t h e st u dy. 
g  
H e art R at e ( H R), bl o o d pr ess ur e ( B P), t e m p er at ur e, a n d r es pir at or y r at e will b e 
m e as ur e d.  
h  
T ot al of 5 P K bl o o d s a m pl es will b e o bt ai n e d ov er o n e or t w o visits ( Visit 4 a n d/ or Visit 5)  
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4. 2. 1  
Visit 1 
Pri or t o c o n d ucti n g a n y scr e e ni n g pr oc e d ur es, writt e n I nf or m e d C o ns e nt m ust b e o bt ai n e d fr o m t h e 
p ar e nt or l e g al r e pr es e nt ati v e, a n d, if a p pr o pri at e, I nf or m e d Ass e nt fr o m t h e s u bj ect.  S u bj ect scr e e ni n g 
pr oc e d ur es will b e p erf or m e d wit hi n 4 5  d ays pri or t o Visit 3 a n d m ay b e d o n e o n m or e t h a n o n e d a y.  
A b n or m al r es ults o n scr e e ni n g l a b or at or y t ests m a y b e r e p e at e d at t h e discr eti o n of t h e I nv esti g at or .  
T h e f oll o wi n g pr oc e d ur es will b e p erf or m e d at Visit 1: 
1.  O bt ai n writt e n i nf or m e d c o ns e nt a n d ass e nt. 
2.  O bt ai n d e m o gr a p hic i nf or m ati o n, m e dic al hist ory 
3.  Acc ess I nt er activ e W e b R es p o ns e Syst e m (I W R S) f or s u bj ect n u m b er 
4.  A d mi nist er K- S A D S- PL  2 0 1 3 f or c o nfir m ati o n of A D H D di a g n osis 
5.  A d mi nist er Viti ell o A g gr essi o n Sc al e 
6.  A d mi nist er R- M O A S 
7.  A d mi nist er I nv esti g at or C GI- S 
8.  P erf or m p hysic al ex a mi n ati o n 
9.  R ec or d vit al si g ns ( H R, B P, t e m p er at ur e, a n d R R), h ei g ht, w ei g ht a n d B MI 
1 0.  P erf or m 1 2-l e a d E C G 
1 1.  C oll ect bl o o d s a m pl es f or h e m at ol o gy a n d c h e mistry 
1 2.  A d mi nist er C- S S R S 
1 3.  C oll ect uri n e s a m pl e f or uri n al ysis a n d uri n e dr u g scr e e n ( all s u bj ects), a n d pr e g n a nc y t est 
( F O C B P o nly) 
1 4.  Ass ess a n d r ec or d c o nc o mit a nt m e dic ati o ns 
1 5.  Ass ess i ncl usi o n/ excl usi o n crit eri a 
 
4. 2. 2  
Visit 2 
Visit 2 will occ ur at l e ast 1 5 d a ys pri or t o Visit 3.  Pl e as e n ot e t h at, p er pr ot oc ol a n d wit hi n t h e E D C, Visit 
1 a n d Visit 2 m ay occ ur o n t h e s a m e d ay. 
1.  Pr ovi d e tr ai ni n g f or I A di ary a n d d osi n g di ary m o d ul e 
2.  Distri b ut e d e vic e  
3.  Ass ess a n d r ec or d c o nc o mit a nt m e dic ati o ns 
4. 2. 3  
Visit 3 
Visit 3 will occ ur at l e ast 1 5 d a ys f oll o wi n g Visit 2 acc or di n g t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es. 
1.  A d mi nist er effic acy sc al es (S N A P-I V, C H Q- P F 2 8, P SI- 4- S F)  
2.  Ass ess I A di ary c o m pli a nc e / r evi e w tr ai ni n g as n ec ess ar y 
3.  C o nfir m eli gi bilit y t o r a n d o miz e t o st u dy m e dic ati o n tr e at m e nt 
4.  R a n d o miz e s u bj ect vi a I W RS 
5.  A d mi nist er I nv esti g at or C GI- S 
6.  A d mi nist er I nfr e q u e nt B e h a vi ors C h ecklist 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
7.  A d mi nist er s af ety sc al es ( Si m ps o n- A n g us, B ar n es A k at hisi a, AI M S) 
8.  R ec or d h ei g ht, w ei g ht, a n d B MI 
9.  C oll ect bl o o d s a m pl es f or h e m at ol o gy/c h e mistry 
1 0.  C oll ect uri n e s a m pl es f or uri n al ysis, uri n e dr u g scr e e n ( all s u bj ects), a n d pr e g n a ncy t est ( F O C B P 
o nl y)  
1 1.  A d mi nist er C- S S R S 
1 2.  R ec or d c o nc o mit a nt m e dic ati o n 
1 3.  Ass ess f or a ny cli nic ally si g nific a nt c h a n g e i n M e dic al Hist or y 
1 4.  Dis p e ns e S M vi a I W R S.   
1 5.  R e vi e w tr ai ni n g o n d osi n g di ary m o d ul e 
1 6.  Ass ess a dv ers e ev e nts ( p ost- d os e) 
4. 2. 4  
Visit 4 
Visit 4 will occ ur 7 ( ± 2) d a ys f oll o wi n g Visit 3 acc or di n g t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es. 
1.  A d mi nist er I nv esti g at or C GI- S 
2.  A d mi nist er c ar e giv er a n d i nv esti g at or-c o m pl et e d C GI-I 
3.  A d mi nist er I nfr e q u e nt B e h a vi ors C h ecklist 
4.  A d mi nist er s af ety sc al es ( Si m ps o n- A n g us, B ar n es A k at hisi a, AI M S) 
5.  R ec or d h ei g ht, w ei g ht, a n d B MI 
6.  P erf or m 1 2-l e a d E C G 
7.  C oll ect bl o o d s a m pl es f or P K a n al ysis 
8.  A d mi nist er C- S S R S 
9.  R ec or d c o nc o mit a nt m e dic ati o n 
1 0.  R e vi e w I A di ary c o m pli a nc e a n d pr o vi d e tr ai ni n g as r e q uir e d 
1 1.  C oll ect A Es 
1 2.  R e vi e w d osi n g di ar y c o m pli a nc e a n d pr ovi d e tr ai ni n g as r e q uir e d 
4. 2. 5  
Visit 5 
Visit 5 will occ ur 1 4 ( ± 2) d ays f oll o wi n g Visit 3 acc or di n g t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es. 
1.  A d mi nist er I nv esti g at or C GI- S 
2.  A d mi nist er c ar e giv er a n d i nv esti g at or-c o m pl et e d C GI-I 
3.  A d mi nist er I nfr e q u e nt B e h a vi ors C h ecklist 
4.  A d mi nist er s af ety sc al es ( Si m ps o n- A n g us, B ar n es A k at hisi a, AI M S) 
5.  R ec or d h ei g ht, w ei g ht, a n d B MI 
6.  C oll ect bl o o d s a m pl es f or P K a n al ysis 
7.  A d mi nist er C- S S R S 
8.  R ec or d c o nc o mit a nt m e dic ati o n 
9.  R e vi e w I A di ary c o m pli a nc e a n d pr o vi d e tr ai ni n g as r e q uir e d 
1 0.  C oll ect A Es 
1 1.  C oll ect r et ur n e d S M; ass ess tr e at m e nt c o m pli a nc e 
1 2.  R e vi e w d osi n g di ar y c o m pli a nc e a n d pr ovi d e tr ai ni n g as r e q uir e d  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 3.  Dis p e ns e S M 
4. 2. 6  
Visit 6 
Visit 6 will occ ur 2 1 ( ± 3) d ays f oll o wi n g Visit 5 acc or di n g t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es.   
1.  A d mi nist er effic acy sc al es (I nv esti g at or C GI- S, c ar e giv er a n d i n v esti g at or C GI-I, S N A P-I V, C H Q-
P F 2 8, P SI- 4- S F)  
2.  A d mi nist er I nfr e q u e nt B e h a vi ors C h ecklist 
3.  A d mi nist er s af ety sc al es ( Si m ps o n- A n g us, B ar n es A k at hisi a, AI M S) 
4.  R ec or d h ei g ht, w ei g ht, a n d B MI 
5.  P erf or m 1 2 -l e a d E C G 
6.  P erf or m p hysic al ex a mi n ati o n 
7.  C oll ect bl o o d s a m pl es f or h e m at ol o gy/c h e mistry 
8.  C oll ect uri n e s a m pl e f or uri n al ysis 
9.  A d mi nist er C- S S R S 
1 0.  R ec or d c o nc o mit a nt m e dic ati o n 
1 1.  R e vi e w I A di ary c o m pli a nc e a n d pr o vi d e tr ai ni n g as r e q uir e d 
1 2.  C oll ect A Es 
1 3.  C oll ect r et ur n e d S M; ass ess tr e at m e nt c o m pli a nc e 
1 4.  R e vi e w d osi n g di ar y c o m pli a nc e a n d pr ovi d e tr ai ni n g as r e q uir e d  
1 5.  D et er mi n e w h et h er s u bj ect wis h es t o p artici p at e i n o p e n-l a b el ext e nsi o n  
1 6.  Dis p e ns e S M ( eit h er C o nv ersi o n or T a p er b as e d u p o n s u bj ect’s d ecisi o n a b o ut p art ici p ati o n i n 
o p e n-l a b el ext e nsi o n) 
4. 2. 7  
Visit 7 
Visit 7 will occ ur 7 ( ± 1) d a ys f oll o wi n g Visit 6 acc or di n g t o t h e Sc h e d ul e of Visits a n d Pr oc e d ur es.  T h es e 
pr oc e d ur es will als o b e p erf or m e d f or p ati e nts w h o disc o nti n u e e arl y.  P ati e nts w h o disc o nti n u e e arl y 
aft er Visit 5 will b e off er e d a t a p er kit. 
1.  A d mi nist er s af ety sc al es ( Si m ps o n- A n g us, B ar n es A k at hisi a, AI M S) 
2.  R ec or d vit al si g ns ( H R, B P, t e m p er at ur e, a n d R R), h ei g ht, w ei g ht a n d B MI 
3.  C oll ect uri n e s a m pl e f or pr e g n a nc y t est ( F O C B P o nl y) 
4.  A d mi nist er C- S S R S 
5.  R ec or d c o nc o mit a nt m e dic ati o n 
6.  C oll ect A Es 
7.  C oll ect S M a n d ass ess tr e at m e nt c o m pli a nc e 
8.  C oll ect d evic e 
9.  C o m pl et e/ disc o nti n u e s u bj ect 
1 0.  C oll ect bl o o d s a m pl es f or h e m at ol o gy/c h e mistry 
1 1.  C oll ect uri n e s a m pl e f or uri n al ysis 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
4. 2. 8  
P h ar m ac o ki n etic S a m pl e C oll ecti o n 
All bl o o d s a m pl es f or P K a n al ysis will b e dr a w n at t h e cli nic al sit e.  A t ot al of 5 bl o o d s a m pl es ( 4 mL e ac h) 
will b e t a k e n f or P K a n alysis o v er t h e c o urs e of t h e st u dy.  T h es e will i ncl u d e pr e- a n d p ost- d os e s a m pl es 
o bt ai n e d o v er o n e visit ( Visit 4 or Visit 5) or o v er t w o visits ( Visit 4 a n d Visit 5).   
If t h e s u bj ect d eci d es t o c o m pl et e t h e P K s a m pli n g ov er o n e visit t h e n h e/s h e will arriv e at t h e cli nic i n 
t h e m or ni n g pri or t o t aki n g t h e m or ni n g d os e.  A P K s a m pl e will b e dr a w n pr e- d os e; t h e n t h e d os e will 
b e o bs er v e d i n t h e cli nic.  P ost- d os e P K s a m pl es will b e t a k e n at a p pr oxi m at el y 1 h o ur, 2 h o urs, 4 h o urs 
a n d 6 h o urs aft er t h e ti m e of t h e o bs er v e d d os e.  P K s a m pl es s h o ul d b e o bt ai n e d wit hi n 1 5 mi n ut es of 
t h e 1 h o ur a n d 2 h o ur ti m e p oi nts a n d wit hi n 3 0 mi n ut es of t h e 4 h o ur a n d 6 h o ur ti m e p oi nts.  
If t h e s u bj ect d eci d es t o c o m e f or t h e P K s a m pli n g o v er t w o visits, t h e n o n o n e visit t h e s u bj ect will 
arri v e at t h e cli nic i n t h e m or ni n g, pri or t o t a ki n g t h eir m or ni n g d os e. A P K s a m pl e will b e dr a w n pr e-
d os e; t h e n t h e d os e will b e o bs erv e d i n t h e cli nic.  P ost- d os e P K s a m pl es will b e t a k e n at a p pr oxi m at el y 
1 h o ur a n d 2 h o urs aft er t h e ti m e of t h e o bs erv e d d os e. P K s a m pl es s h o ul d b e o bt ai n e d wit hi n 1 5 
mi n ut es of t h e t ar g et e d ti m e p oi nts.  At t h e ot h er visit, s u bj ects will arri v e at t h e cli nic aft er t aki n g t h eir 
m or ni n g d os e.  P K s a m pl es will b e t a k e n at a p pr oxi m at el y 4 h o urs a n d 6 h o urs aft er t h e ti m e t h at t h e 
m or ni n g d os e w as t a k e n.  P K s a m pl es s h o ul d b e o bt ai n e d wit hi n 3 0 mi n ut es of t h e t ar g et e d ti m e p oi nts. 
Bl o o d s a m pl es will b e c oll ect e d a n d pr oc ess e d as p er i nstr ucti o ns i n t h e L a b or at or y M a n u al. 
4. 3  Tr e at m e nts 
4. 3. 1  
Tr e at m e nts A d mi nist er e d 
S u bj ects will t a k e m oli n d o n e hy dr oc hl ori d e ext e n d e d-r el e as e t a bl et ( S P N- 8 1 0) or pl ac e b o t wic e e ac h 
d a y ( BI D) wit h or wit h o ut f o o d, i n t h e m or ni n g a n d i n t h e ev e ni n g, i n a d diti o n t o t h e st a bl e d os e of t h e 
o pti miz e d A D H D m e dic ati o n d et er mi n e d fr o m t h e l e a d-i n p eri o d.  If i niti ati n g tr e at m e nt b ef or e n o o n, 
p ati e nts s h o ul d st art wit h t h e m or ni n g d os e; if aft er n o o n, t h e e v e ni n g d os e. 
S u bj ects will b e r a n d o miz e d t o o n e of t hr e e tr e at m e nts at Visit 3.  S u bj ects will b e titr at e d u p t o t h e fi n al 
r a n d o miz e d t ot al d ail y d os e ( T D D).   
 
R ef er e nc e tr e at m e nt 
o  Tr e at m e nt 1: Pl ac e b o t a bl ets, P O, BI D 
 
T est tr e at m e nts  
o  Tr e at m e nt 2: M oli n d o n e ext e n d e d- r el e as e t a bl ets, 1 8 m g T D D, P O, BI D 
o  Tr e at m e nt 3: M oli n d o n e ext e n d e d-r el e as e t a bl ets, 3 6 m g T D D, P O, BI D 
 
4. 3. 2  
I d e ntit y of I n v esti g ati o n al Pr o d uct(s) 
T est a n d r ef er e nc e ( m atc hi n g pl ac e b o) pr o d ucts ar e eit h er p ur pl e ( 3 m g) or y ell o w ( 9 m g) r o u n d t a bl ets 
pri nt e d o n o n e si d e wit h t h e t a bl et d os e str e n gt h (“ 3 ” or “9 ”) t h at will b e s u p pli e d i n l a b el e d blist er 
c ar ds b y t h e S p o ns or. T h e S p o ns or will p ack a g e t h e S M i n a d o u bl e- bli n d c o nfi g ur ati o n.   

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 4 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
E ac h S M blist er c ar d will c o nt ai n c o m bi n ati o ns of m oli n d o n e ext e n d e d-r el e as e a n d/ or pl ac e b o t a bl ets, 
w hic h will s u p pl y a s u bj ect wit h 6 (six) t o 8 ( ei g ht) d a ys of d osi n g as w ell as s o m e extr as f or l ost pr o d uct 
a n d/ or t o acc o u nt f or visit d el a ys ass oci at e d wit h p ati e nt/sit e sc h e d ul es.  T h e S M blist er c ar d t y p es 
i ncl u d e: Titr ati o n (t w o blist er c ar ds), M ai nt e n a nc e (t hr e e blist er c ar ds), T a p er ( o n e blist er c ar d), a n d 
C o nv ersi o n ( o n e blist er c ar d).   
A si n gl e S M kit c o nt ai ns a t ot al of 7 pr e- p ack a g e d blist er c ar ds (t w o Titr ati o n blist er c ar ds, t hr e e 
M ai nt e n a nc e blist er c ar ds, o n e T a p eri n g blist er c ar d a n d o n e C o nv ersi o n blist er c ar d) a n d is m ar k e d wit h 
a u ni q u e 4- di git S M kit n u m b er.   
4. 3. 3  
St u d y M e dic ati o n H a n dli n g a n d Acc o u nt a bilit y 
All S M will b e s u p pli e d t o t h e I nv esti g at or b y t h e S p o ns or.  S M s u p pli es m ust b e k e pt i n a n a p pr o pri at e 
s ec ur e ar e a ( e. g., l oc k e d c a bi n et) a n d st or e d acc or di n g t o t h e c o n diti o ns s p ecifi e d o n t h e S M l a b els.  S M 
m ust b e st or e d b et w e e n 5 9 ° F –  8 6 ° F ( 1 5° C –  3 0 ° C). 
F oll o wi n g S p o ns or i nstr ucti o ns a n d i n c o m pli a nc e wit h I C H E 6 as w ell as l oc al, st at e, a n d f e d er al 
r e g ul ati o ns, t h e I nv esti g at or a n d st u dy st aff will b e r es p o nsi bl e f or t h e acc o u nt a bilit y of all cli nic al 
s u p pli es (r ec ei vi n g, s hi p m e nt, dis p e nsi n g, i n v e nt ory, a n d r ec or d k e e pi n g) i n a S M acc o u nt a bility l o g, a 
c o py of w hic h will b e c oll ect e d b y t h e S p o ns or at t h e e n d of t h e st u dy. 
U n d er n o circ u mst a nc es will t h e I nv esti g at or all o w t h e S M t o b e us e d ot h er t h a n as dir ect e d b y t his 
pr ot oc ol.  Cli nic al s u p pli es will n ot b e dis p e ns e d t o a ny i n di vi d u al w h o is n ot r a n d o miz e d i nt o t h e st u dy. 
A n acc ur at e a n d ti m el y r ec or d of t h e r ec ei pt of all cli nic al s u p pli es; dis p e nsi n g of S M t o t h e s u bj ect; 
c oll ecti o n of u n us e d s u p pli es r et ur n e d b y t h e s u bj ect; a n d s u bs e q u e nt r et ur n of u n us e d S M t o t h e 
S p o ns or m ust b e m ai nt ai n e d wit h d at es.  T his S M acc o u nt a bilit y l o g i ncl u d es, b ut m a y n ot b e li mit e d t o: 
( a) d oc u m e nt ati o n of r ec ei pt of cli nic al s u p pli es, ( b) S M i n v e nt ory l o g, (c) S M acc o u nt a bilit y l o g, a n d ( d) 
all s hi p pi n g s er vic e r ec ei pts.  All f or ms will b e pr ovi d e d b y t h e S p o ns or.  A ny c o m p ar a bl e f or ms t h at t h e 
st u dy sit e wis h es t o us e m ust b e a p pr o v e d b y t h e S p o ns or. 
T h e s u p pli es a n d i nv e nt or y r ec or ds m ust b e m a d e a v ail a bl e, u p o n r e q u est, f or i ns p ecti o n by t h e 
d esi g n at e d r e pr es e nt ati v e of t h e S p o ns or, a r e pr es e nt ati v e of t h e F D A, or a r e pr es e nt ativ e of a n o n- U S 
h e alt h a ut h orit y.  T h e assi g n e d Cli nic al R es e arc h Ass oci at e ( C R A) will r evi e w t h es e d oc u m e nts al o n g wit h 
all ot h er st u dy c o n d uct d oc u m e nts at e ac h a n d ev ery visit t o t h e st u dy sit e o nc e S M h as b e e n r ec ei v e d 
by t h e st u dy sit e.  All us e d, p artl y us e d, a n d u n us e d cli nic al s u p pli es, i ncl u di n g e m pt y c o nt ai n ers, ar e t o 
b e r et ur n e d t o t h e I nv esti g at or by t h e s u bj ect a n d ulti m at el y t o t h e S p o ns or at t h e c o ncl usi o n of t h e 
st u dy, u nl ess pr ovisi o n is m a d e by t h e S p o ns or f or d estr ucti o n of s u p pli es a n d c o nt ai n ers at t h e st u dy 
sit e.  U p o n c o m pl eti o n of S M acc o u nt a bility a n d r ec o ncili ati o n pr oc e d ur es b y st u dy sit e p ers o n n el a n d 
d oc u m e nt ati o n pr oc e d ur es b y S p o ns or p ers o n n el, S M is t o b e r et ur n e d t o t h e S p o ns or wit h a c o py of 
t h e c o m pl et e d S M dis p ositi o n f or m as o utli n e d i n t h e St u dy M e dic ati o n M a n u al. 
4. 3. 4  
M et h o d of Assi g ni n g S u bj ects t o Tr e at m e nt Gr o u ps 
All oc ati o n of st u dy dr u g will b e c o m pl et e d c e ntr ally t hr o u g h t h e us e of a n i nt er acti v e w e b r es p o ns e 
s yst e m (I W R S) t h at will d et er mi n e w hic h kit t o assi g n t o t h e s u bj ect. T h e r a n d o miz ati o n sc h e d ul es will 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
c o n d uct of t h e st u dy, a n d will n ot r ev e al t o a n y cli nic al p ers o n n el i n v ol v e d i n t h e st u dy t h e tr e at m e nt t o 
w hic h a s u bj ect is assi g n e d.    R a n d o miz ati o n sc h e d ul e d at a will b e k e pt strictl y c o nfi d e nti al, fil e d 
s ec ur el y b y t h e I W R S v e n d or, a n d acc essi bl e o nly t o a ut h oriz e d p ers o ns u ntil t h e ti m e of u n bli n di n g. 
T h e t est t a bl ets h av e m atc hi n g pl ac e b o t a bl ets.  T h e bli n d is m ai nt ai n e d pri m arily t hr o u g h t h e I W R S.  
T h e bli n d will b e m ai nt ai n e d t hr o u g h t h e e n d of t h e C o nv ersi o n/ T a p er p eri o d. 
T h e I nv esti g at or m ust tr y t o av oi d br e a ki n g t h e bli n d.  T h e d ec o di n g i nf or m ati o n will n ot b e vi e w e d 
u nl ess a n act u al m e dic al or m e dic ati o n s af et y e m er g e nc y occ urs.  T h e I nv esti g at or c a n acc ess t h e 
s u bj ect’s r a n d o miz e d tr e at m e nt i nf or m ati o n vi a I W R S o nl y if k n o wl e d g e of t h e tr e at m e nt r e gi m e n will 
i nfl u e nc e or assist wit h m e dic al m a n a g e m e nt of t h e s u bj ect i n a n ac ut e e m er g e nc y.  B ef or e br e aki n g t h e 
bli n d, e v ery eff ort m ust b e m a d e t o c o nt act t h e M e dic al M o nit or t o asc ert ai n t h e n ec essity of br e aki n g 
t h e c o d e.  If t h e I nv esti g at or is u ns ucc essf ul i n c o nt acti n g t h e M e dic al M o nit or, h e/s h e will c o nt act t h e 
b ac k u p M e dic al M o nit or ( or ot h er a p pr o pri at e d esi g n e e if t h e b ack u p M e dic al M o nit or is u n a v ail a bl e).  
If it is n ot p ossi bl e t o c o nt act t h e M e dic al M o nit or or t h e b ac k u p M e dic al M o nit or ( or d esi g n e e), a n d t h e 
sit u ati o n is a n e m er g e nc y, t h e I n v esti g at or m a y br e a k t h e bli n d a n d c o nt act t h e M e dic al M o nit or as 
s o o n as p ossi bl e.  T h e I nv esti g at or is t o m a k e a c ar ef ul n ot e of t h e d at e a n d ti m e of d ec o di n g, t h e r e as o n 
t h at n ec essit at e d br e aki n g t h e c o d e, a n d t h e si g n at ur e of t h e p ers o n w h o br ok e t h e c o d e.  U p o n 
br e a ki n g t h e r a n d o miz ati o n c o d e, t h e s u bj ect s h o ul d b e wit h dr a w n fr o m t h e st u dy b ut s h o ul d b e 
f oll o w e d u p f or s af ety p ur p os es. 
4. 4  Pr o hi bit e d M e dic ati o ns: 
S u bj ects m a y n ot b e o n a ny pr o hi bit e d m e dic ati o n w hil e o n st u dy as i n dic at e d i n t h e I ncl usi o n/ Excl usi o n 
Crit eri a. T h es e m e dic ati o ns i ncl u d e:  
 
α 2 - a dr e n er gic a g o nists ( e. g. cl o ni di n e a n d g u a nf aci n e) us e d f or a n y ot h er r e as o n exc e pt f or 
m o n ot h er a py tr e at m e nt f or A D H D  
 
A nti- ps yc h otics i ncl u di n g ari pi pr az ol e,  ris p eri d o n e, q u eti a pi n e, a n d zi pr asi d o n e  
 
A ntic o nv uls a nts i ncl u di n g c ar b a m az e pi n e a n d v al pr oic aci d, a nti d e pr ess a nts, m o o d st a biliz ers 
i ncl u di n g lit hi u m, b e nz o di az e pi n es, c h oli n est er as e i n hi bit ors or a ny dr u g k n o w n t o i n hi bit 
C Y P 2 D 6 acti vity 
 
H er b al s u p pl e m e nts 
4. 5  C o nc o mit a nt M e dic ati o n 
T h e d os e of t h e o n g oi n g A D H D m e dic ati o n wi ll n ot b e a dj ust e d d uri n g t h e st u dy, st arti n g at Visit 1. N o 
a d diti o n al c o nc o mit a nt m e dic ati o ns ar e all o w e d d uri n g t h e st u dy, wit h t h e f oll o wi n g exc e pti o ns: 
 
C hr o nic m e dic ati o n f or c o n diti o ns n ot r el at e d t o A D H D or I A t h at ar e all o w e d by I nv esti g at or at 
Scr e e ni n g 
 
N utriti o n al s u p pl e m e nts ( e. g. m ulti vit a mi ns, fis h oil) 
 
E ml a or ot h er n u m bi n g cr e a m f or P K v e ni p u nct ur e 
 
B e nztr o pi n e is p er mitt e d f or t h e tr e at m e nt of e m er gi n g E P S at a st arti n g d os e of 0. 5 m g BI D u p 
t o a r a n g e of 1 t o 4 m g/ d a y.  L or az e p a m ( 1 t o 2 m g p er d os e n ot t o exc e e d t hr e e ti m es d ail y) a n d 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
cl o n az e p a m ( 0. 2 5 t o 1 m g p er d os e n ot t o exc e e d t wic e d aily) will als o b e p er mitt e d t o tr e at 
e m er gi n g E P S.    
 
C o m m o n o v er-t h e-c o u nt er ( O T C) t h er a pi es f or mi n or tr a nsi e nt ail m e nts ( e. g. ac et a mi n o p h e n f or 
h e a d ac h e, i b u pr of e n f or f ev er) will b e all o w e d wit h o ut exc e pti o n. 
 
Tr e at m e nt f or A Es ot h er t h a n E P S or mi n or tr a nsi e nt ail m e nts is o nl y p er mitt e d i n c o ns ult ati o n 
wit h t h e M e dic al M o nit or.  
All c o nc o mit a nt m e dic ati o ns will b e r ec or d e d i n t h e e C R F. 
4. 6  C o m pl eti o n of St u d y a n d Disc o nti n u ati o n of S u bj ects  
S u bj ects will b e c o nsi d er e d t o h av e c o m pl et e d t h e st u dy if t h ey c o m pl et e all visits u p t o a n d i ncl u di n g 
Visit 6.  All s u bj ects w h o disc o nti n u e e arl y will c o m pl et e Visit 7.  A ny s u bj ect w h o disc o nti n u es fr o m t h e 
st u dy aft er Visit 5 will b e off er e d a T a p er kit.  
T h e I nv esti g at or(s) or s u bj ects t h e ms el v es m a y st o p S M tr e at m e nt at a ny ti m e f or s af ety or p ers o n al 
r e as o ns.  A s u bj ect is fr e e t o wit h dr a w fr o m t h e st u dy at a ny ti m e f or a n y r e as o n wit h o ut pr ej u dic e t o 
t h eir f ut ur e m e dic al c ar e by t h e p hysici a n or at t h e i nstit uti o n.  T h e I nv esti g at or or S p o ns or m ay als o 
wit h dr a w t h e s u bj ect at a ny ti m e i n t h e i nt er est of s u bj ect s af ety.  T h e wit h dr a w al of a s u bj ect fr o m t h e 
st u dy s h o ul d b e disc uss e d w h er e p ossi bl e wit h t h e M e dic al M o nit or a n d/ or C R A  b ef or e t h e s u bj ect st o ps 
S M.  S u bj ects r e m o v e d fr o m t h e st u dy f or a n y r e as o n will n ot b e r e pl ac e d. 
R e as o ns f or wit h dr a w al m ay i ncl u d e b ut ar e n ot li mit e d t o s u bj ect wit h dr a w al of c o ns e nt, occ urr e nc e of 
u n m a n a g e a bl e A Es, or if it is i n t h e b est i nt er est of t h e s u bj ect as p er I nv esti g at or’s discr eti o n . 
T h e pri m ar y r e as o n f or wit h dr a w al m ust b e r ec or d e d i n t h e s u bj ect’s m e dic al r ec or d a n d o n t h e e C R F.  If 
a s u bj ect is wit h dr a w n f or m or e t h a n o n e r e as o n, e ac h r e as o n s h o ul d b e d oc u m e nt e d i n t h e s o urc e 
d oc u m e nt a n d t h e m ost m e dic ally si g nific a nt  r e as o n s h o ul d b e e nt er e d o n t h e e C R F. 
5  A N AL Y SI S V A RI A BL E S 
5. 1  Pri m ar y Effic ac y V ari a bl e 
T h e pri m ar y effic acy e n d p oi nt will b e b as e d o n a c h ec klist of 1 5 I A b e h avi ors c oll ect e d i n a n el ectr o nic I A 
di ary.  T h e I A di ary c o m pris es t w o p arts:  1) A n e pis o dic di ary t h at will b e us e d b y t h e pri m ar y c ar e giv er 
( or alt er n at e) t o e nt er e v e nts as s o o n as p ossi bl e aft er t h e y ar e o bs erv e d; a n d 2) a n e v e ni n g di ary t h at 
will pr o m pt t h e c ar e giv er t o r evi e w ev e nts f or t h e d a y a n d t o e nt er a n y e v e nts t h at w er e n ot pr e vi o usl y 
c a pt ur e d.  Ev e nts c a n b e dir ectl y o bs er v e d b y t h e c ar e gi v er or c o ul d b e r e p ort e d t o t h e c ar e giv er by 
a n ot h er o bs erv er s uc h as a t e ac h er.   E ac h ev e nt will b e c h ar act eriz e d b y a c h ec klist of 1 5 o bs erv e d 
b e h a vi ors:  Y elli n g, Scr e a mi n g, T hr e at e ni n g, Scr atc hi n g, T hr o wi n g, Sl a m mi n g, Hitti n g S elf, Ar g ui n g, 
C ursi n g, N a m e C alli n g, S h ovi n g, H air P ulli n g, Fi g hti n g, Hitti n g Ot h ers, Kicki n g Ot h ers.  T h e c h ecklist will 
i n dic at e w h et h er e ac h b e h a vi or w as o bs er v e d (c o d e d 1) or w as n ot o bs erv e d (c o d e d 0) d uri n g t h e 
i nci d e nc e of a n ev e nt.  E ac h d a y c a n h av e m ulti pl e ev e nts.  A d ay c a n h av e n o e v e nt, as c a n b e att est e d 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
i n t h e ev e ni n g di ar y.  I n t his c as e, if n o ev e nt is r e p ort e d d uri n g a d a y, a n d t h e e v e ni n g di ar y c o nfir ms 
t his, t h e d aily ev e nt sc or e f or t h at s u bj ect will b e 0.  B e h a vi ors n ot o n t his list will n ot b e c a pt ur e d.   
5. 2  S ec o n d ar y Effic ac y V ari a bl es 
T h e f oll o wi n g effic acy sc al es will b e a d mi nist er e d at visits d esi g n at e d i n t h e Sc h e d ul e of Visits a n d 
Pr oc e d ur es ( T a bl e 1 ). 
5. 2. 1  
Cli nic al Gl o b al I m pr essi o n ( C GI) Sc al es 
T h e C GI sc al e w as d e v el o p e d t o pr ovi d e a bri ef, st a n d- al o n e ass ess m e nt of t h e cli nici a n’s vi e w of a 
s u bj ect’s gl o b al f u ncti o ni n g pri or t o a n d aft er a d mi nistr ati o n of a S M ( G uy 1 9 7 6).  S e v erit y of ill n ess ( C GI-
S) a n d gl o b al i m pr ov e m e nt ( C GI- I) ar e b ot h r at e d o n a sc al e of 1 t o 7 wit h 7 b ei n g “ extr e m ely ill” or “ v ery 
m uc h w ors e”, r es p ectiv el y.  S ucc essf ul t h er a py is i n dic at e d b y a l o w er ov er all sc or e i n s u bs e q u e nt 
t esti n g.  I nv esti g at ors s h o ul d c o nsi d er t h eir t ot al cli nic al ex p eri e nc e wit h c hil dr e n w h o h a v e I A c o m or bi d 
wit h A D H D a n d r at e h o w s e v er e t h e s u bj ect’s c o n diti o n is at t h e ti m e.   
 
C GI - S will b e e v al u at e d b y t h e I nv esti g at or at e ac h visit o n a 7- p oi nt sc al e wit h 1 = N or m al,    
2 = B or d erli n e ill, 3 = Mil dl y ill, 4 = M o d er at el y ill, 5 = M ark e dly ill, 6 = S ev er el y ill, a n d 7 = Extr e m ely ill.    
 
C GI -I, r el ativ e t o t h e c o n diti o n at Visit 3, will b e ev al u at e d b y t h e c ar e gi v er a n d b y t h e 
I nv esti g at or at e ac h p ost- b as eli n e visit o n a 7- p oi nt sc al e wit h 1 = V er y m uc h i m pr o v e d, 2 = M uc h 
i m pr ov e d, 3 = Mi ni m ally i m pr o v e d, 4 = N o c h a n g e, 5 = Mi ni m ally w ors e, 6 = M uc h w ors e, a n d 7 = V ery 
m uc h w ors e.    
C GI - S will b e ass ess e d b y t h e I nv esti g at or at Visit 1, Visit 3, Visit 4, Visit 5 a n d Visit 6.  C GI-I will b e 
ass ess e d b y t h e c ar e giv er a n d t h e I nv esti g at or at Visit 4, Visit 5 a n d Visit 6.   
5. 2. 2  
S w a ns o n, N ol a n, P el h a m R ati n g Sc al e- R e vis e d ( S N A P-I V) 
T h e S N A P-I V r ati n g sc al e i ncl u d es 1 8 A D H D a n d 8 o p p ositi o n al d efi a nt dis or d er ( O D D) sy m pt o ms as 
s p ecifi e d i n t h e D S M-I V- T R a n d I nt er n ati o n al St atistic al Cl assific ati o n of Dis e as es a n d H e alt h R el at e d 
Pr o bl e ms 1 0t h R e visi o n (I C D- 1 0) Cl assific ati o n of M e nt al a n d B e h avi or al Dis or d ers.  T h e s y m pt o ms ar e 
sc or e d b y assi g ni n g a s ev erit y esti m at e f or e ac h s y m pt o m o n a 4- p oi nt sc al e ( S w a ns o n 2 0 0 1).  T h e S N A P-
I V r ati n g s h o ul d b e p erf or m e d by t h e s a m e p ar e nt or l e g al r e pr es e nt ati v e at e ac h visit w h e n p ossi bl e. 
T h e r ati n gs fr o m t h e S N A P-I V sc al e ar e gr o u p e d i nt o t h e f oll o wi n g 4 s u bsc al es:   
 
A D H D-I n att e nti o n (it e ms # 1- 9),  
 
A D H D- Hy p er activity/I m p ulsivit y (it e ms # 1 0- 1 8)  
 
O D D (it e ms # 1 9- 2 6)   
 
A D H D- C o m bi n e d s u bsc al e: t h e first t w o s u bsc al e it e ms ar e c o m bi n e d   
E ac h s u bsc al e sc or e is t h e av er a g e of t h e sc or es i ncl u d e d i n t h e s u bsc al e. 
T h e S N A P-I V r ati n g sc al e will b e a d mi nist er e d at Visit 3 a n d Visit 6. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
5. 2. 3  
C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8- It e m ( C H Q- P F 2 8) 
T h e C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8-it e m ( C H Q- P F 2 8) is a s h ort g e n eric m e as ur e of h e alt h 
st at us a n d h e alt h r el at e d q u alit y of lif e (L a n d gr af 1 9 9 6).  C H Q- P F 2 8 it e ms h a v e f o ur, fi v e, or six r es p o ns e 
o pti o ns, di vi d e d ov er ei g ht m ulti-it e m sc al es ( p hysic al f u ncti o ni n g, g e n er al b e h avi or, m e nt al h e alt h, s elf-
est e e m, g e n er al h e alt h p erc e pti o ns, p ar e nt al i m p act: e m oti o n al, p ar e nt al i m p act: ti m e, a n d f a mily 
acti viti es) a n d fiv e si n gl e it e m c o nc e pts (r ol e f u ncti o ni n g: e m oti o n al/ b e h a vi or, r ol e f u ncti o ni n g: p hysic al, 
b o dily p ai n, f a mily c o h esi o n, a n d c h a n g e i n h e alt h). T h e C H Q- P F 2 8 s h o ul d b e p erf or m e d b y t h e pri m ary 
c ar e giv er w h e n p ossi bl e.   
T h e C H Q- P F 2 8 will b e a d mi nist er e d at Visit 3 a n d Visit 6. 
5. 2. 4  
P ar e nti n g Str ess I n d e x- S h ort F or m ( P SI- 4- S F) 
R e d ucti o n i n str ess is c o nsi d er e d i m p ort a nt f or p ar e nts of c hil dr e n wit h disr u pti v e b e h a vi or pr o bl e ms, 
d e v el o p m e nt al dis a biliti es, a n d c hr o nic ill n ess ( H as k ett 2 0 0 6).  T h e P ar e nti n g Str ess I n d ex –  S h ort F or m 
( P SI- 4- S F) is a 3 6-it e m s elf-r e p ort m e as ur e of p ar e nti n g str ess ( A bi di n 1 9 9 5). T hr e e s u bsc al es ( P ar e nt al 
Distr ess, P ar e nt- C hil d D ysf u ncti o n al I nt er acti o n, a n d Diffic ult C hil d) c o nsist of 1 2 it e ms e ac h.  P ar e nts 
us e a 5- p oi nt sc al e t o i n dic at e t h e d e gr e e t o w hic h t h e y a gr e e wit h e ac h st at e m e nt.   
T h e P SI- 4- S F will b e a d mi nist er e d at Visit 3 a n d Visit 6. 
5. 3  P h ar m ac o ki n etic M e as ur e m e nts 
 
 
 
 
5. 3. 1  
P h ar m ac o ki n etic V ari a bl es 
T h e p h ar m ac o ki n etic v ari a bl es ar e: 
 
A p p ar e nt cl e ar a nc e ( CL/ F) of m oli n d o n e i n t h e p e di atric p o p ul ati o n 
 
A p p ar e nt v ol u m e of distri b uti o n ( V/ F) of m oli n d o n e i n p e di atric p o p ul ati o n 
 
Eff ect o n m oli n d o n e a p p ar e nt cl e ar a nc e ( CL/ F) of c o- a d mi nistr ati o n of a m p h et a mi n es, 
m et hyl p h e ni d at e, cl o ni di n e, g u a nf aci n e a n d at o m ox eti n e  
5. 3. 2  
E x pl or at or y P h ar m ac o ki n etic V ari a bl es 
 
 
 
 
 
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
5. 4  S af et y Ass ess m e nts 
S af et y ass ess m e nts will c o nsist of m o nit ori n g of a n d r ec or di n g of all c o nc o mit a nt m e dic ati o ns a n d A Es, 
cli nic al l a b or at ory t ests, m e as ur e m e nt of vit al si g ns a n d 1 2-l e a d E C Gs, s uici d alit y m o nit ori n g, a n d t h e 
p erf or m a nc e of p hysic al ex a mi n ati o ns at visits d esi g n at e d i n t h e Sc h e d ul e of Visits a n d Pr oc e d ur es 
(T a bl e 1 ). 
Ass ess m e nt of p ossi bl e n e ur ol o gic al si d e eff ects a n d E P S will b e p erf or m e d usi n g t h e Si m ps o n- A n g us 
sc al e, t h e B ar n es A k at hisi a sc al e a n d t h e AI M S.  A p ositi v e r ati n g or fi n di n g o n t h e s af ety sc al e will b e 
c a pt ur e d as a n A E at t h e discr eti o n of t h e I nv esti g at or. 
5. 4. 1  
A d v ers e E v e nts 
As d efi n e d b y t h e I C H G ui d eli n e f or G C P, a n a d v ers e e v e nt ( A E)  is a ny u nt o w ar d m e dic al occ urr e nc e i n a 
p ati e nt or cli nic al i nv esti g ati o n s u bj ect a d mi nist er e d a p h ar m ac e utic al pr o d uct a n d w hic h d o es n ot 
n ec ess arily h a v e t o h av e a c a us al r el ati o ns hi p wit h tr e at m e nt. 
A n A E c a n b e: 
 
A ny u nf a v or a bl e a n d u ni nt e n d e d si g n (i ncl u di n g a n a b n or m al l a b or at ory fi n di n g), s y m pt o m, or 
dis e as e t e m p or ally ass oci at e d wit h t h e us e of a m e dici n al pr o d uct, w h et h er or n ot c o nsi d er e d 
r el at e d t o t h e m e dici n al pr o d uct. 
 
A ny n e w dis e as e, i nt erc urr e nt i nj uri es, or ex ac er b ati o n of a n existi n g dis e as e. 
 
A ny d et eri or ati o n i n a l a b or at ory v al u e or ot h er cli nic al t est ( e. g., E C G) t h at r es ults i n s y m pt o ms, 
a c h a n g e i n tr e at m e nt, or disc o nti n u ati o n fr o m S M. 
 
R ec urr e nc e of a n i nt er mitt e nt m e dic al c o n diti o n ( e. g., h e a d ac h e) n ot pr es e nt at b as eli n e. 
S ur gic al pr oc e d ur es ar e n ot A Es; t h ey ar e t h er a p e utic m e as ur es f or c o n diti o ns t h at r e q uir e s ur g er y.  T h e 
c o n diti o n f or w hic h t h e s ur g er y is r e q uir e d is a n A E, if it occ urs or is d et ect e d d uri n g t h e st u dy p eri o d. 
5. 4. 1. 1  C a us alit y 
A Es m ay b e c at e g oriz e d as eit h er A dv ers e Dr u g R e acti o ns or S us p ect e d A dv ers e Dr u g R e acti o ns b as e d 
o n t h eir r el ati o ns hi p t o S M a n d t h e d e gr e e of c ert ai nty a b o ut c a us alit y.  
S us p ect e d a d v ers e dr u g r e acti o ns  ( S A D Rs) ar e a s u bs et of a d v ers e ev e nts f or w hic h t h er e is evi d e nc e t o 
s u g g est a c a us al r el ati o ns hi p b et w e e n t h e dr u g a n d t h e A E, i. e., t h er e is a r e as o n a bl e p ossi bility t h at t h e 
dr u g c a us e d t h e a dv ers e e v e nt.   
A d v ers e dr u g r e acti o ns  ( A D Rs) ar e a s u bs et of all S A D Rs f or w hic h t h er e is r e as o n t o c o ncl u d e t h at t h e 
dr u g c a us e d t h e e v e nt. 
5. 4. 1. 2  R ec or di n g a n d E v al u ati o n of A d v ers e E v e nts 
All s u bj ects w h o ar e e nr oll e d (st arti n g at Visit 3) will b e q u esti o n e d r e g ar di n g t h e occ urr e nc e of A Es.  At 
e ac h c o nt act wit h t h e s u bj ect, t h e i n v esti g at or m ust s e e k i nf or m ati o n o n A Es by s p ecific q u esti o ni n g 
a n d, as a p pr o pri at e, by ex a mi n ati o n.  I nf or m ati o n o n all A Es s h o ul d b e r ec or d e d i m m e di at ely i n t h e 
s o urc e d oc u m e nt, a n d als o i n t h e a p pr o pri at e a dv ers e e v e nt m o d ul e of t h e e C R F.  All cl e arly r el at e d 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
si g ns, s y m pt o ms, a n d a b n or m al di a g n ostic pr oc e d ur es r es ults s h o ul d b e r ec or d e d i n t h e s o urc e 
d oc u m e nt, t h o u g h t h ey m ay b e gr o u p e d u n d er o n e di a g n osis.  F or ex a m pl e, f ev er, el ev at e d W B C, c o u g h, 
a b n or m al c h est X- r ay, etc., c a n all b e r e p ort e d as “ p n e u m o ni a”. 
All A Es occ urri n g aft er e nr oll m e nt a n d t hr o u g h o ut t h e st u dy p eri o d m ust b e r ec or d e d.  A tr e at m e nt-
e m er g e nt a dv ers e ev e nt ( T E A E) is d e fi n e d as a n A E wit h a st art d at e o n or aft er t h e first d os e of st u dy 
dr u g, or t h at w ors e n e d f oll o wi n g first a d mi nistr ati o n of st u dy dr u g. F or s u bj ects w h o r ec eiv e S M, T E A Es 
will b e c oll ect e d st arti n g fr o m t h e first d os e of S M.  T h e cli nic al c o urs e of e ac h A E s h o ul d b e f oll o w e d 
u ntil r es ol uti o n or u ntil, i n t h e m e dic al j u d g m e nt of t h e I nv esti g at or, t h e ev e nt h as st a biliz e d or is 
ass ess e d as c hr o nic.   
A n i ncr e as e i n t h e C S S R S, Si m ps o n A n g us Sc al e, B ar n es A k at hisi a Sc al e, or t h e AI M S will n ot n ec ess arily 
b e r at e d as a n A E u nl ess t h e ev e nt m e ets A E crit eri a. 
T h e I nv esti g at or is r es p o nsi bl e f or e v al u ati n g A Es a n d d et er mi ni n g t h e f oll o wi n g: 
 
S eri o us vs. N o n-s eri o us:  Is t h e ev e nt a S eri o us A dv ers e E v e nt ( S A E) ? 
 
C a us alit y:  W as A E r el at e d or p ossi bl y r el at e d t o t h e S M ? 
 
S e v erit y:  H o w pr o n o u nc e d is t h e i nc a p acit y/ disc o mf ort c a us e d by a n A E ? 
5. 4. 1. 3  Crit eri a f or Ass essi n g S e v erit y 
T h e I nv esti g at or will ev al u at e t h e c o m m e nts of t h e s u bj ect a n d t h e r es p o ns e t o tr e at m e nt i n or d er t h at 
h e or s h e m a y j u d g e t h e tr u e n at ur e a n d s e v erity of t h e A E.  S ev erit y r ef ers t o t h e acc u m ul at e d i nt e nsity 
of disc o mf ort/i m p air m e nt of h e alt h si nc e t h e l ast r ec or di n g of A Es a n d will b e ass ess e d acc or di n g t o t h e 
f oll o wi n g crit eri a: 
 
Mil d:   A w ar e n ess of si g n, sy m pt o m, or e v e nt, b ut e asil y t ol er at e d 
 
M o d er at e : Disc o mf ort e n o u g h t o i nt erf er e wit h us u al acti vity a n d m ay w arr a nt i nt er v e nti o n 
 
S e v er e:  I nc a p acit ati n g wit h i n a bility t o d o us u al acti viti es or si g nific a ntl y aff ects cli nic al st at us 
a n d w arr a nts i nt er v e nti o n 
T h e crit eri a f or ass essi n g s ev erity ar e diff er e nt fr o m t h os e us e d f or s eri o us n ess. 
5. 4. 1. 4  Crit eri a f or Ass essi n g C a us alit y 
T h e I nv esti g at or is r es p o nsi bl e f or d et er mi ni n g t h e r el ati o ns hi p b et w e e n t h e a d mi nistr ati o n of S M a n d 
t h e occ urr e nc e of a n A E as n ot s us p ect e d  or as a s us p ect e d r e acti o n t o S M.  T h es e ar e d efi n e d as 
f oll o ws: 
N ot s us p ect e d:  T h e t e m p or al r el ati o ns hi p of t h e A E t o S M a d mi nistr ati o n m a k es a c a us al r el ati o ns hi p 
u nli k el y , or ot h er dr u gs, t h er a p e utic i nt er v e nti o ns, or u n d erl yi n g c o n diti o ns pr o vi d e a s uffici e nt 
ex pl a n ati o n f or t h e o bs erv e d e v e nt.  
 
N ot r el at e d:   T e m p or al r el ati o ns hi p t o S M a d mi nistr ati o n is missi n g or i m pl a usi bl e, or t h er e is a n 
e vi d e nt ot h er c a us e. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
U nli k el y r el at e d :  T e m p or al r el ati o ns hi p t o S M a d mi nistr ati o n m ak es a c a us al r el ati o ns hip 
i m pr o b a bl e; a n d ot h er dr u gs, c h e mic als, or u n d erlyi n g dis e as e pr o vi d e pl a usi bl e ex pl a n ati o ns. 
S us p ect e d:  T h e t e m p or al r el ati o ns hi p of t h e A E t o S M a d mi nistr ati o n m a k es a c a us al r el ati o ns hi p 
p ossi bl e , a n d ot h er dr u gs, t h er a p e utic i nt erv e nti o ns, or u n d erl yi n g c o n diti o ns d o n ot pr o vi d e a s uffici e nt 
ex pl a n ati o n f or t h e o bs erv e d e v e nt.  
 
P ossi bl y r el at e d:   T e m p or al r el ati o ns hi p t o S M a d mi nistr ati o n is pl a usi bl e, b ut c o nc urr e nt 
dis e as e or ot h er dr u gs or c h e mic als c o ul d als o ex pl ai n e v e nt.  I nf or m ati o n o n dr u g wit h dr a w al 
m a y b e l acki n g or u ncl e ar.  T his will b e r e p ort e d as a S us p ect e d A d v ers e Dr u g R e acti o n ( S A D R) . 
 
D efi nit el y r el at e d:  T e m p or al r el ati o ns hi p t o S M a d mi nistr ati o n is pl a usi bl e, a n d c o nc urr e nt 
dis e as e or ot h er dr u gs or c h e mic als c a n n ot ex pl ai n e v e nt.   T h e r es p o ns e t o wit h dr a w al of t h e 
m e dic ati o n ( d ec h all e n g e) s h o ul d b e cli nic ally pl a usi bl e.   T h e e v e nt m ust b e d efi niti v e 
p h ar m ac ol o gic ally or p h e n o m e n ol o gic all y, usi n g a s atisf act ory r ec h all e n g e pr oc e d ur e if 
n ec ess ary.   T his will b e r e p ort e d as a n A d v ers e Dr u g R e acti o n ( A D R). 
5. 4. 2  
S eri o us A d v ers e E v e nts ( S A E) 
A Es ar e cl assifi e d as s eri o us or n o n-s eri o us.  A n A E or A D R is c o nsi d er e d “s eri o us” if, i n t h e vi e w of eit h er 
t h e i n v esti g at or or S p o ns or, it r es ults i n o n e of t h e f oll o wi n g o utc o m es:  
 
d e at h 
 
lif e-t hr e at e ni n g A E (i. e., t h e s u bj ect w as at i m m e di at e ris k of d e at h fr o m t h e A E as it occ urr e d.  
T his d o es n ot i ncl u d e a n e v e nt t h at, h a d it occ urr e d i n a m or e s ev er e f or m or w as all o w e d t o 
c o nti n u e, mi g ht h av e c a us e d d e at h.) 
 
i n- p ati e nt h os pit aliz ati o n or pr ol o n g ati o n of existi n g h os pit aliz ati o n 
 
p ersist e nt or si g nific a nt dis a bilit y or i nc a p acity or s u bst a nti al disr u pti o n of t h e a bilit y t o c o n d uct 
n or m al lif e f u ncti o ns 
 
a c o n g e nit al a n o m aly or birt h d ef ect 
 
a n i m p ort a nt m e dic al ev e nt 
I m p ort a nt m e dic al e v e nts ar e t h os e t h at m a y n ot b e i m m e di at ely lif e t hr e at e ni n g or r es ult i n d e at h or 
h os pit aliz ati o n, b ut ar e cl e arly of m aj or cli nic al si g nific a nc e.   T h ey m a y j e o p ar diz e t h e s u bj ect, a n d m ay 
r e q uir e i nt erv e nti o n t o pr ev e nt o n e of t h e ot h er s eri o us o utc o m es n ot e d a b ov e.  F or ex a m pl e, dr u g 
d e p e n d e nc e or a b us e, bl o o d d yscr asi as, a s eiz ur e t h at di d n ot r es ult i n i n- p ati e nt h os pit aliz ati o n, or 
i nt e nsi v e tr e at m e nt f or all er gic br o nc h os p as m i n a n e m er g e nc y d e p art m e nt w o ul d t y pic ally b e 
c o nsi d er e d s eri o us. 
5. 4. 2. 1  I n v esti g at or R es p o nsi biliti es f or R e p orti n g S A Es 
T h e I nv esti g at or m ust i m m e di at el y r e p ort t o t h e S p o ns or all S A Es, r e g ar dl ess of w h et h er t h e I nv esti g at or 
b eli e v es t h ey ar e dr u g r el at e d. 
All S A Es m ust b e r e p ort e d t o t h e Dr u g S af et y C o nt act wit hi n 2 4 h o urs of first b ec o mi n g a w ar e of t h e 
S A E.  T h e I nv esti g at or m ust c o m pl et e a n S A E e C R F i n E D C a n d i ncl u d e a d et ail e d d escri pti o n of t h e S A E, 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
as w ell as ot h er a v ail a bl e i nf or m ati o n p erti n e nt t o t h e c as e ( e. g., h os pit al r ec or ds, a ut o psy r e p orts a n d 
ot h er r el ev a nt d oc u m e nts).  S h o ul d t h e sit e b e u n a bl e t o acc ess E D C, a p a p er S A E f or m m ust b e 
c o m pl et e d a n d s e nt t o  
Dr u g S af et y b y e m ail or f ax. T h e i nv esti g at or will k e e p a c o py of t his S A E 
R e p ort f or m o n fil e at t h e st u dy sit e. O nc e E D C b ec o m es a v ail a bl e, t h e sit e m ust c o m pl et e t h e S A E e C R F 
i n E D C.  
T h e I nv esti g at or or st u dy p hysici a n, aft er t h or o u g h c o nsi d er ati o n of all f acts t h at ar e a v ail a bl e, m ust 
i ncl u d e a n ass ess m e nt of c a us alit y of a n A E t o S M i n t h e r e p ort t o t h e S p o ns or.   
F oll o w- u p i nf or m ati o n, or n e w i nf or m ati o n av ail a bl e aft er t h e i niti al r e p ort, s h o ul d b e activ el y s o u g ht 
a n d r e p ort e d t o t h e S p o ns or as it b ec o m es a v ail a bl e usi n g t h e S A E R e p ort F or m.   
T h e Dr u g S af ety C o nt act f or S A E r e p orti n g is: 
 
 
 
 
 
5. 4. 2. 2  Ot h er E v e nts R e q uiri n g I m m e di at e R e p orti n g 
T h e I nv esti g at or m ust r e p ort a pr e g n a nc y  t h at occ urs i n a s u bj ect d uri n g a cli nic al st u dy t o t h e Dr u g 
S af et y C o nt act wit hi n 2 4 h o urs of first b ec o mi n g a w ar e of t h e e v e nt.   Pr e g n a ncy s h o ul d b e r e p ort e d o n a 
Pr e g n a nc y R e p ort F or m.   T h e I nv esti g at or s h o ul d disc uss t h e c as e wit h t h e M e dic al M o nit or; t h e 
I nv esti g at or m ust f oll o w a ny pr e g n a nt s u bj ect f or 3 m o nt hs aft er t h e c hil d is b or n.  T h e I nv esti g at or 
m ust c o m pl et e a Pr e g n a nc y O utc o m e F or m as a f oll o w u p. A ny A E s c o nc er ni n g t h e pr e g n a nc y of t h e 
s u bj ect d uri n g pr e g n a nc y or t h e c hil d aft er birt h m ust b e d oc u m e nt e d a n d r e p ort e d t o t h e S p o ns or. 
Tr e at m e nt- e m er gi n g E P S  ( e. g. a k at hisi a, dyst o ni a, P arki ns o nis m, t ar div e d ys ki n esi a) a n d n e ur ol e ptic 
m ali g n a nt sy n dr o m e s h o ul d b e r e p ort e d t o t h e Dr u g S af et y C o nt act p ers o n(s) by c o m pl eti n g t h e A dv ers e 
E v e nt of S p eci al I nt er est ( A E SI) e C R F i n E D C.  S h o ul d t h e sit e b e u n a bl e t o acc ess E D C, a p a p er A E SI f or m 
m ust b e c o m pl et e d a n d s e nt t o  
 Dr u g S af ety b y e m ail or f ax wit hi n 2 4 h o urs of first b ec o mi n g a w ar e 
of t h e ev e nt.   O nc e E D C b ec o m es a v ail a bl e t h e sit e m ust c o m pl et e A E SI e C R F i n E D C. E P S i nci d e nc e will 
b e s u m m ariz e d a n d s h ar e d wit h st u dy I nv esti g at ors t hr o u g h o ut t h e tri al.   
O v er d os a g e  of m oli n d o n e pr es u m a bl y m a y b e m a nif est e d b y s ev er e E P S a n d s e d ati o n.  C o m a wit h 
r es pir at ory d e pr essi o n a n d s e v er e hy p ot e nsi o n r es ulti n g i n a s h ock-li k e s y n dr o m e c o ul d occ ur. I n t he 
e v e nt of a s us p ect e d ov er d os e, t h e p ar e nt or l e g al r e pr es e nt ativ e s h o ul d b e i nstr uct e d t o c all 9 1 1 or 
t h eir l oc al p ois o n c o ntr ol c e nt er at 
. 
S y m pt o m atic, s u p p ortiv e t h er a py s h o ul d b e t h e r ul e.  G astric l av a g e is i n dic at e d f or t h e r e d ucti o n of 
a bs or pti o n of m oli n d o n e w hic h is fr e ely s ol u bl e i n w at er. Si nc e t h e a ds or pti o n of m oli n d o n e by 
acti v at e d c h arc o al h as n ot b e e n d et er mi n e d, t h e us e of t his a nti d ot e m ust b e c o nsi d er e d of t h e or etic al 
v al u e. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 5 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
E m esis i n a c o m at os e p ati e nt is c o ntr ai n dic at e d. A d diti o n ally, w hil e t h e e m etic eff ect of a p o m or p hi n e is 
bl oc k e d b y m oli n d o n e i n a ni m als, t his bl ocki n g eff ect h as n ot b e e n d et er mi n e d i n h u m a ns. 
5. 4. 2. 3  S p o ns or R es p o nsi biliti es f or E x p e dit e d R e p orti n g of S A Es 
T h e S p o ns or will i nf or m I nv esti g at ors a n d r e g ul at ory a ut h oriti es of r e p ort a bl e e v e nts, i n c o m pli a nc e 
wit h a p plic a bl e r e g ul at ory r e q uir e m e nts, o n a n ex p e dit e d b asis (i. e., wit hi n s p ecific ti m efr a m es).  F or 
t his r e as o n, it is i m p er ativ e t h at st u dy sit es s u b mit S A E i nf or m ati o n t o t h e S p o ns or i n t h e m a n n er 
d escri b e d a b o v e.  
I nv esti g at ors m ust c o m ply wit h t h e a p plic a bl e r e g ul at or y r e q uir e m e nts r el at e d t o t h e r e p orti n g of S A Es 
t o t h e I R B/I E C.  I nv esti g at ors m ust als o s u b mit t h e s af et y i nf or m ati o n pr ovi d e d by t h e S p o ns or t o t h e 
I R B/I E C u nl ess t h e c o u ntr y l e g al r e g ul ati o n r e q uir es t h at t h e S p o ns or s h o ul d b e r es p o nsi bl e f or t h e 
s af et y r e p orti n g t o t h e I R B/I E C. 
It is t h e r es p o nsi bilit y of t h e S p o ns or t o n otif y all p artici p ati n g i n v esti g at ors, i n a writt e n I N D s af ety 
r ep ort, of a n y S A D R t h at is b ot h s eri o us a n d u n ex p ect e d.  T h e S p o ns or will als o n otif y p artici p ati n g 
i nv esti g at ors of a ny fi n di n gs fr o m ot h er s o urc es ( ot h er st u di es, a ni m al a n d i n vitr o t esti n g, etc.) t h at 
s u g g est a si g nific a nt ris k f or h u m a n s u bj ects.  S uc h fi n di n gs will t y pic ally l e a d t o s af et y-r el at e d c h a n g es 
i n t h e st u dy pr ot oc ol, I nf or m e d C o ns e nt, a n d/ or I nv esti g at or’s Br oc h ur e. 
5. 4. 3  
M a n a g e m e nt of Tr e at m e nt- E m er gi n g E P S 
If a s u bj ect ex p eri e nc es tr e at m e nt- e m er gi n g E P S (i ncl u di n g a k at hisi a, dyst o ni a, P ar ki ns o nis m, or t ar di v e 
dys ki n esi a), b e nztr o pi n e will b e p er mitt e d at a st arti n g d os e of 0. 5 m g BI D u p t o a r a n g e of 1 t o 
4 m g/ d a y.  L or az e p a m ( 1 t o 2 m g p er d os e n ot t o exc e e d t hr e e ti m es d ail y) a n d cl o n az e p a m ( 0. 2 5 t o 1 
m g p er d os e n ot t o exc e e d t wic e d ail y) will als o b e p er mitt e d t o tr e at e m er gi n g E P S. 
A p ositiv e fi n di n g o n a n E P S s af ety ass ess m e nt sc al e ( B ar n es A k at hisi a, Si m ps o n- A n g us, AI M S) d o es n ot 
n ec ess arily e q u at e t o a n E P S e v e nt.  I nv esti g at ors s h o ul d e v al u at e p ositi v e fi n di n gs o n t h e E P S s af et y 
ass ess m e nt sc al es a n d i nt e gr at e t h e m i nt o a gl o b al cli nic al o bs erv ati o n t o d et er mi n e if a n A E of E P S 
s h o ul d b e r ec or d e d. 
5. 4. 4  
L a b or at or y M e as ur e m e nts 
Wit h t h e exc e pti o n of uri n e pr e g n a nc y t est, cli nic al l a b or at or y t ests will b e p erf or m e d by a c e ntr al 
l a b or at or y as s p ecifi e d i n t h e r ef er e nc e bi n d er. 
D et ails f or c oll ecti n g, h a n dli n g, a n d s hi p pi n g s a m pl es (i ncl u di n g s hi p m e nt a d dr ess es) will b e d et ail e d i n a 
s e p ar at e l a b or at ory m a n u al.  T h e Sc h e d ul e of Visits a n d Pr oc e d ur es ( T a bl e 1 ) s h o ws t h e ti m e p oi nts at 
w hic h uri n e s a m pl es will b e c oll ect e d f or uri n al ysis a n d bl o o d s a m pl es will b e c oll ect e d f or cli nic al 
l a b or at or y t ests a n d pl as m a c o nc e ntr ati o n l ev els.   
T a bl e 3  pr es e nts t h e cli nic al l a b or at or y t ests t o b e p erf or m e d.  M et a b olic p ar a m et ers (i ncl u di n g i ns uli n, 
gl uc os e, tri gl yc eri d es, a n d c h ol est er ol) a n d pr ol acti n will b e m e as ur e d. A s u bj ect will b e excl u d e d if t h e 
Scr e e ni n g bl o o d t est r es ults i n dic at es > 2 ti m es t h e u p p er li mit of n or m al ( UL N) of al a ni n e 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
a mi n otr a nsf er as e ( AL T), as p art at e a mi n otr a nsf er as e ( A S T), g a m m a gl ut a myl tr a ns p e pti d as e ( G G T), 
a n d/ or s er u m cr e ati ni n e. L a b or at or y t ests will n ot b e r e p e at e d f or t h es e s u bj ects. 
All l a b or at or y t ests will b e r e vi e w e d i n a ti m ely m a n n er b y q u alifi e d sit e p ers o n n el t o e ns ur e s af ety.  
A b n or m al l a b fi n di n gs m ay b e c o nfir m e d if n ec ess ary by o n e r e p e at e d t esti n g at t h e discr eti o n of t h e 
I nv esti g at or.  A ny r e p e at l a b or at or y t esti n g will b e c o n d uct e d u n d er f asti n g c o n diti o n. A ny l a b or at or y 
a b n or m alit y m ay q u alif y as a n A E i n t h e I nv esti g at or’s j u d g m e nt.  
A t ot al of a p pr oxi m at el y 4 2 mL of bl o o d p er s u bj ect will b e dr a w n d uri n g t h e st u dy: 2 2 mL is f or cli nic al 
l a b or at or y t ests a n d 2 0 mL is f or P K s a m pli n g. 
 
T a bl e 3: Cli nic al L a b or at or y T ests 
C at e g or y  
P ar a m et ers  
H e m at ol o gy  
R B C , W B C, H g b, H C T, M C H, M C H C, M C V, pl at el et c o u nt, a n d W B C wit h 
diff er e nti al ( n e utr o p hils, l y m p h ocyt es, m o n ocyt es, e osi n o p hils, b as o p hils , 
l ar g e u nst ai n e d c ells) 
C h e mistr y  
 
 
 
El ectr ol yt es:  N a +, K+, c hl ori d e, bic ar b o n at e 
Li v er f u ncti o n t ests: al k ali n e p h os p h at as e, A S T, AL T, t ot al bilir u bi n, dir ect 
bilir u bi n  ,i n dir ect bilir u bi n 
R e n al f u ncti o n p ar a m et ers:  B U N, cr e ati ni n e  
Ot h er:  gl uc os e, C a + 2, al b u mi n, p h os p h or us, l act at e d e h y dr o g e n as e, t ot al 
pr ot ei n, C K/ C P K, gl o b uli n , uric aci d, tri gl yc eri d es, i ns uli n, pr ol acti n , 
c h ol est er ol –  t ot al, H DL a n d L DL  
A m yl as e, g a m m a G T ( G G T), Ir o n, Li p as e, M a g n esi u m  
Uri n e  
Uri n al ysis  
Uri n e Dr u g Scr e e n  
Uri n e pr e g n a ncy t est ( F O C B P o nl y)  
 
5. 4. 5  
Vit al Si g n a n d H ei g ht/ W ei g ht M e as ur e m e nts 
Vit al si g n m e as ur e m e nts ( e. g., bl o o d pr ess ur e, h e art r at e, t e m p er at ur e, a n d r es pir at ory r at e) a n d h ei g ht, 
w ei g ht a n d B MI will b e o bt ai n e d at visits d esi g n at e d o n t h e Sc h e d ul e of Visits a n d Pr oc e d ur es ( T a bl e 1 ).  
Bl o o d pr ess ur e a n d h e art r at e will b e m e as ur e d aft er t h e s u bj ect h as b e e n sitti n g f or 5 mi n ut es. Vit al 
si g ns m ay b e t a k e n at a ny ot h er ti m e, as d e e m e d n ec ess ar y b y t h e I nv esti g at or. 
5. 4. 6  
M e dic al Hist or y  
M e dic al hist ory will b e c oll ect e d at visits d esi g n at e d o n t h e Sc h e d ul e of Visits a n d Pr oc e d ur es ( T a bl e 1 ).   
5. 4. 7  
P h ysic al E x a mi n ati o ns a n d El ectr oc ar di o gr a ms ( E C Gs) 
A p hysic al ex a mi n ati o n a n d a 1 2 -l e a d E C G will b e o bt ai n e d at visits d esi g n at e d o n t h e Sc h e d ul e of Visits 
a n d Pr oc e d ur es ( T a bl e 1 ).  A d diti o n al E C Gs m ay b e p erf or m e d at ot h er ti m es if d e e m e d n ec ess ary b y t h e 
I nv esti g at or. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T h e E C G will b e r ec or d e d w hil e t h e s u bj ect is r esti n g i n a s u pi n e p ositi o n.  T h e E C G will el ectr o nic ally 
m e as ur e t h e P R, Q R S, Q T, a n d Q Tc i nt er v als, a n d h e art r at e. 
All E C G tr aci n gs will b e r evi e w e d wit hi n 2 4 h o urs b y t h e I nv esti g at or or q u alifi e d S u b -I nv esti g at or.  P R 
i nt er v als will b e d et er mi n e d f or e ac h of t h es e E C Gs fr o m a si n gl e r e a di n g.  I nv ali d m e as ur e m e nts will b e 
r e p e at e d.  Q Tc will b e r e p ort e d as Q Tc F ( Q T c orr ect e d usi n g Fri d erici a's m et h o d).  
5. 4. 8  
Ot h er S p eci al T ests 
T h e f oll o wi n g s p eci al t ests will b e a d mi nist er e d i n t h e cli nic at visits d esi g n at e d i n t h e Sc h e d ul e of Visits 
a n d Pr oc e d ur es ( T a bl e 1 ).   
5. 4. 8. 1  K- S A D S- PL 2 0 1 3 Di a g n ostic I nt er vi e w 
T h e K- S A D S- PL 2 0 1 3 is a s e mi-str uct ur e d di a g n ostic i nt er vi e w d esi g n e d t o di a g n os e c urr e nt a n d p ast 
e pis o d es of ps yc h o p at h ol o gy i n c hil dr e n a n d a d ol esc e nts acc or di n g t o D S M- 5 crit eri a ( K a uf m a n 1 9 9 7). 
W e will us e a v ersi o n of K- S A D S 2 0 1 3 t h at w as r evis e d t o b e c o m p ati bl e t o t h e D S M- 5 crit eri a.  It 
i ncl u d es  t h e p ar e nt a n d c hil d D S M- 5 cr oss-c utti n g s y m pt o ms m e as ur es  ( D S M- 5 C C- S M); a n 
u nstr uct ur e d I ntr o d uct ory I nt er vi e w; t h e Di a g n ostic Scr e e ni n g I nt ervi e w; t h e S u p pl e m e nt C o m pl eti o n 
C h ec klist; t h e Di a g n ostic S u p pl e m e nts a n d t h e S u m m ar y Lif eti m e Di a g n ostic C h ecklist.  T h e K- S A D S- PL 
2 0 1 3 will b e us e d at scr e e ni n g t o c o nfir m t h e di a g n osis of A D H D, as w ell as t o r ul e o ut excl usi o n ary 
di a g n os es.  T h e Scr e e n I nt er vi e w will ass ess t h e diff er e nt di a g n os es a n d d et er mi n e w hic h s u p pl e m e nts 
s h o ul d b e c o m pl et e d.  S u p pl e m e nt 4 ( N e ur o d e v el o p m e nt, Disr u ptiv e a n d C o n d uct Dis or d ers) m ust b e 
c o m pl et e d t o ass ess A D H D, O D D, C D Tic a n d A S D.  If a n excl usi o n ar y di a g n osis is c o nfir m e d, t h e 
r e m ai n d er of t h e di a g n ostic will n ot b e c o m pl et e d.  T his ass ess m e nt will b e a d mi nist er e d at Visit 1. 
5. 4. 8. 2  Si m ps o n- A n g us Sc al e 
T h e Si m ps o n- A n g us sc al e is a 1 0-it e m r ati n g sc al e t h at is wi d el y us e d f or ass ess m e nt of n e ur ol e ptic-
i n d uc e d P ar ki ns o nis m ( Si m ps o n 1 9 7 0).  It c o nsists of 1 it e m m e as uri n g g ait, 6 it e ms m e as uri n g ri gi dit y, 
a n d t hr e e it e ms m e as uri n g gl a b ell a t a p, tr e m or a n d s ali v ati o n, r es p ectiv ely.  T his ass ess m e nt will b e 
a d mi nist er e d at Visit 3 a n d all s u bs e q u e nt visits. 
5. 4. 8. 3  B ar n es A k at hisi a Sc al e 
T h e B ar n es A k at hisi a sc al e is a r ati n g sc al e f or dr u g-i n d uc e d a k at hisi a a n d i ncl u d es c o m p o n e nts f or 
r ati n g t h e o bs erv a bl e, r estl ess m ov e m e nts c h ar act eristic of a k at hisi a, t h e a w ar e n ess of r estl ess n ess, a n d 
a ny distr ess ass oci at e d wit h t h e c o n diti o n ( B ar n es 1 9 8 9).  T his ass ess m e nt will b e a d mi nist er e d at Visit 3 
a n d all s u bs e q u e nt visits. 
5. 4. 8. 4  A b n or m al I n v ol u nt ar y M o v e m e nt Sc al e ( AI M S) 
T h e AI M S t est is a r ati n g sc al e us e d t o m e as ur e t ar di v e dys ki n esi a ( M u n etz 1 9 8 8).  T h er e ar e 1 2 it e ms 
t h at r at e i nv ol u nt ar y m ov e m e nts of v ari o us ar e as of t h e s u bj ect’s b o dy.  T his ass ess m e nt will b e 
a d mi nist er e d at Visit 3 a n d all s u bs e q u e nt visits.  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
5. 4. 8. 5  Viti ell o A g gr essi o n Sc al e 
T h e Viti ell o A g gr essi o n Sc al e is a 1 0-it e m r ati n g sc al e t h at us es a cl ust er a n al ysis t o c at e g oriz e a g gr essi o n 
i nt o t w o s u bt y p es, pr e d at or y ( or pl a n n e d) a n d aff ectiv e ( or i m p ulsiv e) ( Viti ell o 1 9 9 0).  T his ass ess m e nt 
will b e a d mi nist er e d at Visit 1. 
5. 4. 8. 6  R etr os p ecti v e- M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S) 
T h e R etr os p ectiv e- M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S) w as d ev el o p e d t o g a u g e t h e s e v erit y of 
a g gr essi v e b e h avi or ( Bl a d er 2 0 1 0).   P ar e nts r at e t h e fr e q u e nc y ov er t h e p ast w e ek of 1 6 a g gr essiv e 
b e h a vi ors i n f o ur ar e as: v er b al a g gr essi o n; p hysic al a g gr essi o n t o w ar d ot h ers; a g gr essi o n t o w ar d 
o n es elf; a n d d estr ucti o n or h ostil e mis us e of pr o p erty.  N u m eric w ei g hti n g a m plifi es t h e s eri o us n ess of 
m or e h ar mf ul b e h avi ors i n t h e t ot al sc or e.  T his ass ess m e nt will b e a d mi nist er e d at Visit 1. 
5. 4. 8. 7  C ol u m bi a S uici d e S e v erit y R ati n g Sc al e ( C- S S R S) 
T h e C- S S R S is a q u esti o n n air e t h at pr os p ecti v el y ass ess es  s uici d al i d e ati o n a n d b e h a vi or usi n g a s e mi-
str uct ur e d i nt er vi e w t o pr o b e p ati e nt r es p o ns es ( P os n er 2 0 1 1).  T h e C- S S R S v ersi o ns a p plic a bl e t o t h e 
c urr e nt st u dy ar e t h e B as eli n e v ersi o n a n d t h e Si nc e L ast Visit v ersi o n. 
T h e B as eli n e v ersi o n of t h e sc al e ass ess es lif eti m e s uici d al i d e ati o n a n d b e h avi or.  T his v ersi o n is s uit a bl e 
as p art of a s u bj ect’s first i nt er vi e w a n d will b e us e d at Visit 1 t o i d e ntif y v ol u nt e ers w h o m ust n ot 
p artici p at e i n t h e tri al d u e t o t h eir s uici d al t e n d e nci es. 
T h e Si nc e L ast Visit v ersi o n of t h e sc al e ass ess es a n y s uici d al t h o u g hts or b e h a vi ors t h e s u bj ects m ay 
h a v e h a d si nc e t h e l ast a d mi nistr ati o n of t h e C- S S R S.  T his v ersi o n will b e us e d f or t h e ot h er st u dy visits. 
5. 4. 8. 8  I nfr e q u e nt B e h a vi ors C h ec klist 
T h e i nfr e q u e nt b e h avi ors c h ec klist is a c h ec klist of 1 5 b e h a vi ors t h at ( al o n g wit h t h e 1 5 I A Di ary 
b e h a vi ors) w er e q u alit ati v el y li n k e d t o I A d uri n g t h e d e v el o p m e nt of t h e I A di ary.  T h es e b e h avi ors 
i ncl u d e t e asi n g, s pitti n g, biti n g, w e a p o ns, ri p pi n g, br e a ki n g, v a n d alizi n g, d estr oyi n g, fir e s etti n g, hitti n g 
a ni m al, kic ki n g s elf, kicki n g a ni m al, s e v er e i nj ury s elf, s e v er e i nj ur y ot h ers, s e v er e i nj ur y a ni m al.  
C ar e gi v ers will b e ask e d w hic h, if a n y, of t h es e b e h avi ors h av e b e e n o bs erv e d si nc e t h e p ati e nt’s l ast 
visit.  T his ass ess m e nt will b e a d mi nist er e d at Visit 3, Visit 4, Visit 5, a n d Visit 6. 
6  S T A TI S TI C AL M E T H O D S 
6. 1  St atistic al a n d A n al ytic al Pl a ns 
T a b ul ar s u m m ari es of t h e d at a c oll ect e d d uri n g t h e st u dy will b e pr es e nt e d t o pr ovi d e a g e n er al 
d escri pti o n of t h e s u bj ects st u di e d a n d a n ov ervi e w of t h e Effic ac y, P K a n d s af ety r es ults.  D at a fr o m all 
sit es will b e c o m bi n e d i n t h e c o m p ut ati o n of t h es e s u m m ari es a n d s u m m ari es will b e pr es e nt e d b y 
tr e at m e nt gr o u p.  C o nti n u o us v ari a bl es will b e s u m m ariz e d usi n g d escri ptiv e st atistics ( n u m b er of 
s u bj ects, m e a n, st a n d ar d d e vi ati o n [ S D], m e di a n, a n d mi ni m u m a n d m axi m u m v al u es).  C at e g oric al 
( n o mi n al) v ari a bl es will b e s u m m ariz e d usi n g fr e q u e nc y t a bl es ( n u m b er a n d p erc e nt a g e of s u bj ects i n 
e ac h c at e g ory). 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
I n a d diti o n t o t a b ul ar s u m m ari es, s u bj ect d at a listi n gs, as s p ecifi e d i n S ecti o ns 1 6. 2 a n d 1 6. 4 of I C H 
G ui d a nc e E 3, will b e pr ovi d e d.  A d diti o n al s u bj ect d at a listi n gs t o b e pr ovi d e d f or t his st u dy ar e list e d 
u n d er t h e r el e v a nt s u bs ecti o ns b el o w. All d at a a n alys es will b e p erf or m e d b y t h e C R O aft er t h e st u dy is 
c o m pl et e d a n d t h e d at a b as e is r el e as e d.  St atistic al pr o gr a m mi n g a n d a n alys es will b e p erf or m e d usi n g 
S A S ® a n d/ or ot h er v ali d at e d st atistic al s oft w ar e as r e q uir e d. 
C o m pl et e d et ails of t h e st atistic al a n alysis will b e pr o vi d e d i n a s e p ar at e st atistic al a n al ysis pl a n ( S A P), 
w hic h will b e writt e n, fi n aliz e d, a n d a p pr o v e d pri or t o d at a b as e l oc k a n d will b e i ncl u d e d i n t h e Cli nic al 
St u dy R e p ort ( C S R) f or t his pr ot oc ol.  T h e st atistic al a n al ysis pl a n will s u p ers e d e t h e st atistic al a n alysis 
m et h o ds d escri b e d i n t his cli nic al pr ot oc ol . A ny d e vi ati o n fr o m t h e st atistic al pl a n will b e d oc u m e nt e d 
a n d d escri b e d i n t h e fi n al r e p ort.  If c h a n g es t o pri nci p al f e at ur es st at e d i n t h e pr ot oc ol ar e r e q uir e d, 
t h es e will b e d oc u m e nt e d i n a pr ot oc ol a m e n d m e nt.  T h e fi n al S A P will t a k e i nt o acc o u nt a ny 
a m e n d m e nt t o t h e pr ot oc ol. 
I n g e n er al, t h e b as eli n e v al u e f or a v ari a bl e is d efi n e d as t h e l ast o bs erv ati o n pri or t o t h e first d os e of 
d o u bl e- bli n d st u dy m e dic ati o n, i d e ally Visit 3, b ut i ncl u di n g t h e scr e e ni n g v al u e, if n ec ess ary. 
6. 2  H a n dli n g Missi n g D at a 
F or t h e pri m ary effic acy e n d p oi nt, t h e fr e q u e ncy of I A b e h a vi ors d uri n g t h e tr e at m e nt p eri o d will b e 
c alc ul at e d o v er t h e n u m b er of d ays wit h n o n- missi n g I A di ary d at a i n t h e tr e at m e nt p eri o d. N o ex plicit 
i m p ut ati o n of missi n g d at a will b e us e d, b ut t his a p pr o ac h is i m plicitl y e q ui v al e nt t o usi n g t h e fr e q u e ncy 
of I A b e h avi ors d uri n g t h e d a ys wit h n o n- missi n g I A di ar y d at a t o i m p ut e t h e fr e q u e nc y f or d a ys aft er 
st u dy disc o nti n u ati o n a n d d a ys wit h missi n g I A di ary d at a. 
6. 3  A n al ysis P o p ul ati o ns 
T h e p o p ul ati o n of “ a ll e nr oll e d s u bj ects” c o nsists of all t h os e scr e e n e d s u bj ects w h o m e et t h e 
r e q uir e m e nts f or st u dy p artici p ati o n a n d ar e e nt er e d i n t h e B as eli n e p eri o d of t h e st u dy.  T h e 
p o p ul ati o n of “ a ll r a n d o miz e d su bj ects” c o nsists of all t h os e e nr oll e d s u bj ects w h o c o m pl et e t h e 
B as eli n e P eri o d, m e et t h e i ncl usi o n/ excl usi o n crit eri a a n d ar e r a n d o miz e d. 
S af et y P o p ul ati o n:  will i ncl u d e all r a n d o miz e d s u bj ects w h o r ec ei v e d at l e ast 1 d os e of st u dy dr u g. 
I nt e nt-t o- Tr e at (I T T) P o p ul ati o n:  will i ncl u d e all s u bj ects w h o r ec eiv e d at l e ast 1 d os e of st u dy dr u g a n d 
h a v e a b as eli n e a n d at l e ast 1 v ali d p ost-r a n d o miz ati o n ass ess m e nt of fr e q u e ncy of I A b e h avi ors b as e d 
o n I A di ary e ntry. 
P er- Pr ot oc ol ( P P) P o p ul ati o n:  will i ncl u d e all of t h e s u bj ects i n t h e I T T p o p ul ati o n w h o c o m pl et e d t h e 
tr e at m e nt p eri o d wit h 8 0 % di ar y c o m pl eti o n c o m pli a nc e a n d w h o di d n ot h av e m aj or pr ot oc ol 
d e vi ati o ns. 
P K p o p ul ati o n:  will i ncl u d e all s u bj ects i n t h e s af et y p o p ul ati o n w h o h a d at l e ast o n e P K s a m pl e dr a w n 
w hic h h a d a q u a ntifi a bl e c o nc e ntr ati o n f or at l e ast o n e a n al yt e of i nt er est. 
T h e s af et y, I T T, P P , a n d P K p o p ul ati o ns ar e b as e d o n r a n d o miz e d tr e at m e nt r ec eiv e d. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
6. 4  D e m o gr a p hic a n d B as eli n e C h ar act eristics 
D e m o gr a p hic/ b as eli n e v ari a bl es i ncl u d e a g e, s ex, et h nicit y, r ac e, a n d h ei g ht at scr e e ni n g, w ei g ht at 
scr e e ni n g a n d b as eli n e, a n d m e dic al hist or y. T a b ul ar s u m m ari es of t h e d e m o gr a p hic/ b as eli n e v ari a bl es 
will b e pr es e nt e d f or t h e s af et y, I T T, a n d P P  p o p ul ati o ns, exc e pt f or m e dic al hist or y, w hic h will b e 
s u m m ariz e d f or t h e s af et y p o p ul ati o n o nl y. 
6. 5  S u bj ect Dis p ositi o n 
A dis p ositi o n of s u bj ects will i ncl u d e t h e n u m b er a n d p erc e nt a g e of s u bj ects i n e ac h of t h e f oll o wi n g 
c at e g ori es: 
 
S u bj ects i n t h e r a n d o miz e d p o p ul ati o n 
 
S u bj ects i n t h e I T T p o p ul ati o n 
 
S u bj ects tr e at e d (s af et y p o p ul ati o n) 
 
S u bj ects i n t h e P P st u dy p o p ul ati o n 
 
Wit hi n e ac h of t h e pr evi o us c at e g ori es, t h e n u m b er a n d p erc e nt a g e of s u bj ects w h o c o m pl et e d a n d 
disc o nti n u e d fr o m t h e st u dy will b e s u m m ariz e d. T h e r e as o ns f or st u dy disc o nti n u ati o n will als o b e 
s u m m ariz e d. T h e r e as o n f or disc o nti n u ati o n m a y i ncl u d e a ny of t h e f oll o wi n g:  
 
S u bj ect wit h dr e w c o ns e nt 
 
L ost t o f oll o w-u p  
 
A d mi nistr ativ e r e as o n 
 
A dv ers e ev e nt 
 
I nv esti g at or d ecisi o n 
 
F ail ur e t o f oll o w r e q uir e d st u dy pr oc e d ur es 
 
Ot h er 
O nly o n e ( pri m ar y) r e as o n f or st u dy disc o nti n u ati o n will b e r ec or d e d f or e ac h s u bj ect.  
6. 6   Pr ot oc ol D e vi ati o ns 
Pr ot oc ol d e vi ati o ns will b e pr es e nt e d i n listi n gs. If a p plic a bl e, t h e n u m b er a n d p erc e nt of s u bj ects wit hi n 
e ac h ty p e of pr ot oc ol d e vi ati o n will b e pr es e nt e d usi n g discr et e s u m m ary st atistics. Pr ot oc ol d evi ati o ns 
will i ncl u d e, b ut ar e n ot li mit e d t o: 
 
N o n-c o m pli a nc e wit h a ny sc h e d ul e d st u dy visit 
 
N o n-c o m pli a nc e wit h st u dy tr e at m e nt 
 
Dis all o w e d c o nc o mit a nt m e dic ati o ns 
 
N o n-c o m pli a nc e wit h st u dy i ncl usi o n or excl usi o n crit eri a 
 
N o n-c o m pli a nc e wit h st u dy ass ess m e nt pr oc e d ur es 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
6. 7  St u d y M e dic ati o n E x p os ur e a n d C o m pli a nc e 
D ur ati o n of ex p os ur e is d efi n e d as t h e t ot al n u m b er of d a ys a s u bj ect is ex p os e d t o a n y st u dy tr e at m e nt. 
T his will b e c alc ul at e d f or e ac h s u bj ect b y t a ki n g t h e diff er e nc e b et w e e n t h e d at e of l ast d os e mi n us t h e 
d at e of t h e first d os e, pl us 1 ( d at e of l ast d os e –  d at e of first d os e + 1).  
D ur ati o n of Tr e at m e nt ex p os ur e will als o b e s u m m ariz e d usi n g d escri pti v e st atistics ( n, m e a n, S D, 
m e di a n, mi ni m u m, a n d m axi m u m). 
P erc e nt of st u dy dr u g c o m pli a nc e is d efi n e d as {( n u m b er of t a bl ets dis p e ns e d – n u m b er of t a bl ets 
r et ur n e d) / 2 * ( d at e of l ast d os e – d at e of first d os e + 1)} * 1 0 0 %.  
F or e ac h tr e at m e nt, S M c o m pli a nc e will b e s u m m ariz e d b y c o m pli a nc e c at e g or y ( < 8 0 %, 8 0- 1 2 0 %, a n d 
> 1 2 0 %) a n d n u m b er of s u bj ects i n e ac h c o m pli a nc e c at e g ory.  St u dy m e dic ati o n c o m pli a nc e will als o b e 
s u m m ariz e d as a c o nti n u o us v ari a bl e usi n g d escri ptiv e st atistics ( n, m e a n, st a n d ar d d e vi ati o n, m e di a n, 
mi ni m u m, a n d m axi m u m) f or e ac h tr e at m e nt.    
S u m m ari es of tr e at m e nt c o m pli a nc e a n d ex p os ur e will b e pr es e nt e d s e p ar at ely f or t h e Titr ati o n P eri o d, 
M ai nt e n a nc e P eri o d, a n d c o m bi n e d Titr ati o n a n d M ai nt e n a nc e P eri o ds. 
6. 8  C o nc o mit a nt M e dic ati o ns 
C o nc o mit a nt m e dic ati o ns will b e assi g n e d a n 1 1- di git c o d e usi n g t h e W orl d H e alt h Or g a niz ati o n Dr u g 
Dicti o n ar y ( W H O D D) dr u g c o d es.  C o nc o mit a nt m e dic ati o ns will b e f urt h er c o d e d t o t h e a p pr o pri at e 
A n at o mic al- T h er a p e utic- C h e mic al ( A T C) c o d e i n dic ati n g t h er a p e utic cl assific ati o n.  A t a b ul ar s u m m ar y of 
c o nc o mit a nt m e dic ati o ns b y dr u g cl ass will b e pr es e nt e d f or t h e s af ety p o p ul ati o n. 
6. 9  Effic ac y A n al ys es 
6. 9. 1  
Pri m ar y Effic ac y A n al ysis 
T h e pri m ar y effic acy e n d p oi nt is t h e p erc e nt c h a n g e ( P C H T) i n t h e fr e q u e ncy ( u n w ei g ht e d sc or e) of I A 
b e h a vi ors p er 7 d ays i n t h e Tr e at m e nt ( Titr ati o n a n d M ai nt e n a nc e)  p eri o d r el ativ e t o t h e B as eli n e 
p eri o d c alc ul at e d o v er t h e n u m b er of d a ys wit h n o n- missi n g I A di ary d at a.   T h e fr e q u e nc y of I A 
b e h a vi ors p er 7 d ays is t h e s u m of sc or es f or all e v e nts i n a giv e n p eri o d of s e q u e nti al d a ys, a dj ust e d t o 7 
d a ys. 
T h e pri m ar y effic acy e n d p oi nt P C H T will b e c alc ul at e d by P C H T= 1 0 0 *( T –  B)/ B, w h er e T a n d B ar e I A 
b e h a vi or fr e q u e nci es p er 7 d a ys d uri n g t h e Tr e at m e nt p eri o d a n d b as eli n e p eri o d, r es p ecti v el y. T h e I A 
b e h a vi or fr e q u e ncy p er 7 d a ys is d efi n e d as ( S U M/ D A Y) x 7, w h er e S U M  is  t h e s u m of t h e I A b e h avi ors  
r e p ort e d i n t h e s u bj ect I A di ary, a n d D A Y is t h e n u m b er of d ays wit h n o n- missi n g I A fr e q u e nc y d at a i n 
t h e s u bj ect I A di ar y d uri n g t h e s p ecifi e d st u dy p eri o d. 
L et 1, 2, a n d 3 r e pr es e nt t h e m e di a n p erc e nt c h a n g e i n t h e fr e q u e ncy of I A b e h a vi ors p er 7 d a ys i n 
t h e Tr e at m e nt p eri o d r el ativ e t o t h e B as eli n e p eri o d i n t h e I T T p o p ul ati o n f or s u bj ects tr e at e d wit h 
Pl ac e b o, 1 8 m g a n d 3 6 m g d os es of S P N- 8 1 0, r es p ectiv el y.  T h e n ull ( H 0) a n d t h e alt er n ativ e ( Ha) 
hy p ot h es es ar e as i n t h e f oll o wi n g. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
H 0 1: 2= 1, (t h er e is n o diff er e nc e b et w e e n t h e m e di a n of t h e 1 8 m g d os e S P N- 8 1 0 a n d t h e 
m e di a n of pl ac e b o) vs. H
a 1: 2≠ 1,(t h er e is a diff er e nc e b et w e e n t h e m e di a n of t h e 1 8 m g d os e 
S P N- 8 1 0   a n d t h e m e di a n of pl ac e b o) 
 
H 0 2: 3= 1, (t h er e is n o diff er e nc e b et w e e n t h e m e di a n of t h e 3 6 m g d os e S P N- 8 1 0 a n d t h e 
m e di a n of pl ac e b o) vs. H
a 2: 3≠ 1,(t h er e is a diff er e nc e b et w e e n t h e m e di a n of t h e 3 6 m g d os e  
S P N- 8 1 0   a n d t h e m e di a n of pl ac e b o) 
T h e pri m ar y effic acy a n alysis will b e p erf or m e d usi n g t h e Wilc ox o n r a n k-s u m t est t o c o m p ar e t h e 
m e di a ns of e ac h of t h e t w o d os es of S P N- 8 1 0 ( 1 8 m g a n d 3 6 m g) wit h t h e m e di a n of t h e Pl ac e b o.  T h e 
H o d g es-L e h m a n n esti m at e a n d t h e ass oci at e d 9 5 % c o nfi d e nc e i nt erv al ( CI) will b e c alc ul at e d. T o 
pr es er v e t h e o v er all Ty p e I err or-r at e at 0. 0 5 0 f or t h e pri m ar y effic acy e n d p oi nt, m ulti plicity a dj ust m e nt 
d u e t o i nt eri m a n alysis a n d t w o c o m p aris o ns of S P N- 8 1 0 d os e gr o u p ( 1 8 m g a n d 3 6 m g) wit h t h e 
Pl ac e b o will b e p erf or m e d as d escri b e d i n S ecti o n 1 0. 1. 4 .  
6. 9. 2  
S ec o n d ar y Effic ac y A n al ys es 
T h e s ec o n d ary e n d p oi nts ar e: 
1.  Act u al C ar e giv er C GI-I sc or e at Visit 6   
2.  Act u al I nv esti g at or C GI-I sc or e at Visit 6 
3.  C h a n g e fr o m Visit 3 t o Visit 6 i n I nv esti g at or C GI- S sc or e 
4.  C h a n g e fr o m Visit 3 t o Visit 6 i n C H Q- 2 8 sc or e 
5.  C h a n g e fr o m Visit 3 t o Visit 6 i n P SI- 4- S F sc or es i n: 
a.  P ar e nt al Distr ess 
b.  P ar e nt- C hil d D ysf u ncti o n al I nt er acti o n 
c. Diffic ult C hil d 
6.  C h a n g e fr o m Visit 3 t o Visit 6 i n S N A P-I V A D H D sc or es i n: 
a.  I n att e nti o n r ati n gs 
b.  Hy p er activity/I m p ulsivity r ati n gs 
c. C o m bi n e d Sc al e r ati n gs  
E ac h o n e of t h e six s ec o n d ar y e n d p oi nts will b e a n alyz e d usi n g t h e a n al ysis of c ov ari a nc e m et h o d b as e d 
o n t h e I T T p o p ul ati o n wit h missi n g d at a i m p ut e d usi n g t h e L ast O bs erv ati o n C arri e d F or w ar d (L O C F) 
m et h o d. T h e m o d el i ncl u d es tr e at m e nt a n d b as eli n e as fix e d i n d e p e n d e nt c o v ari at es a n d c h a n g e fr o m 
b as eli n e t o fi n al m ai nt e n a nc e visit as a r es p o ns e v ari a bl e. T h e l e ast s q u ar es m e a n of e ac h tr e at m e nt 
gr o u p, t h e diff er e nc e i n t h e l e ast s q u ar es m e a n ( 1 8 m g d os e mi n us pl ac e b o a n d 3 6 m g d os e mi n us 
pl ac e b o), a n d t h e 2-si d e d 9 5 % CI f or t h e diff er e nc e will b e o bt ai n e d.   
T o pr es erv e t h e o v er all ty p e I err or r at e at 0. 0 5 f or t h e s ec o n d ar y e n d p oi nts, a s e q u e nti al t esti n g 
pr oc e d ur e will b e us e d wit h t h e f oll o wi n g f e at ur es. First o nly d os e or d os es t h at ar e si g nific a ntl y 
diff er e nt fr o m pl ac e b o f or t h e pri m ar y e n d p oi nt will b e t est e d f or s ec o n d ar y e n d p oi nts. T h e first of t h e 
s ec o n d ary e n d p oi nts will b e c o m p ar e d t o pl ac e b o usi n g t h e H oc h b er g st e p u p pr oc e d ur e b ut o nl y usi n g 
t h os e d os es r et ai n e d as a r es ult of t esti n g t h e pri m ary e n d p oi nt ( H oc h b er g 1 9 8 8). T h e s ec o n d s ec o n d ar y 
e n d p oi nt will b e t est e d i n t h e s a m e m a n n er b ut o nly usi n g t h os e d os es t h at w er e r et ai n e d fr o m t h e 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
pri m ar y a n d t h e first s ec o n d ar y e n d p oi nt a n d s o f ort h. As t h e e n d p oi nts ar e g o n e t hr o u g h i n t h e pr e-
d efi n e d or d er d os es will o nl y b e r et ai n e d if si g nific a nt f or all e n d p oi nts t est e d s o f ar a n d at t h e gi v e n 
st a g e t h e H oc h b er g st e p- u p pr oc e d ur e will b e a p pli e d. 
T h e or d eri n g of t h e  6 s ec o n d ar y e n d p oi nts fr o m first t o b e t est e d t o sixt h is: I nv esti g at or Cli nic al Gl o b al 
I m pr essi o n –  I m pr o v e m e nt Sc al e ( C GI-I)( E n d p oi nt 1), Cli nic al Gl o b al I m pr essi o n –  S e v erit y Sc al e ( C GI-S)  
( E n d p oi nt 2), C hil d H e alt h Q u esti o n n air e ( C H Q- 2 8) ( E n d p oi nt 3), P ar e nti n g Str ess I n d ex ( P SI- 4-S F ) 
( E n d p oi nt 4), C ar e giv er-c o m pl et e d C GI-I ( E n d p oi nt 5) a n d S N A P-I V R ati n g Sc al e ( E n d p oi nt 6).      
6. 9. 3  
S e nsiti vit y A n al ysis 
I n t h e pr es e nc e of a hi g h dr o p- o ut r at e, p erf or m a nc e of s e nsitivit y a n alysis is cr uci al.  T h e p ur p os e of 
s e nsiti vit y a n alysis is t o s e e w h et h er diff er e nt m et h o ds of h a n dli n g missi n g d at a pr o vi d e c o nsist e nt a n d 
si mil ar r es ults f or t h e pri m ar y effic ac y a n alysis.  T o t his e n d, t h e t hr e e s e nsiti vity a n al ys es will b e 
p erf or m e d: 
1.  M ulti pl e i m p ut ati o n u n d er M A R  usi n g av ail a bl e d at a o n t h e pri m ar y e n d p oi nt  
2.  Pl ac e b o-  b as e d i m p ut ati o n u n d er M N A R  
3.  P er Pr ot oc ol A n al ysis 
6. 9. 3. 1  M ulti pl e i m p ut ati o n u n d er Missi n g at R a n d o m ( M A R) 
T h e m ulti pl e i m p ut ati o n ( MI) m et h o d ass u m es t h at t h e missi n g d at a ar e missi n g at r a n d o m ( M A R), t h at 
is, t h e pr o b a bilit y t h at a n o bs er v ati o n is missi n g m ay d e p e n d o n t h e o bs erv e d v al u es b ut n ot t h e missi n g 
v al u es. F or ex a m pl e, if a s u bj ect’s Di ary v al u es ar e av ail a bl e o n D a y 1 a n d D ay 2 b ut missi n g o n D a y 3, 
t h e n t h e missi n g v al u e o n D a y 3 is r el at e d t o t h e n o n- missi n g  v al u e o n D a y 1 a n d D a y 2. 
MI is i m pl e m e nt e d usi n g t h e f oll o wi n g t hr e e st e ps.  
 
 
1)  S A S P R O C MI is a p pli e d wit h i n p ut d at as et c o nt ai ni n g s o m e missi n g v al u es f or all d a ys d uri n g t h e 
titr ati o n a n d m ai nt e n a nc e p eri o d t o cr e at e 1 0 0 d at as ets. T h e d at a s ets will i ncl u d e s e p ar at e 
c ol u m ns f or t h e fr e q u e ncy of i nci d e nc es d uri n g e ac h d a y st arti n g fr o m b as eli n e. T h e M ark ov 
C h ai n M o nt e C arl o ( M C M C) m et h o d will b e us e d t o c o m pl et e t h e missi n g n ess p att er n t o a 
m o n ot o n e p att er n s e p ar at el y b y tr e at m e nt ar m.  T h e m o n ot o n e p att er ns will b e ac hi e v e d b y 
a p pl yi n g s e q u e nti al i m p ut ati o n b as e d o n B a y esi a n r e gr essi o n wit h t h e tr e at m e nt ar m i ncl u d e d 
as a c o v ari at e.  All c o pi es c o nt ai n i d e ntic al v al u es of t h e n o n- missi n g d at a it e ms, b ut diff er e nt 
v al u es i m p ut e d f or missi n g v al u es.  
2)  F or e ac h of t h es e MI d at a s ets, t h e p erc e nt c h a n g e will b e c o m p ut e d as i n t h e o bs er v e d d at a s et 
a n d t h e pri m ar y a n alysis b as e d o n t h e Wilc ox o n r a n k-s u m t est will b e c o n d uct e d a n d as y m pt otic 
9 5 % c o nfi d e nc e i nt erv als will b e c o nstr uct e d. 
3)  T o pr o d uc e a si n gl e c o nfi d e nc e i nt erv al f or e ac h d os e pl ac e b o c o m p aris o n ( e. g., D os e 1 v ers us 
pl ac e b o), P R O C MI A N AL Y Z E will b e us e d a n d R u bi n’s c o m bi n ati o n r ul es will b e a p pli e d t o t h e 
tr e at m e nt eff ect esti m at es a n d ass oci at e d asy m pt otic st a n d ar d err ors fr o m t h e MI d at a s ets.  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T h e tr e at m e nt eff ect esti m at es will b e d efi n e d as t h e mi d p oi nts of t h e as y m pt otic c o nfi d e nc e 
i nt er v als a n d t h e st a n d ar d err ors will b e d efi n e d as t h e as y m pt otic st a n d ar d err ors ( b as e d o n 
t h e wi dt h of t h e ass oci at e d 9 5 % c o nfi d e nc e i nt erv als) fr o m t h e H o d g es-L e h m a n n esti m at e of 
t h e i n di vi d u al d at as ets ( R u bi n 1 9 8 7). 
6. 9. 3. 2  M ulti pl e i m p ut ati o n u n d er Missi n g N ot at R a n d o m ( M N A R) 
T his a p pr o ac h c a n b e l a b el e d “ w orst -c as e” s e nsitivity a n al ys es as it ass u m es t h at aft er disc o nti n u ati o n 
s u bj ects fr o m t h e d osi n g ar ms w o ul d a d o pt t h e o utc o m e m o d el esti m at e d fr o m t h e pl ac e b o ar m.  T o 
g e n er at e missi n g v al u es fr o m t his “ pl ac e b o -b as e d” i m p ut ati o n m o d el, P R O C MI wit h t h e M N A R 
st at e m e nt ( av ail a bl e i n S A S 9. 3 a n d l at er v ersi o ns) will b e us e d or, alt er n ativ el y, S A S m acr os av ail a bl e at 
t h e DI A Missi n g D at a W or ki n g Gr o u p sit e ( R atitc h et al., 2 0 1 3; Ay el e et al., 2 0 1 4) c a n b e us e d. 
6. 9. 3. 3  P er Pr ot oc ol A n al ysis 
T his a n al ysis will b e c o n d uct e d b y r e p e ati n g t h e pri m ar y a n al ysis o n t h e p er pr ot oc ol p o p ul ati o n. 
6. 1 0  S a m pl e Siz e a n d P o w er C o nsi d er ati o ns 
B as e d o n r es ults fr o m t h e P h as e 2 st u dy, it is ass u m e d t h at t h e a v er a g e tr e at m e nt diff er e nc e b et w e e n 
S P N- 8 1 0 d os e gr o u ps a n d pl ac e b o is 1 1. 5 1 wit h a c o m m o n st a n d ar d d evi ati o n of 2 7. 3. A s a m pl e siz e of 
1 3 2 s u bj ects p er ar m ( 2 6 4  s u bj ects f or 3 ar ms) will yi el d 9 0 % p o w er t o d et ect a n o n-z er o diff er e nc e 
b et w e e n t h e m e di a n of 1 8 m g or 3 6 m g d os e gr o u p a n d t h e pl ac e b o usi n g t h e Wilc ox o n r a n k-s u m t est 
wit h a 2-si d e d si g nific a nc e l e v el al p h a = 0. 0 5.  
It is ass u m e d t h at a p pr oxi m at el y 2 0 % of  s u bj ects will dr o p o ut b ef or e t h e c o m pl eti o n of t h e st u dy a n d 
h e nc e, a n a dj ust e d t ot al of 3 3 0  s u bj ects will b e r a n d o miz e d i n a 1: 1: 1 r ati o t o o bt ai n 2 6 4 s u bj ects i n t h e 
I T T p o p ul ati o n at t h e c o m pl eti o n of t h e st u dy.   
T h e s a m pl e siz e w as c alc ul at e d usi n g t h e n Q u er y A dvis or S oft w ar e, V ersi o n 7.    
6. 1 1  I nt eri m A n al ysis 
T h e m ai n p ur p os e of t h e i nt eri m a n al ysis is t o r e- esti m at e t h e s a m pl e siz e. T h e s a m pl e siz e esti m at e 
d escri b e d i n t h e s a m pl e siz e S ecti o n  6. 1 0  is b as e d o n eff ect siz e ass u m pti o ns fr o m t h e P h as e 2 d at a i n 
w hic h t h e pri m ary e n d p oi nt w as t h e c h a n g e fr o m b as eli n e t o e n d p oi nt i n R- M O AS r ati n gs. H o w e v er, t h e 
pri m ar y e n d p oi nt f or t his st u dy is p erc e nt c h a n g e i n t h e fr e q u e ncy  of I A i nci d e nc e p er 7 d ays i n t h e 
Tr e at m e nt ( Titr ati o n a n d M ai nt e n a nc e) p eri o d ( P C H T) r el ativ e t o t h e B as eli n e p eri o d i n t h e I T T 
p o p ul ati o n c alc ul at e d ov er t h e n u m b er of d a ys wit h n o n- missi n g I A di ar y d at a. H e nc e, t h er e is 
u nc ert ai nt y as t o w h at m a g nit u d e of alt er n ativ e h y p ot h esis tr e at m e nt diff er e nc e a n d b et w e e n-s u bj ect 
v ari a bilit y is a p pr o pri at e t o pr e-s p ecify. T o t his e n d, a si n gl e i nt eri m a n alysis is pl a n n e d aft er 
a p pr oxi m at ely 5 0 % of s u bj ects c o m pl et e t h e st u dy. T h e a d a pti v e d esi g n pl a n f or t h e i nt eri m a n alysis 
pl a n is pr es e nt e d i n t h e A p p e n dix 1 0. 1 . 
6. 1 2  Ass ess m e nt of M CI C 
B as e d o n u n bli n d e d d at a av ail a bl e at st u dy cl os e, t h e a bilit y of a p erc e nt c h a n g e ( P C H) e n d p oi nt t o 
d et ect c h a n g e will b e e v al u at e d usi n g t hr e e a nc h or- b as e d mi ni m al cli nic ally i m p ort a nt c h a n g e ( M CI C) 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 6 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
esti m at es o bt ai n e d fr o m t w o gl o b al i m pr essi o n of c h a n g e ( C GI-I) v ari a bl es a n d o n e gl o b al i m pr essi o n of 
s e v erit y ( C GI- S) v ari a bl e. C o nsist e nt wit h t h e r ec o m m e n d ati o ns of H ays ( H ays et al., 2 0 0 5), t h e 
ass ess m e nt of d et ecti o n of cli nic all y m e a ni n gf ul c h a n g e will e m p h asiz e u nst a n d ar diz e d a nc h or- b as e d 
esti m at es “ s o t h at us ers of t h e m e as ur e will b e a bl e t o i nt er pr et diff er e nc es i n t h e r a w m etric.” 
T h e a nc h or- b as e d M CI C v al u es will b e o bt ai n e d b y esti m ati n g t h e av er a g e P C H f or mi ni m al 
i m pr ov e m e nt gr o u ps d efi n e d b y r ati n gs fr o m t w o r at ers f or t w o c o nc e pts. I n v esti g at ors a n d c ar e giv ers 
will e ac h r at e gl o b al i m pr essi o n of c h a n g e.  T h es e will b e k n o w n as I nv esti g at or-r at e d C GI-I a n d 
C ar e gi v er-r at e d C GI-I, r es p ecti v el y.  H o w ev er, o nly i n v esti g at ors will r at e gl o b al i m pr essi o n of s e v erit y 
( C GI- S). T h es e C GI-I/ C GI- S m e as ur es will b e o bt ai n e d at m ulti pl e sit e visits ( Visit 3, Visit 4, Visit 5, a n d 
Visit 6) t hr o u g h o ut t h e st u dy p eri o d t o r e d uc e r ec all err or a n d q u a ntif y i ncr e m e nt al c h a n g e o v er ti m e . 
I nv esti g at or-r at e d C GI-I a n d C ar e gi v er-r at e d C GI-I will b e ass ess e d o n a 7- p oi nt sc al e wit h 1 = V er y m uc h 
i m pr ov e d, 2 = M uc h i m pr ov e d, 3 = Mi ni m ally i m pr o v e d, 4 = N o c h a n g e, 5 = Mi ni m ally w ors e, 6 = M uc h w ors e, 
a n d 7 = V ery m uc h w ors e. C GI S will b e e v al u at e d o n a 7- p oi nt sc al e wit h 1 = N or m al, 2 = B or d erli n e ill, 
3 = Mil dly ill, 4 = M o d er at ely ill, 5 = M ar k e dl y ill, 6 = S e v er ely ill, a n d 7 = Extr e m ely ill. Mi ni m al i m pr ov e m e nt 
gr o u ps (r ati n g of 3) f or a fix e d ass ess m e nt c o ntr ast ( e. g. Visit 3 vs. Vis it 4, Visit 3 vs. Visit 5, a n d Visit 3 vs. 
Visit 6) d efi n e t h e M CI C a nc h or o n I nv esti g at or-r at e d C GI-I a n d C ar e gi v er-r at e d C GI-I. T o d efi n e a n M CI C 
a nc h or o n C GI- S, t h e diff er e nc e i n s e v erity r ati n gs acr oss ass ess m e nt i nt erv al ( e. g. Visit 4 mi n us Visit 3, 
Visit 5 mi n us Visit 3, a n d Visit 6 mi n us Visit 3) will b e c alc ul at e d wit h t h os e ex hi biti n g mi ni m al 
i m pr ov e m e nt i n s ev erit y acr oss i nt er v als us e d t o d efi n e t h e M CI C a nc h or. Mi ni m al i m pr ov e m e nt o n C GI-
S is c alc ul at e d as a o n e c at e g or y c h a n g e of i m pr ov e m e nt, e. g. c h a n gi n g fr o m a v al u e of mil dl y ill at 
b as eli n e t o b or d erli n e ill at titr ati o n or m ar k e dly ill at b as eli n e t o m o d er at el y ill at m ai nt e n a nc e. 
T o c alc ul at e M CI C f or e ac h of t h e C GI-I/ C GI- S a nc h ors d efi n e d a b ov e, P C H sc or es will b e c alc ul at e d by 
visit: Visit 4, Visit 5, a n d Visit 6. Wit h t hr e e visits at w hic h M CI C will b e c alc ul at e d, t h e t hr e e P C H 
v ari a bl es m ay b e ex pr ess e d as P C H 3, 4= 1 0 0 ∗(
V 4 −B
B
) , P C H3, 5= 1 0 0 ∗(
V 5 −B
B
) , a n d P C H3, 6= 1 0 0 ∗(
V 6 −B
B
) , 
w h er e V 4- B, V 5- B, a n d V 6- B ar e t h e diff er e nc e i n u n w ei g ht e d sc or es a dj ust e d t o 7 d a ys b et w e e n Visit 4 
a n d b as eli n e, Visit 5 a n d b as eli n e, a n d Visit 6 a n d b as eli n e, r es p ecti v el y. T h e M CI C v al u es will b e 
o bt ai n e d fr o m a n A N O V A esti m at e d usi n g S A S’ GL M pr oc e d ur e wit h P C H as o utc o m e a n d t h e a nc h ors: 
I nv esti g at or-r at e d C GI-I, C ar e giv er-r at e d C GI-I, a n d c h a n g e i n C GI- S sc or es as fix e d i n d e p e n d e nt 
cl assific ati o n v ari a bl es. Wit h t hr e e ass ess m e nt occ asi o ns ( Visit 4, Visit 5 a n d Visit 6) f or w hic h P C H will 
b e c alc ul at e d a n d t hr e e a nc h ors (I nv esti g at or-r at e d C GI-I, C ar e gi v er-r at e d C GI-I, a n d C GI- S )  at e ac h 
occ asi o n t h er e will b e a t ot al of 9 P C H a n d a nc h or c o m bi n ati o ns.  A S e p ar at e o n e- w a y A N O V A will b e fit 
f or e ac h of t h e 9 P C H a n d a nc h or c o m bi n ati o ns.  Wit hi n a gi v e n P C H a n d a nc h or c o m bi n ati o n, t h e 
a v er a g e P C H v al u e f or e ac h l e v el of t h e a nc h or will b e esti m at e d, wit h t h e M CI C esti m at e c orr es p o n di n g 
t o t h e av er a g e P C H v al u e f or t h e mi ni m al i m pr o v e m e nt gr o u p.  C o nsist e nt wit h c urr e nt b est pr actic e f or 
M CI C r e p orti n g, ( H a ys et al., 2 0 0 5) t h e A N O V A esti m at e d 9 5 % c o nfi d e nc e i nt er v al f or t h e M CI C 
esti m at es will als o b e pr o vi d e d. M CI C esti m at es will b e tri a n g ul at e d i n a n att e m pt t o est a blis h t h e a bilit y 
of t h e I A di ary sc or e t o d et ect cli nic ally m e a ni n gf ul c h a n g e.  
I n a d diti o n, t h e c u m ul ati v e distri b uti o n f u ncti o ns ( C D Fs) f or P C H fr o m b as eli n e t o e ac h visit will b e 
ex pl or e d gr a p hic all y.  T h e C D Fs f or e ac h a nc h or c at e g or y str at u m will b e pl ott e d f or e ac h ass ess m e nt 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
c o m bi n ati o n ( visit 3 vs. 4, visit 3 vs. 5, a n d visit 3 vs. 6), a n d wit hi n e ac h ass ess m e nt c o m bi n ati o n t hr e e 
a nc h or-s p ecific C D F pl ots will b e g e n er at e d.  Gi v e n t h at t h e C GI-I a n d C GI- S e ac h h a v e s e v e n c at e g ori es, 
C D Fs f or t h e C GI-I a n d C GI-S m e as ur es will dis pl a y s ev e n t ot al C D Fs.  Giv e n t h at t h e C GI- S h as s e v e n 
c at e g ori es b ut t h e a nc h or will b e c o nv ert e d t o o n e-c at e g ory c h a n g e v al u es f or M CI C esti m ati o n, a n 
a d diti o n al C GI- S pl ot will b e pr o d uc e d dis pl a yi n g six C D Fs, o n e f or e ac h o n e-c at e g or y c h a n g e v al u e ( 1 t o 
2, 2 t o 3, . . ., 6 t o 7) at e ac h ass ess m e nt c o m bi n ati o n i n or d er t o ass ess t h e u nif or mity of P C H acr oss 
e ac h p ossi bl e o n e- p oi nt c h a n g e c o m bi n ati o n.  I n a d diti o n, t h e C D Fs f or e ac h tr e at m e nt ar m will b e 
pl ott e d.  T o a u g m e nt t h e i nt er pr et ati o n of t h e I A di ary’s a bilit y t o d et ect m e a ni n gf ul c h a n g e, t h e M CI C 
esti m at es will b e d e m arc at e d i n t h e tr e at m e nt-str atifi e d C D F pl ots a n d t h e tr e at m e nt- ar m s p ecific 
pr o p orti o ns ac hi e vi n g t h e M CI C esti m at es will b e r e p ort e d a n d c o m p ar e d. 
6. 1 3  P h ar m ac o ki n etic A n al ys es 
 
 
 
 
 
 
 
 
 
   
 
 
 
6. 1 4  S af et y A n al ys es 
E v al u ati o n of s af et y will b e p erf or m e d f or t h e s af et y p o p ul ati o n.  S af ety d at a t h at will b e e v al u at e d 
i ncl u d e c o nc o mit a nt m e dic ati o ns, A Es, cli nic al l a b or at or y r es ults, vit al si g ns, E C Gs, a n d fi n di n gs fr o m t h e 
p hysic al ex a mi n ati o ns.  T h e occ urr e nc e of n e ur ol o gic al si d e eff ects will b e ass ess e d b y l o o ki n g at a ny 
w ors e ni n g i n sc or es fr o m Visit 3 t o e ac h s u bs e q u e nt visit f or e ac h of t h e Si m ps o n- A n g us sc al e, B ar n es 
A k at hisi a sc al e, a n d AI M S. S uici d al i d e ati o n a n d s uici d al b e h a vi or will b e m e as ur e d b y C- S S R S. 
All s u m m ar y t a bl es r el at e d t o s af ety a n alys es will us e t h e s af ety p o p ul ati o n. 
6. 1 4. 1  A d v ers e E v e nts 
A Es will b e cl assifi e d i nt o st a n d ar diz e d m e dic al t er mi n ol o gy fr o m t h e v er b ati m d escri pti o n (I nv esti g at or 
t er m) usi n g t h e M e dic al Dicti o n ary f or R e g ul at ory Activiti es ( M e d D R A).  A Es will b e s u m m ariz e d usi n g 
discr et e s u m m ari es at t h e s u bj ect a n d ev e nt l ev el by s yst e m or g a n cl ass a n d pr ef err e d t er m f or e ac h 
tr e at m e nt gr o u p.  Si mil arly, tr e at m e nt- e m er g e nt A Es will b e s u m m ariz e d b y s ev erit y a n d r el ati o ns hi p 
s e p ar at ely.  V er b ati m d escri pti o n a n d all M e d D R A l ev el t er ms, i ncl u di n g t h e l o w er l e v el t er ms, f or all A Es 
will b e c o nt ai n e d i n t h e s u bj ect d at a listi n gs. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
All A Es occ urri n g aft er r a n d o miz ati o n a n d t hr o u g h o ut t h e st u dy p eri o d will b e r ec or d e d.  F or s u bj ects 
w h o r ec eiv e S M, tr e at m e nt- e m er g e nt A Es ( T E A Es) will b e c oll ect e d st arti n g aft er t h e first d os e of S M 
( Visit 3) t o t h e e n d of t h e st u dy.  T h es e A Es i ncl u d e t h os e t h at e m er g e d uri n g tr e at m e nt or w ors e n i n 
s e v erit y d uri n g tr e at m e nt. T h es e A Es will b e t a b ul at e d, list e d a n d a n alyz e d. 
S e p ar at e T E A E i nci d e nc e t a bl es will b e pr es e nt e d f or t h e t hr e e tr e at m e nt gr o u ps.  T h e i nci d e nc e r at es 
f or all S A D Rs will als o b e s u m m ariz e d as d escri b e d f or all T E A Es. 
I n a d diti o n, t h es e s a m e t a bl es will b e pr es e nt e d by tr e at m e nt p eri o d ( Titr ati o n, M ai nt e n a nc e, a n d 
c o m bi n e d Titr ati o n a n d M ai nt e n a nc e).  F or t h e c o m bi n e d Titr ati o n a n d M ai nt e n a nc e P eri o ds, t h e 
i nci d e nc e of T E A Es will als o b e pr es e nt e d by hi g h est s ev erity r e p ort e d a n d t h e d os e of S M at first 
occ urr e nc e.   
Listi n gs ( a n d t a b ul ar s u m m ari es, if w arr a nt e d) of d e at hs, ot h er S A Es, a n d ot h er si g nific a nt T E A Es, 
i ncl u di n g T E A Es r es ulti n g i n tr e at m e nt disc o nti n u ati o n, will b e pr ovi d e d. 
6. 1 4. 2  L a b or at or y V al u es 
Cli nic al l a b or at ory v al u es will b e s u m m ariz e d b y visit by tr e at m e nt gr o u p usi n g d escri pti v e st atistics f or 
h e m at ol o gy a n d bi oc h e mistr y.  F or q u a ntit ati v e l a b or at or y p ar a m et ers, b ot h act u al v al u es a n d c h a n g e 
fr o m b as eli n e v al u es will b e s u m m ariz e d.   
L a b or at ory t est r es ults will b e assi g n e d a l o w, n or m al, hi g h (L N H) cl assific ati o n acc or di n g t o w h et h er t h e 
v al u es w er e b el o w (L), wit hi n ( N), or a b ov e ( H) t h e l a b or at or y p ar a m et ers’ r ef er e nc e r a n g es p r o vi d e d b y 
t h e c e ntr al l a b or at or y.  Wit hi n-tr e at m e nt c o m p aris o ns will b e b as e d o n t hr e e by t hr e e t a bl es (s hift 
t a bl es) t h at, f or a p artic ul ar l a b or at or y t est, c o m p ar e t h e L N H cl assific ati o n at b as eli n e t o t h e L N H 
cl assific ati o n at visit.  By s u bj ect-listi n gs of all a b n or m al l a b or at or y v al u es, i. e., t h os e wit h L or H 
cl assific ati o n will b e pr o vi d e d. 
6. 1 4. 3  Vit al Si g ns, H ei g ht a n d W ei g ht 
Vit al si g ns will b e s u m m ariz e d b y visit by tr e at m e nt gr o u p usi n g d escri ptiv e st atistics.  B ot h act u al v al u es 
c h a n g es fr o m b as eli n e t o visit will b e s u m m ariz e d.  D escri pti v e s u m m ary st atistics ( m e a n, S D, m e di a n, 
a n d r a n g e) f or vit al si g n d at a, h ei g ht, w ei g ht a n d B MI will b e e v al u at e d b y tr e at m e nt gr o u p. 
6. 1 4. 4  E C G R es ults 
B y -visit t a b ul ar s u m m ari es of t h e q u a ntit ativ e E C G p ar a m et ers a n d t h e o v er all E C G fi n di n gs ( n or m al, 
a b n or m al n ot cli nic all y si g nific a nt, or a b n or m al cli nic all y si g nific a nt) will b e pr es e nt e d.   T h e Q T will b e 
c orr ect e d usi n g Fri d erici a’s m et h o d. 
E C G r es ults will b e s u m m ariz e d b y visit b y tr e at m e nt gr o u p usi n g d escri ptiv e st atistics (f or q u a ntit ati v e 
E C G p ar a m et ers) a n d fr e q u e nc y t a bl es (f or q u alit ati v e E C G p ar a m et ers, i ncl u di n g t h e o v er all E C G 
fi n di n g).  F or q u a ntit ativ e E C G p ar a m et ers, b ot h act u al v al u es a n d c h a n g e fr o m scr e e ni n g v al u es will b e 
s u m m ariz e d.   

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
6. 1 4. 5  P h ysic al E x a mi n ati o ns 
Fi n di n gs fr o m t h e p hysic al ex a mi n ati o ns will b e list e d f or e ac h s yst e m or ar e a ex a mi n e d. 
6. 1 4. 6  C ol u m bi a S uici d e S e v erit y R ati n g Sc al e ( C- S S R S) 
C- S S R S o utc o m es will b e s u m m ariz e d usi n g n u m b er a n d p erc e nt of s u bj ects b y c at e g ori es f or s uici d al 
i d e ati o n o nl y, s uici d al b e h avi or o nl y a n d s uici d ality (i d e ati o n a n d b e h avi or c o m bi n e d). T h e s u m m ar y will 
b e pr es e nt e d by tr e at m e nt gr o u ps.  T h e pr o p orti o n of s u bj ects i n e ac h tr e at m e nt gr o u p will b e 
c o m p ar e d wit h t h e pr o p orti o n of s u bj ects i n t h e pl ac e b o gr o u p usi n g Fis h er’s ex act t est or C hi -s q u ar e 
t est as a p plic a bl e if a p pr o pri at e.  
6. 1 4. 7  I nfr e q u e nt B e h a vi ors C h ec klist 
I nfr e q u e nt b e h a vi ors will b e list e d f or e ac h s u bj ect by tr e at m e nt gr o u p. 
6. 1 4. 8  Ot h er S p eci al T ests 
T h e occ urr e nc e of n e ur ol o gic al si d e eff ects will b e ass ess e d by l o o ki n g at t h e c h a n g es i n sc or es fr o m 
b as eli n e t o p ost- b as eli n e visits f or e ac h of t h e Si m ps o n- A n g us sc al e, B ar n es A k at hisi a sc al e, a n d AI M S.  
F or e ac h it e m o n e ac h of t h es e sc al es, t h e n u m b er ( a n d p erc e nt a g e) of s u bj ects wit h a w ors e sc or e at 
a ny p ost- b as eli n e visit, c o m p ar e d t o b as eli n e, will b e pr es e nt e d.  A listi n g of t h es e s u bj ects will als o b e 
pr o vi d e d.  
7  D O C U M E N T A TI O N 
7. 1  A d h er e nc e t o t h e Pr ot oc ol 
T h e I nv esti g at or a gr e es, w h e n si g ni n g t h e pr ot oc ol, t o a d h er e t o t h e i nstr ucti o ns a n d pr oc e d ur es 
d escri b e d i n t h e pr ot oc ol a n d t o a d h er e t o t h e pri nci pl es of I C H G C P t o w hic h t h e pr ot oc ol c o nf or ms as 
w ell as all g ov er ni n g l oc al r e g ul ati o ns a n d pri nci pl es f or m e dic al r es e arc h. 
T h e pr ot oc ol, I C F, a n d a p pr o pri at e r el at e d d oc u m e nts m ust b e r evi e w e d a n d a p pr o v e d b y a n I R B 
c o nstit ut e d a n d f u ncti o ni n g i n acc or d a nc e wit h I C H E 6 a n d a n y l oc al r e g ul ati o ns. D oc u m e nt ati o n of I R B 
c o m pli a nc e wit h t h e I C H a n d a n y l oc al r e g ul ati o ns r e g ar di n g c o nstit uti o n a n d r e vi e w c o n d uct will b e 
pr o vi d e d t o t h e S p o ns or. 
A si g n e d l ett er of st u dy a p pr o v al fr o m t h e I R B C h air m a n m ust b e s e nt t o t h e I nv esti g at or wit h a c o py t o 
t h e S p o ns or pri or t o st u dy st art a n d t h e r el e as e of a n y S M t o t h e sit e by t h e S p o ns or or its d esi g n e e.  If 
t h e I R B d eci d es t o s us p e n d or t er mi n at e t h e st u dy, t h e I nv esti g at or will i m m e di at el y s e n d t h e n otic e of 
st u dy s us p e nsi o n or t er mi n ati o n b y t h e I R B t o t h e S p o ns or. 
St u dy pr o gr ess is t o b e r e p ort e d t o I R B a n n u ally ( or as r e q uir e d) by t h e I nv esti g at or or S p o ns or, 
d e p e n di n g o n l oc al r e g ul at or y o bli g ati o ns.  If t h e I n v esti g at or is r e q uir e d t o r e p ort t o t h e I R B, h e/s h e will 
f or w ar d a c o py t o t h e S p o ns or at t h e ti m e of e ac h p eri o dic r e p ort.   
7. 2  C h a n g es t o t h e Pr ot oc ol 
T h er e ar e t o b e n o c h a n g es t o t h e pr ot oc ol wit h o ut writt e n a p pr ov al fr o m t h e S p o ns or.   

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
A ny c h a n g e t o t h e pr ot oc ol r e q uir es a writt e n pr ot oc ol a m e n d m e nt or a d mi nistr ati v e c h a n g e t h at m ust 
b e a p pr ov e d b y t h e S p o ns or b ef or e i m pl e m e nt ati o n.  A m e n d m e nts s p ecific ally aff ecti n g t h e s af et y of 
s u bj ects, t h e sc o p e of t h e i nv esti g ati o n, or t h e sci e ntific q u alit y of t h e st u dy r e q uir e a d diti o n al a p pr ov al 
by t h e a p plic a bl e I R Bs a n d, i n s o m e c o u ntri es, by t h e r e g ul at ory a ut h orit y.  T h es e r e q uir e m e nts s h o ul d 
i n n o w ay pr ev e nt a ny i m m e di at e acti o n fr o m b ei n g t ak e n b y t h e I nv esti g at or, or by t h e S p o ns or, i n t he 
i nt er est of pr es ervi n g t h e s af et y of all s u bj ects i ncl u d e d i n t h e st u dy.  If a n i m m e di at e c h a n g e t o t h e 
pr ot oc ol is w arr a nt e d as p er t h e I n v esti g at or, f or s af ety r e as o ns, t h e M e dic al M o nit or a n d I R B m ust b e 
n otifi e d pr o m ptl y. 
C h a n g es aff ecti n g o nl y a d mi nistr ativ e as p ects of t h e st u dy d o n ot r e q uir e f or m al pr ot oc ol a m e n d m e nts 
or I R B a p pr ov al, b ut t h e I R B m ust b e k e pt i nf or m e d of s uc h c h a n g es.  I n t h es e c as es, t h e S p o ns or will 
s e n d a l ett er t o t h e I R B d et aili n g s uc h c h a n g es. 
7. 3  Pr ot oc ol D e vi ati o ns 
T h er e ar e t o b e n o I nv esti g at or-i niti at e d d evi ati o ns fr o m t h e pr ot oc ol.  A ny s u bj ect w h os e tr e at m e nt 
d e vi at es fr o m t h e pr ot oc ol or w h o is n ot q u alifi e d f or st u dy p artici p ati o n m a y b e i n eli gi bl e f or a n alysis 
a n d m a y c o m pr o mis e t h e st u dy.  T h e d at e of a n d r e as o n f or d evi ati o ns m ust b e d oc u m e nt e d i n all c as es. 
Si g nific a nt or m aj or pr ot oc ol d evi ati o ns i m p acti n g t h e s af ety of t h e s u bj ect or t h e i nt e grity of t h e st u dy 
m ust b e r e p ort e d b y t h e I nv esti g at or t o t h e I R B i m m e di at el y. R e p orti n g of all ot h er pr ot oc ol d e vi ati o ns 
m ust a d h er e t o t h e r e q uir e m e nts of t h e g ov er ni n g I R B. Pr ot oc ol ass ess m e nts will c o nti n u e u ntil t h e e n d 
of t h e st u dy, u nl ess t h e pr ot oc ol d evi ati o ns p ut t h e s u bj ect at ris k or t h e s u bj ect’s c o n diti o n r e q uir es 
t h at h e/s h e b e disc o nti n u e d fr o m t h e st u dy. 
7. 4  D at a Q u alit y Ass ur a nc e 
T his st u dy will b e or g a niz e d, p erf or m e d, a n d r e p ort e d i n c o m pli a nc e wit h t h e pr ot oc ol, st a n d ar d 
o p er ati n g pr oc e d ur es ( S O Ps), w or ki n g pr actic e d oc u m e nts, a n d a p plic a bl e r e g ul ati o ns a n d g ui d eli n es.  
Sit e visit a u dits m ay b e m a d e p eri o dic ally b y t h e S p o ns or’s Q u alit y Ass ur a nc e t e a m or q u alifi e d 
d esi g n e e, w hic h is a n i n d e p e n d e nt f u ncti o n fr o m t h e st u dy c o n d uct t e a m. 
7. 4. 1  
D at a C oll ecti o n 
T h e pri m ar y s o urc e d oc u m e nt will b e t h e s u bj ect’s m e dic al r ec or d.  If s e p ar at e r es e arc h r ec or ds ar e 
m ai nt ai n e d by t h e I nv esti g at or(s), b ot h t h e m e dic al r ec or d a n d t h e r es e arc h r ec or d will b e c o nsi d er e d 
t h e s o urc e d oc u m e nts f or t h e p ur p os es of m o nit ori n g a n d a u diti n g t h e st u dy. 
El ectr o nic d at a c oll ecti o n t ec h ni q u es will b e us e d t o c oll ect d at a dir ectly fr o m t h e st u dy sit es usi n g 
e C R Fs.  T h e el ectr o nic d at a will b e st or e d c e ntr ally i n a f ull y v ali d at e d cli nic al d at a b as e. 
 
 
 
/ pr o gr a ms. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
D at a r ec or d e d o n s o urc e d oc u m e nts will b e tr a nscri b e d i nt o t h e e C R Fs i n acc or d a nc e wit h t h e e C R F 
C o m pl eti o n I nstr ucti o ns t h at ar e pr ovi d e d t o t h e st u dy sit es.  T h e I nv esti g at or is r es p o nsi bl e f or e ns uri n g 
t h at all s ecti o ns of e ac h e C R F ar e c o m pl et e d c orr ectl y, a n d t h at e ntri es c a n b e v erifi e d a g ai nst s o urc e 
d oc u m e nts.  T h e e C R Fs will b e m o nit or e d f or c o m pl et e n ess a n d acc ur ac y a g ai nst t h e s o urc e d oc u m e nts 
by t h e C R A(s) o n a r e g ul ar b asis.  I nc o nsist e nci es b et w e e n t h e e C R Fs a n d s o urc e d oc u m e nts will b e 
r es olv e d i n acc or d a nc e wit h t h e pri nci pl es of G C P. 
C o m pl et e d e C R Fs will b e extr act e d fr o m t h e cli nic al d at a b as e, st or e d as P D F fil es o n a C D- R O M a n d s e nt 
t o t h e r es p ectiv e st u dy sit e f or arc hivi n g.  A C D- R O M c o nt ai ni n g all e C R Fs will b e k e pt by t h e S p o ns or i n 
t h e S p o ns or’s Tri al M ast er Fil e. 
7. 4. 2  
Cli nic al D at a M a n a g e m e nt 
D at a fr o m e C R Fs a n d ot h er ext er n al d at a ( e. g., l a b or at or y d at a) will b e e nt er e d i nt o or m er g e d wit h a 
cli nic al d at a b as e as s p ecifi e d i n t h e d at a m a n a g e m e nt pl a n.  Q u alit y c o ntr ol a n d d at a v ali d ati o n 
pr oc e d ur es will b e a p pli e d t o e ns ur e t h e v ali dit y a n d acc ur ac y of t h e cli nic al d at a b as e. 
7. 4. 3  
D at a b as e Q u alit y Ass ur a nc e 
I n acc or d a nc e wit h t h e v e n d or’s  pr oc e d ur es, t h e cli nic al d at a b as e will b e r evi e w e d a n d c h ec k e d f or 
o missi o ns, a p p ar e nt err ors, a n d v al u es r e q uiri n g f urt h er cl arific ati o n usi n g c o m p ut eriz e d a n d m a n u al 
pr oc e d ur es.    D at a q u eri es r e q uiri n g cl arific ati o n will b e d oc u m e nt e d a n d r et ur n e d t o t h e st u dy sit e f or 
r es ol uti o n.  O nly a ut h oriz e d p ers o n n el will m a k e c orr ecti o ns t o t h e cli nic al d at a b as e, a n d all c orr ecti o ns 
wi ll b e d oc u m e nt e d i n a n a u dit tr ail. 
7. 4. 4  
Bi o a n al ytic al D at a M a n a g e m e nt a n d Q u alit y C o ntr ol 
 
 
 
 
 
7. 5  R et e nti o n of  R ec or ds 
T h e I nv esti g at or h as t h e r es p o nsi bilit y t o r et ai n all st u dy “ ess e nti al d oc u m e nts”, as d escri b e d i n I C H E 6.  
Ess e nti al d oc u m e nts i ncl u d e b ut n ot li mit e d t o t h e  pr ot oc ol, c o pi es of p a p er C R Fs or e C R Fs, s o urc e 
d oc u m e nts, l a b or at ory t est r es ults, S M i nv e nt or y r ec or ds, I n v esti g at or's Br oc h ur e, r e g ul at or y a g e nc y 
r e gistr ati o n d oc u m e nts ( e. g., F D A f or m 1 5 7 2, I C Fs, a n d I R B/I E C c orr es p o n d e nc e).  T h e i nv esti g at or 
s h o ul d t a k e m e as ur es t o pr e v e nt acci d e nt al or pr e m at ur e d estr ucti o n of t h es e d oc u m e nts.  St u dy 
ess e nti al d oc u m e nts s h o ul d b e r et ai n e d u ntil at l e ast t w o y e ars aft er t h e l ast a p pr o v al of a m ar k eti n g 
a p plic ati o n or aft er f or m al disc o nti n u ati o n of cli nic al d e v el o p m e nt of t h e i nv esti g ati o n al pr o d uct.  T h es e 
d oc u m e nts s h o ul d b e r et ai n e d f or a l o n g er p eri o d, h o w e v er, if r e q uir e d b y t h e a p plic a bl e r e g ul at or y 
r e q uir e m e nts or by a n a gr e e m e nt wit h t h e S p o ns or.  T h e I nv esti g at or m ust o bt ai n writt e n p er missi o n 
fr o m t h e S p o ns or pri or t o t h e d estr ucti o n of a ny st u dy d oc u m e nt. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
It is r e q u est e d t h at at t h e c o m pl eti o n of t h e r e q uir e d r et e nti o n p eri o d, or s h o ul d t h e I n v esti g at or r etir e 
or r el oc at e, t h e I nv esti g at or c o nt act t h e S p o ns or, all o wi n g t h e S p o ns or t h e o pti o n of p er m a n e ntl y 
r et ai ni n g t h e st u dy r ec or ds. 
T h es e r ec or ds m ust b e m a d e a v ail a bl e at r e as o n a bl e ti m es f or i ns p ecti o n a n d d u plic ati o n, if r e q uir e d, by 
a pr o p erly a ut h oriz e d r e pr es e nt ativ e of t h e U S F D A i n acc or d a nc e wit h t h e U S 2 1 C F R 3 1 2. 6 8 or ot h er 
n ati o n al or f or ei g n r e g ul at or y a ut h oriti es i n acc or d a nc e wit h r e g ul at or y r e q uir e m e nts. 
7. 6  A u diti n g Pr oc e d ur es 
I n a d diti o n t o t h e r o uti n e m o nit ori n g pr oc e d ur es, t h e S p o ns or’s C or p or at e Q u alit y Ass ur a nc e 
d e p art m e nt or q u alifi e d d esi g n e e m a y c o n d uct a u dits of cli nic al r es e arc h acti viti es i n acc or d a nc e wit h 
t h e S p o ns or’s writt e n S O Ps t o e v al u at e c o m pli a nc e wit h t h e pri nci pl es of I C H G C P a n d all a p plic a bl e l oc al 
r e g ul ati o ns.  A g ov er n m e nt r e g ul at ory a ut h ority m a y als o wis h t o c o n d uct a n i ns p ecti o n ( d uri n g t h e 
st u dy or aft er its c o m pl eti o n).  If a n i ns p ecti o n is r e q u est e d by a r e g ul at ory a ut h orit y, t h e I nv esti g at or 
m ust i nf or m t h e S p o ns or a n d t h e C R O i m m e di at ely t h at t his r e q u est h as b e e n m a d e. 
T h es e r ec or ds m ust b e m a d e a v ail a bl e at r e as o n a bl e ti m es f or i ns p ecti o n a n d d u plic ati o n, if r e q uir e d, by 
a pr o p erly a ut h oriz e d r e pr es e nt ativ e of t h e U S F D A i n acc or d a nc e wit h t h e U S 2 1  C F R 3 1 2. 6 8 or ot h er 
n ati o n al or f or ei g n r e g ul at or y a ut h oriti es i n acc or d a nc e wit h r e g ul at or y r e q uir e m e nts. 
7. 7  P u blic ati o n of R es ults 
A ny pr es e nt ati o n or p u blic ati o n of d at a c oll ect e d as a dir ect or i n dir ect r es ult of t his tri al will b e 
c o nsi d er e d as a j oi nt p u blic ati o n b y t h e I nv esti g at or(s) a n d t h e a p pr o pri at e p ers o n n el at t h e S p o ns or’s 
sit e.  A ut h ors hi p will b e d et er mi n e d by m ut u al a gr e e m e nt.  All m a n uscri pts, a bstr acts or ot h er m o d es of 
pr es e nt ati o n arisi n g fr o m t h e r es ults of t h e st u dy m ust b e r evi e w e d a n d a p pr o v e d i n writi n g b y t h e 
S p o ns or, pri or t o s u b missi o n f or p u blic ati o n or pr es e nt ati o n.  N o p u blic ati o n or pr es e nt ati o n wit h 
r es p ect t o t h e st u dy s h all b e m a d e u ntil a ny S p o ns or c o m m e nts o n t h e pr o p os e d p u blic ati o n or 
pr es e nt ati o n h av e b e e n a d dr ess e d t o t h e S p o ns or’s s atisf acti o n.  
T h e d et ail e d o bli g ati o ns r e g ar di n g t h e p u blic ati o n of a ny d at a, m at eri al r es ults, or ot h er i nf or m ati o n, 
g e n er at e d or cr e at e d i n r el ati o n t o t h e st u dy s h all b e o utli n e d i n t h e a gr e e m e nt b et w e e n e ac h 
I nv esti g at or a n d t h e S p o ns or or d esi g n e e. 
7. 8  Fi n a nci n g a n d I ns ur a nc e 
Fi n a nci n g a n d I ns ur a nc e i nf or m ati o n will b e s et f ort h i n a s e p ar at e d oc u m e nt b et w e e n t h e I n v esti g at or 
a n d S p o ns or ( pr ovi d e d b y t h e S p o ns or or d esi g n e e). 
7. 9  Discl os ur e a n d C o nfi d e nti alit y 
T h e c o nt e nts of t his pr ot oc ol a n d a n y a m e n d m e nts a n d r es ults o bt ai n e d d uri n g t h e c o urs e of t his st u dy 
will b e k e pt c o nfi d e nti al b y t h e I nv esti g at or, t h e I nv esti g at or’s st aff, a n d I R B a n d will n ot b e discl os e d i n 
w h ol e or i n p art t o ot h ers or us e d f or a ny p ur p os e ot h er t h a n r evi e wi n g or p erf or mi n g t h e st u dy wit h o ut 
t h e writt e n c o ns e nt of t h e S p o ns or.  N o d at a c oll ect e d as p art of t his st u dy will a p p e ar i n a ny writt e n 
w or k, i ncl u di n g p u blic ati o ns, wit h o ut t h e writt e n c o ns e nt of S p o ns or. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
All p ers o ns assisti n g i n t h e p erf or m a nc e of t his st u dy m ust b e b o u n d b y t h e o bli g ati o ns of c o nfi d e nti alit y 
a n d n o n- us e s et f ort h i n t h e C o nfi d e nti alit y A gr e e m e nt b et w e e n t h e I nv esti g at or a n d S p o ns or. 
7. 1 0  Disc o nti n u ati o n of St u d y 
T h e S p o ns or r es erv es t h e ri g ht t o disc o nti n u e t h e st u dy f or m e dic al or a d mi nistr ati v e r e as o ns at a n y 
ti m e.  T h e I nv esti g at or will b e r ei m b urs e d f or r e as o n a bl e ex p e ns es c ov eri n g s u bj ects, us e of liv e-i n 
f aciliti es, l a b or at ory t ests, a n d ot h er pr of essi o n al f e es.  T h e I nv esti g at or will r ef u n d t h e exc ess of 
p a y m e nts m a d e i n a d v a nc e. 
T h e I nv esti g at or r es erv es t h e ri g ht t o disc o nti n u e t h e st u dy s h o ul d his/ h er j u d g m e nt s o dict at e.  T h e 
I nv esti g at or will n otif y t h e I R B i n c as e of st u dy disc o nti n u ati o n.  St u dy r ec or ds m ust b e r et ai n e d as n ot e d 
a b o v e. 
8  E T HI C S 
8. 1  I nstit uti o n al R e vi e w B o ar ds / I n d e p e n d e nt Et hics C o m mitt e es 
A list of t h e I nstit uti o n al R evi e w B o ar d(s) (I R B) a n d/ or I n d e p e n d e nt Et hics C o m mitt e e(s) (I E C) t h at 
a p pr o v e d t his st u dy a n d t h e a p pr ov al l ett ers will b e i ncl u d e d i n t h e cli nic al st u dy r e p ort f or t his pr ot oc ol. 
T h e pr ot oc ol, a n y pr ot oc ol a m e n d m e nts, a n d t h e i nf or m e d c o ns e nt f or m (I C F) will b e r evi e w e d a n d 
a p pr o v e d b y t h e a p pr o pri at e I R B b ef or e s u bj ects ar e scr e e n e d f or e ntr y.  V erific ati o n of t h e I R B 
u nc o n diti o n al a p pr o v al of t h e pr ot oc ol will b e tr a ns mitt e d t o t h e S p o ns or pri or t o t h e s hi p m e nt of st u dy 
m e dic ati o n t o t h e i nv esti g ati o n al sit e.  T h e I nv esti g at ors or S p o ns or will s u b mit, d e p e n di n g o n l oc al 
r e g ul ati o ns, p eri o dic r e p orts a n d i nf or m t h e I R B of a ny r e p ort a bl e a dv ers e ev e nts ( A Es) p er I nt er n ati o n al 
C o nf er e nc e o n H ar m o niz ati o n (I C H) g ui d eli n es a n d l oc al I R B st a n d ar ds of pr actic e. 
8. 2  Et hic al C o n d uct of t h e St u d y 
T his st u dy will b e c o n d uct e d i n acc or d a nc e wit h st a n d ar d o p er ati n g pr oc e d ur es (S O Ps) of t h e S p o ns or 
a n d  
 t h e C o ntr act R es e arc h Or g a niz ati o ns ( C R O) t h at will c o n d uct t h e st u dy.  T h es e S O Ps ar e 
d esi g n e d t o e ns ur e a d h er e nc e t o G o o d Cli nic al Pr actic e ( G C P) g ui d eli n es as r e q uir e d b y: 
 
D ecl ar ati o n of H elsi n ki, 1 9 6 4 (“ R ec o m m e n d ati o ns G ui di n g P hys ici a ns i n Bi o m e dic al R es e arc h 
I nv olvi n g H u m a n P ati e nts”), a n d all its acc e pt e d a m e n d m e nts t o d at e c o nc er ni n g m e dic al 
r es e arc h i n h u m a ns. 
 
I C H G ui d eli n e f or G C P ( C o m mitt e e f or Pr o pri et ary M e dici n al Pr o d ucts/I C H/ 1 3 5/ 9 5) of t h e 
E ur o p e a n A g e ncy f or t h e Ev al u ati o n of M e dici n al Pr o d ucts, C o m mitt e e f or Pr o pri et ar y M e dici n al 
Pr o d ucts, I C H of P h ar m ac e utic als f or H u m a n Us e. 
 
U nit e d St at es ( U S) C o d e of F e d er al R e g ul ati o ns ( C F R) d e ali n g wit h cli nic al st u di es ( 2 1 C F R, 
i ncl u di n g p arts 5 0 a n d 5 6 c o nc er ni n g P ati e nt I nf or m e d C o ns e nt a n d I R B r e g ul ati o ns). 
 
L oc al, n ati o n al l e g al g ui d eli n es. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
Ar m e nt er os JL, L e wis J E, D av al os M. Ris p eri d o n e a u g m e nt ati o n f or tr e at m e nt-r esist a nt a g gr essi o n i n 
att e nti o n- d eficit/ hy p er activit y dis or d er: A pl ac e b o-c o ntr oll e d pil ot st u dy. J A m Ac a d C hil d A d ol esc 
Ps yc hi atr y 2 0 0 7; 4 6: 5 5 8- 6 5.  
A y el e B T, Li pk o vic h I, M ol e n b er g hs, G, M alli nc kr o dt, C H . A m ulti pl e i m p ut ati o n b as e d a p pr o ac h t o 
s e nsiti vit y a n alys es a n d eff ecti v e n ess ass ess m e nts i n l o n git u di n al cli nic al tri als. J o ur n al of 
Bi o p h ar m ac e utic al St atistics 2 0 1 4; 2 4, 2 1 1- 2 2 8. 
B ar n es T R E. A r ati n g sc al e f or dr u g-i n d uc e d a k at hisi a. Br. J. Psyc hi atr y 1 9 8 9; 1 5 4: 6 7 2- 6 7 6. 
Bl a d er J C, Plisz k a S R, J e ns e n P S, Sc h o ol er N R, K af a nt aris V. P e di atrics 2 0 1 0; 1 2 6( 4): e 7 9 6- 8 0 6. 
C al ar g e C A, Aci o n L, K u p er m a n S et al. W ei g ht g ai n a n d m et a b olic a b n or m aliti es d uri n g ext e n d e d 
ris p eri d o n e tr e at m e nt i n c hil dr e n a n d a d ol esc e nts. J C hil d A d ol esc Psyc h o p h ar m 2 0 0 9; 1 9: 1 0 1-9.  
C h e n Y H, D e M ets DL, L a n K K G. I ncr e asi n g t h e s a m pl e siz e w h e n t h e u n bli n d e d i nt eri m r es ult is 
pr o misi n g. St atistics i n M e dici n e 2 0 0 4; 2 3: 1 0 2 3- 1 0 3 8. 
C o n n or D F, Mc L a u g hli n TJ. A g gr essi o n a n d di a g n osis i n p yc hi atric ally r ef err e d c hil dr e n. C hil d Ps yc hi atr y 
H u m. D e v. 2 0 0 6; 3 7( 1): 1- 1 4. 
F ar m er C A, Ar n ol d L E, B u kst ei n O G, Fi n dli n g RL, G a d o w K D, Li X, B utt er E M, A m a n M G. T h e tr e at m e nt of 
s e v er e c hil d a g gr essi o n ( T OS C A) st u dy: D esi g n c h all e n g es.  C hil d a n d A d ol esc e nt Ps yc hi atry a n d M e nt al 
H e alt h 2 0 1 1; 5: 3 6. 
Fi n dli n g RL, St ei n er H, W ell er E B. Us e of a nti psyc h otics i n c hil dr e n a n d a d ol esc e nts. J. Cli n. Psyc hi atry 
2 0 0 5; 6 6: 2 9- 4 0. 
G a d o w K D, Ar n ol d L E, M oli n a B S et al. Ris p eri d o n e a d d e d t o p ar e nt tr ai ni n g a n d sti m ul a nt m e dic ati o n: 
Eff ects o n att e nti o n- d eficit/ hy p er acti vit y dis or d er, o p p ositi o n al d efi a nt dis or d er, c o n d uct dis or d er, a n d 
p e er a g gr essi o n. . J A m Ac a d C hil d A d ol esc Psyc hi atry 2 0 1 4; 5 3: 9 4 8- 5 9.  
Gr e e n hill LL, B ar m ack J E, S p alt e n D, A n d ers o n M, H al p er n F. M oli n d o n e hy dr oc h ol ori d e i n t h e tr e at m e nt 
of a g gr essiv e, h os pit aliz e d c hil dr e n.  Psyc h o p h ar m ac ol. B ull. 1 9 8 1; 1: 1 2 5- 1 2 7. 
Gr e e n hill LL, S ol o m o n M, Pl e a k R, A m br osi ni P.  M oli n d o n e hy dr oc hl ori d e tr e at m e nt of h os pit aliz e d 
c hil dr e n wit h c o n d uct dis or d er.  J. Cli n. Psyc hi atry 1 9 8 5; 4 6: 2 0- 2 5. 
G uy W.  Cli nic al gl o b al i m pr essi o ns. E C D E U Ass ess m e nt M a n u al f or Psyc h o p h ar m ac ol o gy.  R ock vill e, M D.  
U. S. N ati o n al I nstit ut e of H e alt h, Ps yc h o p h ar m ac ol o gy R es e arc h Br a nc h 1 9 7 6; 2 1 7 -2 2 2.  
H as k ett M E, A h er n L S, W ar d C S, All air e J C. F act or str uct ur e a n d v ali dit y of t h e p ar e nti n g str ess i n d ex-
s h ort fr o m. J. Cli n. C hil d A d ol esc. Psyc h ol. 2 0 0 6; 3 5( 2): 3 0 2- 3 1 2. 
H a ys R D, F ariv ar S S, Li u H. A p pr o ac h es a n d r ec o m m e n d ati o ns f or esti m ati n g mi ni m ally i m p ort a nt 
diff er e nc es f or h e alt h r el at e d q u alit y of lif e m e as ur es. C O P D 2 0 0 5; 2( 1): 6 3 – 6 7. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 7 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
H oc h b er g Y. A s h ar p er B o nf err o ni pr oc e d ur e f or m ulti pl e si g nific a nc e t esti n g. Bi o m etrik a 1 9 8 8; 
7 5( 4): 8 0 0- 8 0 2. 
J e ns e n P S, Y o u n gstr o m E A, St ei n er H, Fi n dli n g RL, M e y er R E, M al o n e R P, C arls o n G A, C occ ar o E F, A m a n 
M G, Bl air J, D o u g h erty D, F erris C, Fly n n L, Gr e e n E, H o a g w o o d K, H utc hi ns o n J, L a u g hr e n T, L e v e L D, 
N o vi ns D K, Viti ell o B. C o ns e ns us R e p ort o n I m p ulsiv e A g gr essi o n as a S y m pt o m Acr oss Di a g n ostic 
C at e g ori es i n C hil d Psyc hi atr y: I m plic ati o ns f or M e dic ati o n St u di es. J. A m. Ac a d. C hil d A d ol esc. Ps yc hi atr y 
2 0 0 7; 4 6 ( 3): 3 0 9- 3 2 2. 
K a uf m a n J, Bir m a h er B, Br e nt D, R a o U, Fly n n C, M or eci P, et al. Sc h e d ul e f or Aff ecti v e Dis or d ers a n d 
Sc hiz o p hr e ni a f or Sc h o ol -A g e C hil dr e n -Pr es e nt a n d Lif eti m e V ersi o n ( K -S A D S -PL): i niti al r eli a bility a n d 
v ali dit y d at a. J A m Ac a d C hil d A d ol esc Psyc hi atry 1 9 9 7; 3 6( 7): 9 8 0 -8.  
K a uf m a n, A S, Lic ht e n b er g er, E. Ass essi n g A d ol esc e nt a n d A d ult I nt elli g e nc e. 3r d E diti o n; 2 0 0 5. 
L a n d gr af J M, A b etz L, W ar e J E. T h e C H Q Us er’s M a n u al. B ost o n. First E diti o n B ost o n, M A: T h e H e alt h 
I nstit ut e, N e w E n gl a n d M e dic al C e nt er  1 9 9 6. 
 
Mc Cl ell a n J, Si kic h L, Fi n dli n g RL, Fr azi er J A, Viti ell o B, Hl ast al a S A, et al. Tr e at m e nt of e arl y -o ns et 
sc hiz o p hr e ni a s p ectr u m disor d ers ( T E O S S): R ati o n al e, d esi g n, a n d m et h o ds. J. A m. Ac a d. C hil d A d ol esc. 
Ps yc hi atr y 2 0 0 7; 4 6: 9 6 9 -9 7 8.  
Mc K ay K E, H al p eri n J M. A D H D, a g gr essi o n, a n d a ntis oci al b e h avi or acr oss t h e lif es p a n. A n n N Y Ac a d Sci 
2 0 0 1; 9 3 1: 8 4- 9 6 . 
M e ht a C R, P oc oc k SJ. A d a pti v e i ncr e as e i n s a m pl e siz e w h e n i nt eri m r es ults ar e pr o misi n g: a pr actic al 
g ui d e wit h e x a m pl es. St atistics i n M e dici n e 2 0 0 0; 0 0: 1- 6.  
T h e M T A C o o p er ativ e Gr o u p. A 1 4- m o nt h r a n d o miz e d cli nic al tri al of tr e at m e nt str at e gi es f or att e nti o n-
d eficit/ hy p er acti vity dis or d er. T h e M T A C o o p er ati v e Gr o u p. M ulti m o d al Tr e at m e nt St u dy of C hil dr e n 
wit h A D H D. Arc h G e n Ps yc hi atr y 1 9 9 9; 5 6: 1 0 7 3- 8 6 . 
M u n etz M R, B e nj a mi n S. H o w t o ex a mi n e p ati e nts usi n g t h e a b n or m al i nv ol u nt ary m ov e m e nt sc al e. 
H os p. C o m m u n. Ps yc hi atr y 1 9 8 8; 3 9: 1 1 7 2- 1 1 7 7. 
P a p p a d o p ul os E, M aci ntyr e II J C, Cris m o n ML et al. Tr e at m e nt r ec o m m e n d ati o ns f or t h e us e of 
a nti ps yc h otics f or a g gr essi v e y o ut h ( T R A A Y). P art II. J A m Ac a d C hil d A d ol esc Ps yc hi atr y 2 0 0 3; 4 2: 1 4 5- 6 1 . 
P e nz n er J B, D u d as M, S ait o E et al. L ac k of eff ect of sti m ul a nt c o m bi n ati o n wit h s ec o n d- g e n er ati o n 
a nti ps yc h otics o n w ei g ht g ai n, m et a b olic c h a n g es, pr ol acti n l e v els, a n d s e d ati o n i n y o ut h wit h cli nic all y 
r el e v a nt a g gr essi o n or o p p ositi o n alit y. J C hil d A d ol esc Psyc h o p h ar m 2 0 0 9; 1 9: 5 6 3-7 3 . 
Plisz k a S, A A C A P W or k Gr o u p o n Q u ality Iss u es. Pr actic e p ar a m et er f or t h e ass ess m e nt a n d tr e at m e nt of 
c hil dr e n a n d a d ol esc e nts wit h att e nti o n- d eficit/ hy p er acti vity dis or d er. J A m Ac a d C hil d A d ol esc 
Ps yc hi atr y 2 0 0 7; 4 6: 8 9 4- 9 2 1 . 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
Plisz k a S R, Cris m o n ML, H u g h es C W et al. T h e T ex as C hil dr e n's M e dic ati o n Al g orit h m Pr oj ect: R e visi o n of 
t h e al g orit h m f or p h ar m ac ot h er a py of att e nti o n- d eficit/ hy p er activit y dis or d er. J A m Ac a d C hil d A d ol esc 
Ps yc hi atr y 2 0 0 6; 4 5: 6 4 2- 5 7.  
P os n er K, Br o w n G K, St a nl ey B, Br e nt D A, Y ers h o v a K V, O q u e n d o M A, C urri er G W, M elvi n G A, Gr e e n hill 
L, S h e n S, M a n n JJ. T h e C ol u m bi a- S uici d e S ev erity r ati n g sc al e: i niti al v ali dit y a n d i nt er n al c o nsist e ncy 
fi n di n gs fr o m t hr e e m ultisit e st u di es wit h a d ol esc e nts a n d a d ults. A m J Psyc hi atry 2 0 1 1; 6 8: 1 2 6 6- 1 2 7 7. 
R atitc h B, O’ K elly , M, T osi ell o, R.  Missi n g d at a i n cli nic al tri als: fr o m cli nic al ass u m pti o ns t o st atistic al 
a n al ysis usi n g p att er n mixt ur e m o d els. P h ar m ac e utic al St atistics, 2 0 1 3; 1 2, 3 3 7- 3 4 7. 
R u bi n D. B.  M ulti pl e I m p ut ati o n f or N o nr es p o ns e i n S ur v e ys, N e w Y or k, Wil ey; 1 9 8 7. 
Sc ott o R os at o N, C orr ell C U, P a p p a d o p ul os E et al. Tr e at m e nt of m al a d a pti v e a g gr essi o n i n y o ut h: C ert 
g ui d eli n es ii. Tr e at m e nts a n d o n g oi n g m a n a g e m e nt. P e di atrics 2 0 1 2; 1 2 9: e 1 5 7 7- 8 6.  
S h elt o n TL, B ar kl ey R A, Cr oss w ait C et al. Ps yc hi atric a n d ps yc h ol o gic al m or bi dit y as a f u ncti o n of 
a d a pti v e dis a bility i n pr esc h o ol c hil dr e n wit h a g gr essiv e a n d hy p er acti v e-i m p ulsiv e-i n att e nti v e b e h avi or. 
J A b n or m C hil d Psyc h ol o gy 1 9 9 8; 2 6: 4 7 5-9 4 . 
Sikic h L, Fr azi er J A, Mc Cl ell a n J et al. D o u bl e- bli n d c o m p aris o n of first- a n d s ec o n d- g e n er ati o n 
a nti ps yc h otics i n e arl y- o ns et sc hiz o p hr e ni a a n d sc hiz o- aff ectiv e dis or d er: Fi n di n gs fr o m t h e tr e at m e nt of 
e arl y- o ns et sc hiz o p hr e ni a s p ectr u m dis or d ers ( T E O S S) st u dy. A m J Ps yc hi atr y 2 0 0 8; 1 6 5: 1 4 2 0- 3 1 . 
Si m ps o n G M, A n g us J W S. A r ati n g sc al e f or extr a pyr a mi d al si d e eff ects.  Act a Psyc hi atr. Sc a n d. S u p pl. 
1 9 7 0; 2 1 2: 1 1- 1 9  
St oc ks J D, T a n ej a B K, B ar ol di P et al. A p h as e 2 a r a n d o miz e d, p ar all el gr o u p, d os e-r a n gi n g st u dy of 
m oli n d o n e i n c hil dr e n wit h att e nti o n- d eficit/ hy p er activit y dis or d er a n d p ersist e nt, s eri o us c o n d uct 
pr o bl e ms. J C hil d A d ol esc Ps yc h o p h ar m 2 0 1 2; 2 2: 1 0 2- 1 1 . 
S w a ns o n J M, Kr a e m er H C, Hi ns h a w S P, Ar n ol d L E, C o n n ers C K, A bi k off H B, et al.  Cli nic al r el ev a nc e of t h e 
pri m ar y fi n di n gs of t h e M T A: S ucc ess r at es b as e d o n s e v erit y of A D H D a n d O D D sy m pt o ms at t h e e n d of 
tr e at m e nt.  J. A m er. Ac a d. C hil d A d ol esc. Psyc hi atry 2 0 0 1; 4 0: 1 6 8- 1 7 9. 
S u p er n us P h ar m ac e utic als, I nc. Si n gl e- C e nt er, Si n gl e- D os e, O p e n-L a b el, R a n d o miz e d, I nc o m pl et e 
Cr oss o v er Pil ot St u dy t o Ev al u at e t h e Si n gl e D os e P h ar m ac o ki n etics of C o ntr oll e d a n d I m m e di at e 
R el e as e F or m ul ati o ns of M oli n d o n e Hy dr oc hl ori d e i n H e alt h y A d ult V ol u nt e ers U n d er F e d a n d F ast e d 
C o n diti o ns 2 0 1 0 .  
S u p er n us P h ar m ac e utic als, I nc St u dy 8 1 0 P 2 0 2. A R a n d o miz e d, D o u bl e- Bli n d, Pl ac e b o- C o ntr oll e d, D os e-
R a n gi n g St u dy t o Ev al u at e t h e Effic acy a n d S af et y of M oli n d o n e Hy dr oc hl ori d e Ext e n d e d- R el e as e T a bl ets 
as A dj u ncti v e T h er a py i n C hil dr e n wit h I m p ulsiv e A g gr essi o n C o m or bi d wit h Att e nti o n-
D eficit/ Hy p er activity Dis or d er ( A D H D) 2 0 1 3. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
S u p er n us P h ar m ac e utic als, I nc St u dy 8 1 0 P 5 0 1. Ps yc h o m etric T esti n g of a n El ectr o nic O bs erv er- R e p ort e d 
O utc o m e M e as ur e of I m p ulsiv e A g gr essi o n of C hil dr e n wit h Att e nti o n D eficit H y p er activit y Dis or d er 
2 0 1 5. 
Viti ell o B, B e h ar D, H u nt, J, St off, D, Ricc uiti, A. S u bty pi n g A g gr essi o n i n C hil dr e n a n d A d ol esc e nts. J. 
N e ur o ps yc hi atr y Cli n. N e ur osci e nc es 1 9 9 0; 2: 1 8 9- 1 9 2. 
Viti ell o B, St off D M. S u bty p es of a g gr essi o n a n d t h eir r el e v a nc e t o c hil d ps yc hi atry. J. A m. Ac a d. C hil d 
Ps yc hi atr y 1 9 9 7; 3 6( 3): 3 0 7- 3 1 5. 
1 0  A P P E N DI C E S 
1 0. 1  A d a pti v e D esi g n Pl a n 
1 0. 1. 1  I ntr o d ucti o n 
T h e d oc u m e nt d efi n es t h e k ey el e m e nts of t h e a d a pti v e d esi g n f or Pr ot oc ol 8 1 0 P 3 0 1 ( A R a n d o miz e d, 
D o u bl e- Bli n d, Pl ac e b o- C o ntr oll e d St u dy t o Ev al u at e t h e Effic ac y a n d S af et y of M oli n d o n e Hy dr oc hl ori d e 
Ext e n d e d- R el e as e T a bl ets f or t h e Tr e at m e nt of I m p ulsi v e A g gr essi o n i n P e di atric S u bj ects wit h Att e nti o n 
D eficit/ Hy p er activity Dis or d er ( A D H D) i n C o nj u ncti o n wit h St a n d ar d A D H D Tr e at m e nt). 
1 0. 1. 2  Tri al D esi g n 
T h e tri al will b e d esi g n e d t o ev al u at e t h e effic ac y a n d s af et y pr ofil es of t w o d os es of S P N- 8 1 0 c o m p ar e d 
t o pl ac e b o.  F or c o m p act n ess, t h e d os es will b e d e n ot e d b y D os e 1 ( 1 8 m g) a n d D os e 2 ( 3 6 m g).  
A t w o-st a g e d esi g n wit h a si n gl e i nt eri m a n alysis a n d fi n al a n al ysis ( F A) will b e utiliz e d i n t his tri al: 
 
St a g e 1 will i ncl u d e s u bj ects w h o c o m pl et e t h e tri al pri or t o t h e I nt eri m A n alysis.   
 
St a g e 2 will i ncl u d e s u bj ects w h o c o m pl et e t h e tri al aft er t h e I nt eri m A n alysis. 
T h e I nt eri m A n alysis d at a will b e r e vi e w e d i n a n u n bli n d e d m a n n er t o p ot e nti all y i ncr e as e t h e n u m b er of 
s u bj ects i n St a g e 2.  T h e s a m pl e siz es i n e ac h st a g e of t h e tri al will b e d e n ot e d as f oll o ws: 
 
L et n 1 d e n ot e t h e t ot al n u m b er of s u bj ects w h o c o m pl et e t h e tri al pri or t o I nt eri m A n al ysis (i n 
ot h er w or ds, t his will b e t h e t ot al s a m pl e siz e i n St a g e 1).  T h e n u m b er of s u bj ects all oc at e d t o 
D os e 1, D os e 2 a n d Pl ac e b o i n St a g e 1 will b e d e n ot e d b y n 1 1, n 1 2 a n d n 1 3, r es p ecti v ely.  N ot e t h at 
n 1 1 + n 1 2 + n 1 3 = n 1 
 
L et n 2 d e n ot e t h e t ot al n u m b er of s u bj ects i n St a g e 2 wit h o ut s a m pl e siz e a dj ust m e nt at I nt eri m 
A n al ysis.  T h e n u m b er of s u bj ects all oc at e d t o D os e 1, D os e 2 a n d Pl ac e b o i n St a g e 2 will b e 
d e n ot e d b y n 2 1, n 2 2 a n d n 2 3, r es p ecti v el y.  N ot e t h at s o m e of t h es e s a m pl e siz es will b e s et t o 0 if 
a d ecisi o n t o dr o p a d osi n g ar m is m a d e at I A a n d n 2 1 + n 2 2 + n 2 3 = n 2. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1. 3  D ecisi o n R ul es at I nt eri m A n al ysis 
As i n dic at e d a b o v e, I nt eri m A n al ysis will b e c o n d uct e d m ai nl y t o s u p p ort a d ecisi o n t o i ncr e as e t h e 
n u m b er of s u bj ects i n St a g e 2 if t h e o bs er v e d tr e at m e nt diff er e nc e f or t h e pri m ar y e n d p oi nt is l ess t h a n 
a ntici p at e d.  It is i m p ort a nt t o n ot e t h at s u bj ect e nr oll m e nt will n ot b e t er mi n at e d i n eit h er d osi n g ar m 
at I nt eri m A n al ysis d u e t o ov er w h el mi n g effic acy a n d, as a c o ns e q u e nc e, n o α will b e s p e nt at I nt eri m 
A n al ysis.  H o w ev er, s u bj ect e nr oll m e nt m a y b e t er mi n at e d d u e t o f utilit y as ex pl ai n e d b el o w. 
I nt eri m A n alysis will b e p erf or m e d aft er a pr e- d efi n e d fr acti o n t h e t ot al n u m b er of s u bj ects c o m pl et e 
t h e tri al, i. e., a p pr oxi m at ely 5 0 % of s u bj ects c o m pl et e t h e fi n al visit. 
T h e f oll o wi n g s a m pl e siz e r e ass ess m e nt r ul e will b e a p pli e d at I nt eri m A n alysis.  L et C P d efi n e t h e d os e-
s p ecific c o n diti o n al p o w er at I nt eri m A n al ysis, i. e., t h e pr o b a bilit y of est a blis hi n g a si g nific a nt tr e at m e nt 
eff ect o n t h e pri m ar y e n d p oi nt c o n diti o n al u p o n t h e pri m ar y e n d p oi nt d at a av ail a bl e at I nt eri m A n al ysis 
u n d er t h e ori gi n al s a m pl e siz e ass u m pti o ns.  I n p artic ul ar, C P 1 is d efi n e d as c o n diti o n al p o w er b as e d o n 
t h e c o m p aris o n of D os e 1 t o pl ac e b o at I nt eri m A n alysis a n d C P 2 is d efi n e d as c o n diti o n al p o w er b as e d 
o n t h e c o m p aris o n of D os e 2 t o pl ac e b o at I nt eri m A n al ysis. 
T h e tri al’s d esi g n will b e m o difi e d at I nt eri m A n al ysis usi n g t h e f oll o wi n g t hr es h ol ds ( C P r ef ers t o eit h er 
C P 1 or C P 2): 
 
If C P < 0. 1, disc o nti n u e s u bj ect e nr oll m e nt i n t his p artic ul ar d osi n g ar m ( e. g., s u bj ects will b e 
all oc at e d t o D os e 2 or pl ac e b o i n St a g e 2 if C P 1 < 0. 1 a n d C P 2 ≥ 0. 1).  
 
If C P ≥ 0. 1 a n d C P ≤ 0. 3 6, r et ai n t h e ori gi n al s a m pl e siz e i n t h e d osi n g ar m. 
 
If C P ≥ 0. 3 6 a n d C P ≤ 0. 8, i ncr e as e t h e s a m pl e siz e i n t h e d osi n g ar m. 
 
If C P > 0. 8, r et ai n t h e ori gi n al s a m pl e siz e i n t h e d osi n g ar m.  
T h e s a m pl e siz e will b e i ncr e as e d i n a d osi n g ar m t o ac hi e v e t h e n o mi n al p o w er of 8 0 % b ef or e t h e 
m ulti plicity a dj ust m e nt or t h e s a m pl e siz e will b e d o u bl e d, w hic h ev er is s m all er. 
T h e f oll o wi n g r ul es will b e a p pli e d t o c o m p ut e t h e s a m pl e siz es acr oss t h e tr e at m e nt ar ms i n St a g e 2:  
 
If a d ecisi o n t o disc o nti n u e s u bj ect e nr oll m e nt is m a d e f or a p artic ul ar d osi n g ar m at I nt eri m 
A n al ysis, s u bj ects w h o w er e pl a n n e d t o b e e nr oll e d i n t h at ar m aft er I nt eri m A n al ysis will b e r e-
distri b ut e d t o t h e r e m ai ni n g tr e at m e nt ar ms.  F or ex a m pl e, if D os e 1 is dr o p p e d a n d D os e 2 is 
r et ai n e d, t h e s a m pl e siz es f or t h e t hr e e tr e at m e nt ar ms i n St a g e 2 will b e d efi n e d as f oll o ws:  
o  D os e 1: 0. 
o  D os e 2: n 2 2 + n 1 2 / 2. 
o  Pl ac e b o: n 2 3 + n 1 2 / 2.  
 
 
If a d ecisi o n is m a d e t o i ncr e as e t h e s a m pl e siz e i n at l e ast o n e d osi n g ar m, t h e m o difi e d s a m pl e 
siz e i n t h e pl ac e b o ar m will b e e q u al t o t h e l ar g er m o difi e d s a m pl e siz e i n t h e t w o d osi n g ar ms.  
F or ex a m pl e, if t h e m o difi e d s a m pl e siz es i n t h e t w o d osi n g ar ms i n St a g e 2 ar e n 3 1 a n d n 3 2, 
r es p ectiv ely, t h e m o difi e d s a m pl e siz e i n t h e pl ac e b o ar m i n St a g e 2 will b e s et t o m ax(n 3 1, n 3 2).  
H o w ev er, if t h e s a m pl e siz e is i ncr e as e d i n o n e d osi n g ar m, t h e s a m pl e siz e i n t h e ot h er d osi n g 
ar m will n ot b e a ut o m atic ally i ncr e as e d. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1. 4  A d a pti v e D esi g n 
T his s ecti o n d efi n es t h e m at h e m atic al a p pr o ac h us e d i n t h e pr o p os e d a d a pti v e d esi g n wit h t w o st a g es 
a n d d at a- dri v e n d ecisi o n r ul es ( e. g., s a m pl e siz e m o dific ati o n at I nt eri m A n alysis).  T h e d eriv ati o n of t h e 
a d a pti v e d esi g n is b as e d o n t h e c o m bi n ati o n f u ncti o n a p pr o ac h a p pli e d i n c o nj u ncti o n wit h t h e cl os ur e 
pri nci pl e, s e e, f or ex a m pl e, W a n g et al. ( 2 0 0 1), Br a n n at h et al. ( 2 0 0 2) a n d H o m m el ( 2 0 0 5).  T his g e n er al 
a p pr o ac h is c o m m o nly us e d t o c o nstr uct a d a ptiv e d esi g ns i n c o nfir m at or y tri als a n d g u ar a nt e es t h at t h e 
o v er all Ty p e I err or r at e is pr ot ect e d i n t h e tri al at t h e n o mi n al l ev el (t w o-si d e d α = 0. 0 5) r e g ar dl ess of 
t h e ty p e of d esi g n m o dific ati o ns at a n I nt eri m A n alysis, i ncl u di n g d ecisi o ns t o dr o p a tr e at m e nt ar m or 
a dj ust t h e s a m pl e siz e i n o n e or m or e ar ms. 
L et H 1 a n d H 2 d e n ot e t h e n ull h y p ot h es es of n o tr e at m e nt eff ect f or t h e t w o d os e- pl ac e b o c o m p aris o ns 
( D os e 1 v ers us pl ac e b o a n d D os e 2 v ers us pl ac e b o).  Acc or di n g t o t h e c o m bi n ati o n f u ncti o n a p pr o ac h, 
t h e a m o u nt of e vi d e nc e t o r ej ect t h es e n ull h y p ot h es es will b e ev al u at e d s e p ar at el y i n e ac h i n di vi d u al 
st a g e of t h e tri al a n d t h e i nf er e nc es at F A will b e p erf or m e d by c o m bi ni n g t h e evi d e nc e acr oss t h e t w o 
st a g es.  F urt h er, t h e r ej ecti o n r ul es f or H 1 a n d H 2 will b e c h os e n t o ac hi e v e c o nsist e nc y wit h t h e 
H oc h b er g pr oc e d ur e ( D mitri e n k o a n d D’ A g osti n o, 2 0 1 3) t h at w as pr e- d efi n e d as m ulti plicity a dj ust m e nt 
t o ol i n t his tri al.  T o ac hi ev e t his c o nsist e nc y, t h e H oc h b er g pr oc e d ur e will b e a p pli e d wit hi n e ac h st a g e 
( H oc h b er g, 1 9 8 8). 
L et p i a n d q i d e n ot e t h e p-v al u es f or t esti n g t h e n ull h y p ot h esis H i, i = 1, 2, b as e d o n t h e d at a i n St a g es 1 
a n d 2, r es p ectiv ely.  T h e St a g e 2 p-v al u es ar e c o m p ut e d fr o m t h e s a m pl es o bt ai n e d aft er I nt eri m 
A n al ysis, i. e., t h e s a m pl e siz e i n a d osi n g ar m m ay b e a dj ust e d.  F urt h er, p ( 1) < p ( 2) will d e n ot e t h e 
or d er e d tr e at m e nt eff ect p-v al u es i n St a g e 1 a n d si mil arly q ( 1) < q ( 2) will d e n ot e t h e or d er e d tr e at m e nt 
eff ect p-v al u es i n St a g e 2.  T h es e p-v al u es will b e us e d t o c o nstr uct a cl os ur e- b as e d r e pr es e nt ati o n of 
t h e H oc h b er g pr oc e d ur e i n e ac h of t h e t w o st a g es.  T o d efi n e t h e cl os ur e- b as e d r e pr es e nt ati o n, a cl os e d 
f a mily of i nt ers ecti o n h y p ot h es es t h at i ncl u d es all p ossi bl e n o n- e m pty i nt ers ecti o ns of t h e t w o n ull 
hy p ot h es es will b e s et u p.  T a bl e 1 a n d T a bl e 2 dis pl ay t h e i nt ers ecti o n hy p ot h es es i n t h e cl os e d f a mily 
a n d ass oci at e d i nt ers ecti o n p-v al u es t h at d efi n e t h e H oc h b er g pr oc e d ur e i n St a g e 1 a n d St a g e 2 
r es p ectiv ely. 
T a bl e 1: I nt ers ecti o n h y p ot h esis a n d H oc h b er g i nt ers ecti o n p- v al u es i n St a g e 1. 
I nt ers ecti o n hy p ot h esis 
H oc h b er g i nt ers ecti o n p -v al u e  
H 1 ∩ H 2  
p 1 2 = mi n ( 2 p ( 1) , p ( 2)) 
H 1 
p 1 
H 2 
p 2 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
T a bl e 2: I nt ers ecti o n h y p ot h esis a n d H oc h b er g i nt ers ecti o n p- v al u es i n St a g e 2. 
I nt ers ecti o n hy p ot h esis 
H oc h b er g i nt ers ecti o n p -v al u e  
H 1 ∩ H 2  
q 1 2 = mi n ( 2 q ( 1) , q ( 2)) 
H 1 
q 1 
H 2 
q 2 
 
N ot e t h at, if a c ert ai n d os e is dr o p p e d d u e t o f utilit y at I nt eri m A n al ysis, t h e c orr es p o n di n g p-v al u es i n 
St a g e 2 is a ut o m atic ally s et t o 1 t o r e m ov e t h e d osi n g ar m fr o m c o nsi d er ati o n.  T his g u ar a nt e es t h at a 
n ull h y p ot h esis c a n n ot b e r ej ect e d at F A if t h e c orr es p o n di n g d os e w as dr o p p e d d u e t o f utilit y at I nt eri m 
A n al ysis.  F urt h er, t h e p-v al u es c o m p ut e d at I nt eri m A n al ysis ( St a g e 1 p-v al u es) ar e n ot us e d f or 
i nf er e nti al p ur p os es a n d t h er ef or e n o α will b e s p e nt at I nt eri m A n al ysis t o st o p t h e tri al e arl y d u e t o 
o v er w h el mi n g effic ac y. 
As a n ill ustr ati o n, if D os e 1 is dr o p p e d at I nt eri m A n alysis, t h e c orr es p o n di n g tr e at m e nt eff ect p-v al u e i n 
St a g e 2 ( q 1) will b e s et t o 1.  As a r es ult, t h e i nt ers ecti o n p- v al u es will b e d efi n e d i n St a g e 2 as s h o w n i n 
T a bl e 3 ( n ot e t h at t h e s m all er or d er e d p-v al u e will b e e q u al t o q 2 a n d t h e l ar g er or d er e d p-v al u e will b e 
e q u al t o 1). 
T a bl e 3: I nt ers ecti o n h y p ot h es es a n d H oc h b er g i nt ers ecti o n p- v al u es i n St a g e 2 if d os e 1 is dr o p p e d at 
I nt eri m A n al ysis. 
I nt ers ecti o n hy p ot h esis 
H oc h b er g i nt ers ecti o n p -v al u e  
H 1 ∩ H 2  
q 1 2 = mi n ( 2 q 2 , 1 ) 
H 1 
1  
H 2 
q 2 
 
T h e i nf er e nc es f or t h e t w o n ull h y p ot h es es will b e p erf or m e d at F A usi n g t h e c o m p osit e tr e at m e nt 
eff ect p-v al u es t h at will b e d efi n e d as f oll o ws.  L et w 1 a n d w 2 d efi n e t h e st a g e w ei g hts t h at ar e 
pr os p ectiv ely d efi n e d b as e d o n t h e ex p ect e d a m o u nt of i nf or m ati o n at I nt eri m A n al ysis.  Si nc e I nt eri m 
A n al ysis is pl a n n e d t o b e t ak e n aft er 5 0 % of t h e s u bj ects h a v e c o m pl et e d t h e tri al, 
n 1 (t ot al s a m pl e siz e i n St a g e 1) = n 2 (t ot al s a m pl e siz e i n St a g e 2 b ef or e s a m pl e siz e a dj ust m e nt), 
a n d t h us t h e pr e-s p ecifi e d st a g e w ei g hts ar e gi v e n b y  

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
w 1 =
n 1
n 1 + n 2
= 0. 5 , w 2 =
n 2
n 1 + n 23
= 0. 5 . 
Usi n g t h e st a g e w ei g hts, t h e c o m bi n ati o n f u ncti o n t o b e us e d at F A will b e d efi n e d as f oll o ws: 
 
 
w h er e (x) is t h e c u m ul ativ e distri b uti o n f u ncti o n of t h e st a n d ar d n or m al distri b uti o n.   
T his c o m bi n ati o n f u ncti o n will b e a p pli e d t o c o m p ut e c o m p osit e i nt ers ecti o n p-v al u es f or e ac h 
i nt ers ecti o n hy p ot h esis i n t h e cl os e d f a mily.  T h e r es ulti n g c o m p osit e i nt ers ecti o n p-v al u es ar e d e n ot e d 
by r1 2, r1, r2, a n d ar e d efi n e d i n T a bl e 4. 
T a bl e 4: I nt ers ecti o n h y p ot h esis a n d c o m p osit e i nt ers ecti o n p- v al u es at F A. 
I nt ers ecti o n hy p ot h esis 
C o m p osit e i nt ers ecti o n p -v al u e  
H 1 ∩ H 2  
r1 2 = c(p 1 2, q 1 2) 
H 1 
r1  = c(p 1, q 1) 
H 2 
r2 = c(p 2, q 2) 
 
Aft er t h at, t h e n ull h y p ot h esis H 1 will b e r ej ect e d at F A ( w hic h i m pli es a st atistic ally si g nific a nt tr e at m e nt 
eff ect at D os e 1) if t h e c o m p osit e p-v al u es f or all i nt ers ecti o n h y p ot h es es i n t h e cl os e d f a mily t h at 
c o nt ai n H 1 ar e si g nific a nt at  = 0. 0 5 (t w o-si d e d), i. e.,   
r1 2 ≤  a n d r1 ≤  
Si mil arly, t h e n ull hy p ot h esis H 2 will b e r ej ect e d at F A ( a n d a st atistic ally si g nific a nt tr e at m e nt eff ect will 
b e est a blis h e d at D os e 2) if t h e c o m p osit e p-v al u es f or all i nt ers ecti o n h y p ot h es es i n t h e cl os e d f a mily 
t h at c o nt ai n H 2 ar e si g nific a nt at  = 0. 0 5, i. e.,   
r1 2 ≤  a n d r2 ≤  
As i n dic at e d a b o v e, t h e r es ulti n g a p pr o ac h acc o u nts f or t w o s o urc es of m ulti plicit y i n t his cli nic al tri al 
( m ulti pl e d at a l o oks a n d m ulti pl e d os e- pl ac e b o c o m p aris o ns) a n d g u ar a nt e es T y p e I err or r at e c o ntr ol at 
α  = 0. 0 5.  T h e α  c o ntr ol is r et ai n e d ev e n if t h e s a m pl e siz e is a dj ust e d i n or m or e tr e at m e nt ar ms at 
I nt eri m A n alysis.  I n a d diti o n, it n e e ds t o b e e m p h asiz e d t h at a n ull h y p ot h esis c a n n ot b e r ej ect e d at F A 
if t h e c orr es p o n di n g d os e w as dr o p p e d d u e t o f utilit y at I nt eri m A n alysis. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1. 5  I m p ort a nt I nt eri m A n al ysis C o nsi d er ati o ns 
1 0. 1. 5. 1  R es p o nsi bl e P art y 
T h e I nt eri m A n alysis will b e p erf or m e d b y a n i n d e p e n d e nt u n bli n d e d st atistici a n w h o is n ot affili at e d t o 
t h e tri al s p o ns or, tri al m a n a g e m e nt, d at a cl e a ni n g, a n d a n alysis. 
T h e H e a d of Cli nic al R es e arc h a n d Dir ect or of Bi ost atistics at S u p er n us (s p o ns or) will r ec ei v e 
r ec o m m e n d ati o n l ett er fr o m t h e i n d e p e n d e nt u n bli n d e d st atistici a n.  T h e y will m a k e t h e fi n al d ecisi o n 
f or t h e s a m pl e siz e a dj ust m e nt. 
1 0. 1. 5. 2  C o nfi d e nti alit y 
T h e i n d e p e n d e nt st atistici a n will si g n t h e c o nfi d e nti alit y a gr e e m e nt.  H e/s h e will n ot r ev e al a ny 
u n bli n d e d d at a/i nf or m ati o n t o a ny p ers o ns wit hi n his/ h er o w n or g a niz ati o n or t o t h e s p o ns or, wit h t h e 
exc e pti o n of s e n di n g r ec o m m e n d ati o n as d escri b e d i n S ecti o n 1 0. 1. 5. 1  a b o v e. 
R ef er e nc es 
Br a n n at h W, P osc h M, B a u er P. R ec ursiv e c o m bi n ati o n t ests. J o ur n al of t h e A m eric a n St atistic al 
Ass oci ati o n. 2 0 0 2; 9 7: 2 3 6- 2 4 4. 
D mitri e n k o, A., D’ A g osti n o, R. B. T ut ori al i n Bi ost atistics: Tr a diti o n al m ulti plicity a dj ust m e nt m et h o ds i n 
cli nic al tri als. St atistics i n M e dici n e. 2 0 1 3; 3 2: 5 1 7 2- 5 2 1 8. 
H o m m el, G. A d a ptiv e m o dific ati o ns of hy p ot h es es aft er a n i nt eri m a n al ysis. Bi o m etric al J o ur n al. 2 0 0 5; 5: 
5 8 1- 5 8 9. 
W a n g, SJ, H u n g H MJ, Ts o n g Y, C ui L. Gr o u p s e q u e nti al t est str at e gi es f or s u p eri orit y a n d n o n-i nf eri orit y 
hy p ot h es es i n activ e c o ntr oll e d cli nic al tri als. St atistics i n M e dici n e. 2 0 0 1; 2 0: 1 9 0 3- 1 9 1 2. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 2  R etr os p ecti v e M o difi e d O v ert A g gr essi o n Sc al e ( R- M O A S)  
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 8 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 3  Cli nic al Gl o b al I m pr essi o n ( C GI) Sc al e 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 4  Viti ell o Sc al e 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 5  Ki d di e- S a ds- Pr es e nt a n d Lif eti m e V ersi o n ( K- S A D S- PL) 2 0 1 3  
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 9 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 0 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 1 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 2 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 3 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 4 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 5 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 6 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 7 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 8 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 1 9 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 6  C ol u m bi a- S uici d e S e v erit y R ati n g Sc al es ( C- S S R S) 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 0 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 7  S w a ns o n, N ol a n a n d P el h a m R ati n g Sc al e- R e vis e d ( S N A P I V) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 8  Si m ps o n- A n g us R ati n g Sc al e 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 
1 0. 9  B ar n es A k at hisi a R ati n g Sc al e ( B A R S) 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1 0  A b n or m al I n v ol u nt ar y M o v e m e nt Sc al e ( AI M S) 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 8  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 1 9  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 0  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 1  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1 1  C hil d H e alt h Q u esti o n n air e P ar e nt F or m 2 8-it e m ( C H Q- P F 2 8) 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 2  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 3  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 4  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 5  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
1 0. 1 2  P ar e nti n g Str ess I n d e x- S h ort F or m ( P SI- 4- S F) 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 6  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy. 
 

S u p er n us ® P h ar m ac e utic als, I nc.  
C O N FI D E N TI AL 
 
8 1 0 P 3 0 1                                                                   V ersi o n 9. 0                                               P a g e 2 2 7  of 2 2 7  
 
T his d oc u m e nt is c o nfi d e nti al.  It c o nt ai ns pr o pri et ary i nf or m ati o n of S u p er n us ® P h ar m ac e utic als, I nc.  A ny vi e wi n g or discl os ur e 
of s uc h i nf or m ati o n t h at is n ot a ut h oriz e d i n writi n g by t h e S p o ns or is strictly pr o hi bit e d.  S uc h i nf or m ati o n m a y b e us e d s ol ely 
f or t h e p ur p os e of r evi e wi n g or p erf or mi n g t his st u dy.