Clinical trial NCT02635035
Conditions: Attention Deficit Disorder Attention Deficit Hyperactivity Disorder
Sponsor: NYU Langone Health
Start date: 2015-11-01; Completion date: 2019-01-09
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The primary purpose of this study is to test the efficacy of Lisdexamfetamine in Adults With Attention Deficit Hyperactivity Disorder (ADHD) and Sluggish Cognitive Tempo (SCT). This is a placebo controlled, cross-over clinical trial of oral Lisdexamfetamine Dimesylate 30-70mg/day in adults with attention-deficit hyper-activity disorder and Sluggish Cognitive Tempo (ACT). Patients will be assigned either LDX/Placebo for 10 weeks with a two week placebo washout period.

Detailed description:
Sluggish Cognitive Tempo (SCT) describes individuals who are dreamy, spacey, slow moving, hyper active, have difficulty initiating tasks, and often seem under-motivated and under-aroused. Barkley identified nine cardinal symptoms of SCT: 1) prone to daydreaming instead of concentrating; 2) trouble staying alert/awake in boring situations; 3) being easily confused; 4) being easily bored; 5) feeling spacey/in a fog; 6) frequently feeling lethargic; 7) being under-active/having less energy than others; 8) being slow moving; 9) not processing information quickly/accurately. Individuals were identified as SCT if they had at least 5 of 9 symptoms rated often or very often on the 9-item SCT subscale from the Barkley Adult ADHD Rating Scale-IV: Self-Report (BAARS-IV; hereafter called the Barkley SCT Scale).

This is a 2 Site (NYU and Mount Sinai) Study of LDX in 50 adults with Attention Deficit Disorder (ADHD) and Sluggish Cognitive Tempo (SCT). The study will be a double-blind, 10-week, cross-over treatment trial of LDX (4 weeks; 30 - 70 mg/day) vs. placebo (4 weeks) with an intervening single- blind placebo washout period (2 weeks). During the LDX treatment period, LDX treatment will be initiated at a dose of 30mg/day at Visit 0 and can be titrated up (in the judgment of the investigator) in increments of 20mg, based upon clinical response and tolerability, to 50mg/day at Visit 1 and 70mg/day at Visit 2. Subjects receiving daily doses of 50mg or 70mg of LDX will be allowed to down titrate one dosage step of 20mg during Visits 2-4 if (in the judgment of the investigator) they are having issues in tolerability. The highest effective dose of LDX will then be maintained until Visit 4. Patients will be seen weekly throughout the trial except during placebo washout.

Arms: arm 1: In this crossover study design, participants assigned to this group will receive Lisdexamfetamine first, then placebo second arm 2: In this crossover study design, participants assigned to this group will receive placebo first, then Lisdexamfetamine second
Interventions: intervention 1: Lisdexamfetamine intervention 2: Placebo
Intervention descriptions: intervention 1: Vyvanse (Lisdexamfetamine Dimesylate) manufactured by Shire, is a Drug Enforcement Administration (DEA) class two,sympathomimetic amine, used for the treatment of attention-deficit hyperactivity disorder. The initial adult dosage is 30mg with allowed adjustments in increments of 10mg or 20mg at weekly intervals. Subjects are initiated on these doses and then they were titrated up by 20mg with a maximum dose of 70mg. intervention 2: Placebo looks just like Vyvanse but has no active ingredients, like a sugar pill.

Protocol documents:
Prot_SAP_000.pdf: 
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Cli ni c al R e s e ar c h Pr ot o c ol
E F FI C A C Y  O F  LI S D E X A M F E T A MI N E  I N A D U L T S  WI T H  A D H D  A N D  
S L U G GI S H C O G NI TI V E T E M P O
A  p h as e  II, r a n d o mi z e d, d o u bl e- bli n d,  cr oss- o v er,  m ulti-c e nt er  st u dy  of  t h e eff ects  of  
V y v a ns e  ( L D X) vs.  pl ac e b o  wit h  a n  i nt er v e ni n g si n gl e- bli n d pl ac e b o  w as h o ut  p eri o d  o n  
p ati e nts  wit h  A d ult  Att e nti o n  D eficit  H y p er acti vit y  Dis or d er  ( A D H D) a n d  Sl u g gis h  
C o g niti v e  T e m p o  ( S C T)
P ri n ci p al  I n v e sti g at o r :
L e n ar d  A dl er,  M. D.
D e p art m e nt  of  Ps yc hi atr y  
O n e  P ar k  A v e n u e,  8t h  
Fl o or  N e w  Y or k,  N Y  
1 0 0 1 6
F a x:  2 1 2- 2 6 3- 7 4 6 0
F u n di n g S p o n s o r:
S hir e  D e v el o p m e nt  
L L C  Gl o b al  M e dic al  
Aff airs
7 2 5  C h est er br o o k  
B o ul e v ar d
W a y n e,  P A  1 9 0 8 7  
Att n:  J o e K er k eri n g
St u d y  P r o d u ct:
Lis d e x a mf et a mi n e  Di m es yl at e  ( L D X), V y v a ns e
P r ot o c ol  N u m b e r:
S 1 3- 0 1 2 8 8
I N D N u m b e r:
I N D n ot  r e q uir e d
P a g e 1
N C T 0 2 6 3 5 0 3 5
NCT02635035


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S T U D Y  S U M M A R Y............................................................................................................................... 1 0
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B A C K G R O U N D ................................................................................................................................................ 1 1
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IN V E S TI G A TI O N A L  A G E N T ............................................................................................................................ 1 1
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P R E C LI NI C A L  D A T A ...................................................................................................................................... 1 2
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C LI NI C A L  D A T A  T O  D A T E ............................................................................................................................. 1 3
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D O S E  R A TI O N A L E ......................................................................................................................................... 1 3
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R E S E A R C H  R I S K S &  B E N E FI T S .................................................................................................................... 1 4
1. 6. 1
Ris k  of  St u d y  Dr u g..........................................................................................................................
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1. 6. 2
Ot h er  Ris ks  of  St u d y  P artici p ati o n........................................................................................... 1 6
1. 6. 3
P ot e nti al  b e n efits............................................................................................................................ 1 7
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S T U D Y  O BJ E C TI V E S...................................................................................................................... 1 7
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S T U D Y  D E SI G N...............................................................................................................................
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3. 1
G E N E R A L  D E SI G N ..........................................................................................................................................
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S E C O N D A R Y  S T U D Y  E N D P OI N T S ................................................................................................................. 2 0
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P RI M A R Y  S A F E T Y  E N D P OI N T S ..................................................................................................................... 2 0
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S U BJ E C T  S E L E C TI O N  A N D  WI T H D R A W A L............................................................................ 2 0
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IN C L U SI O N  C RI T E RI A .................................................................................................................................... 2 0
4. 2
E X C L U SI O N  C RI T E RI A ................................................................................................................................... 2 1
4. 3
S U BJ E C T  R E C R UI T M E N T  A N D  S C R E E NI N G .................................................................................................. 2 1
4. 4
E A R L Y  W I T H D R A W A L O F  S U BJ E C T S ........................................................................................................... 2 2
4. 4. 1
D at a  C oll ecti o n  a n d  F oll o w- u p  f or Wit h dr a w n  S u bj ects................................................. 2 3
5
S T U D Y  D R U G..................................................................................................................................
2 3
5. 1
D E S C RI P TI O N .................................................................................................................................................
2 3
5. 2
T R E A T M E N T  R E GI M E N ................................................................................................................................. 2 3
5. 3
M E T H O D  F O R  A S SI G NI N G  S U BJ E C T S  T O  T R E A T M E N T  G R O U P S ............................................................... 2 4
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P R E P A R A TI O N  A N D  A D MI NI S T R A TI O N  O F  S T U D Y  D R U G .......................................................................... 2 4
5. 5
S U BJ E C T  C O M P LI A N C E  M O NI T O RI N G ......................................................................................................... 2 5
5. 6
P RI O R  A N D  C O N C O MI T A N T  T H E R A P Y ........................................................................................................ 2 5
5. 7
P A C K A GI N G ....................................................................................................................................................
2 6
5. 8
B LI N DI N G  O F  S T U D Y  D R U G ..........................................................................................................................2 6
5. 9
R E C EI VI N G , S T O R A G E , D I S P E N SI N G A N D  R E T U R N .................................................................................... 2 6
5. 9. 1
R ec ei pt  of  Dr u g  S u p pli es............................................................................................................ 2 7
5. 9. 2
St or a g e...............................................................................................................................................
2 7
5. 9. 3
Dis p e nsi n g  of  St u d y  Dr u g.......................................................................................................... 2 7
5. 9. 4
R et ur n  or  D estr ucti o n  of  St u d y  Dr u g.................................................................................... 2 7
6
S T U D Y  P R O C E D U R E S................................................................................................................... 2 7
6. 1
VI SI T  1.......................................................................................................................................................... 2 9
6. 2
VI SI T  2.......................................................................................................................................................... 2 9
6. 3
VI SI T S  3, 4, & 5.........................................................................................................................................
3 0
6. 4
VI SI T  6..........................................................................................................................................................
3 0
6. 5
T E L E P H O N E VI SI T.................................................................................................................................. 3 0
6. 6
VI SI T 7..........................................................................................................................................................
3 0
6. 7   VI SI T S  8, 9, & 1 0.......................................................................................................................................
3 0
6. 8    T E L E P H O N E VI SI T.................................................................................................................................. 3 0
    6. 9    VI SI T  1 1 … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … . 3 1
7
S T A TI S TI C A L  P L A N...................................................................................................................... 3 1
7. 1
S A M P L E  S I Z E D E T E R MI N A TI O N ................................................................................................................... 3 1
7. 2
S T A TI S TI C A L  M E T H O D S ............................................................................................................................... 3 2
7. 3
S U BJ E C T  P O P U L A TI O N (S ) F O R  A N A L Y SI S ................................................................................................... 3 3
8
S A F E T Y  A N D  A D V E R S E  E V E N T S................................................................................................ 3 3
8. 1
D E FI NI TI O N S ..................................................................................................................................................
3 3
8. 2
R E C O R DI N G  O F  A D V E R S E  E V E N T S .............................................................................................................. 3 7
8. 3
R E P O R TI N G  O F  S E RI O U S  A D V E R S E  E V E N T S  A N D  U N A N TI CI P A T E D  P R O B L E M S ..................................... 3 7
8. 3. 1
I n v esti g at or r e p orti n g: n otif yi n g  t h e st u d y s p o ns or...................................................... 3 8
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8. 3. 2
I n v esti g at or r e p orti n g: n otif yi n g  t h e I R B............................................................................ 4 0
8. 3. 3
S p o ns or  r e p orti n g: N otif yi n g  t h e F D A.................................................................................. 4 1
8. 3. 4
S p o ns or  r e p orti n g: N otif yi n g  p artici p ati n g  i n v esti g at ors.............................................. 4 3
8. 4
U N B LI N DI N G  P R O C E D U R E S .......................................................................................................................... 4 3
8. 5
S T O P PI N G  R U L E S ...........................................................................................................................................
4 3
8. 6
M E DI C A L  M O NI T O RI N G ................................................................................................................................ 4 4
9
D A T A  H A N D LI N G  A N D  R E C O R D  K E E PI N G............................................................................. 4 5
9. 1
C O N FI D E N TI A LI T Y .........................................................................................................................................
4 5
9. 2
C O N FI D E N TI A LI T Y  A N D  HI P A A.................................................................................................................. 4 5
9. 3
S O U R C E  D O C U M E N T S ................................................................................................................................... 4 6
9. 4
C A S E  R E P O R T  F O R M S ................................................................................................................................... 4 6
9. 5
R E C O R D S  R E T E N TI O N .................................................................................................................................. 4 7
1 0
S T U D Y  M O NI T O RI N G,  A U DI TI N G,  A N D  I N S P E C TI N G........................................................ 4 7
1 0. 1
S T U D Y  M O NI T O RI N G  P L A N ........................................................................................................................ 4 7
1 0. 2
A U DI TI N G  A N D  IN S P E C TI N G ....................................................................................................................... 4 7
1 1
E T HI C A L  C O N SI D E R A TI O N S.................................................................................................... 4 8
1 2
S T U D Y  FI N A N C E S........................................................................................................................ 4 2
1 2. 1
F U N DI N G  S O U R C E .......................................................................................................................................
4 8
1 2. 2
C O N F LI C T  O F  IN T E R E S T ............................................................................................................................. 4 9
1 2. 3
S U BJ E C T  S TI P E N D S  O R  P A Y M E N T S ...........................................................................................................4 9
1 3
P U B LI C A TI O N  P L A N................................................................................................................... 4 9
1 4
R E F E R E N C E S.................................................................................................................................
5 0
  1 5 A T T A C H M E N T S................................................................................................................................................
5 3
P a g e 4


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Li st of  A b b r e vi ati o n s
A b b r e vi ati o n
D efi niti o n
%
P erc e ntil e
A C D S
A d ult  Cli nici a n  Di a g n ostic  Sc al e
A D D
Att e nti o n  D eficit  Dis or d er
A D H D
Att e nti o n  D eficit  H y p er acti vit y  Dis or d er
A D H D- C
Att e nti o n  D eficit  H y p er acti vit y  Dis or d er  C o m bi n e d  t y p e
A D H D- HI
Att e nti o n  D eficit  H y p er acti vit y  Dis or d er- H y p er acti v e  I m p ulsi v e t y p e
A D H D-I
Att e nti o n  D eficit  H y p er acti vit y  Dis or d er-I n att e nti v e  t y p e
A E
A d v ers e  E v e nts
A D H D- R S
A D H D  R ati n g  Sc al e
A M P
A m p h et a mi n e
A S T
Att e nti o n S witc hi n g T as k
B A R R S
B ar kl e y  S C T  Sc al e
B FI S
B ar kl e y  F u ncti o n al  I m p air m e nt Sc al e
B P
Bl o o d  Pr ess ur e
b p m
B e ats  p er  mi n ut e
B RI E F- A
B e h a vi or  R ati n g  I n v e nt or y of  E x ec uti v e  F u ncti o n ® – A d ult  V ersi o n
C A N T A B
C a m bri d g e  N e ur o ps yc h ol o gic al  T esti n g  A ut o m at e d  B att er y
C R F
C as e  R e p ort  F or m
C GI-I S
Cli nic al  Gl o b al  I m pr essi o ns-I m p air m e nt sc al e
CI
C o nfi d e nc e  I nt er v al
P a g e 5


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A b b r e vi ati o n D e fi niti o n
C- S S R S
C ol u m bi a- S uici d e  S e v erit y  R ati n g  Sc al e
C M
C o nc o mit a nt  M e dic ati o ns
C T
Cli ni c al Tri al
C P O E
C o m p ut e ri z e d P h ysici a n  Or d er  E ntr y  s yst e m
d /c’ d
Di sc o nti n u e d
D E A
Dr u g  E nf orc e m e nt  A d mi nistr ati o n
D R
D o s e R el at e d
D S M
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
D S M-I V
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  4 t h e d iti o n
E C G
El ec tr oc ar di o gr a p h
E P I C
El ec tr o nic M e dic al  H e alt h  R ec or ds
f/ u
F o ll o w u p
F D A
F o o d  &  Dr u g  A d mi nistr ati o n
fr e q
Fr e q u e nc y
G E E
G e n er ali z e d  Esti m ati n g  E q u ati o n
G L M
G e n er al  Li n e ar  M o d el
H I P A A
H e alt h  I ns ur a nc e P ort a bilit y  a n d  Acc o u nt a bilit y  Act  o f 1 9 9 6
I R
I m m e di at e R el e as e
I D S
I n v esti g ati o n al Dr u g  S er vic e
k g
Kil o gr a m
L D X
Li s d e x a mf et a mi n e Di m es yl at e
L T
L o n g-t er m
M A O
M o n o a mi n e  O xi d as e
P a g e 6


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A b b r e vi ati o n D e fi niti o n
M A OI
M o n o a mi n e  O xi d as e  I n hi bit ors
M A S
Mi x e d A m p h et a mi n e S alts
M A S  X R
Mi x e d  A m p h et a mi n e  S alts  E xt e n d e d  R el e as e
MI
M y o c ar di al I nf arcti o n
MI NI
Mi ni  I nt er n ati o n al N e ur o ps yc hi atric I nt er vi e w
m g
Milli gr a m
m m H g
Milli m et ers  of  M erc ur y
M P H
M e t h yl p h e ni d at e
O N - T O P
O n  Ti m e  M a n a g e m e nt,  Or g a niz ati o n,  a n d  Pl a n ni n g O N- T O P
Q T c
Q  T  I nt er v al
R C T
R a n d o mi z e d  C o ntr oll e d  Tri al
S C T
Sl u g gis h  C o g niti v e  T e m p o
sti m
Sti m ul a nt
W AI S-I V
W ec hsl er  A d ult  I nt elli g e nc e Sc al e-I V
P a g e 7


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St u d y  S u m m a r y
Titl e
E F FI C A C Y  O F  LI S D E X A M F E T A MI N E  I N A D U L T S  WI T H  A D H D  A N D  
S L U G GI S H  C O G NI TI V E  T E M P O
S h ort  Titl e
S hir e  S C T
Pr ot oc ol  N u m b er
S 1 3- 0 1 2 8 8
P h as e
Cli nic al  st u d y p h as e  2
M et h o d ol o g y
A  p h as e  II, r a n d o miz e d, d o u bl e- bli n d,  cr oss- o v er, m ulti-c e nt er  st u dy  
of  t h e eff ects  of  V y v a ns e  ( L D X) vs.  pl ac e b o  wit h  a n  i nt er v e ni n g 
si n gl e- bli n d pl ac e b o  w as h o ut  p eri o d  o n  p ati e nts  wit h  A d ult  D eficit  
H y p er acti vit y  Dis or d er  ( A D H D) a n d  Sl u g gis h  C o g niti v e  T e m p o   
( S C T).
St u d y  D ur ati o n
1 3  w e e ks
St u d y  C e nt er(s)
M ulti-c e nt er;  N Y U  a n d  M o u nt  Si n ai
O bj ecti v es
T o  e x a mi n e  t h e eff ects  of  V y v a ns e  ( L D X) vs.  pl ac e b o  wit h  a n  
i nt er v e ni n g si n gl e- bli n d pl ac e b o  w as h o ut  p eri o d o n  p ati e nts  wit h  
A d ult  D eficit  H y p er acti vit y  Dis or d er( A D H D)  a n d  Sl u g gis h  C o g niti v e  
T e m p o( S C T).
N u m b er  of  S u bj ects
1 2 0  a d ults  ( 2 0 % scr e e n f ail r at e), will  b e  r ecr uit e d t o e v al u at e  at t h e  
scr e e ni n g visit  a p pr o xi m at el y  1 0 0  a d ults  wit h  A D H D  at  t w o sit es 
( N Y U a n d  M o u nt  Si n ai)  t o i d e ntif y 5 0  S C T +  a n d  5 0  S C T-.
Di a g n osis  a n d  M ai n  
I ncl usi o n Crit eri a
T h e  st u d y p o p ul ati o n  will  c o nsist of  m al e  a n d  fe m al e o ut p ati e nts  
b et w e e n  1 8  a n d  6 0  y e ars  of  a g e, i ncl usi v e,  wit h  a  Pri m ar y  di a g n osis  
of  A D H D  acc or di n g  t o 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,  F o urt h  E diti o n,  T e xt  R e visi o n  ( D S M-I V- T R) 1 6  crit eri a as  
d et er mi n e d  b y  t h e A d ult  Cli nici a n  Di a g n ostic  Sc al e  v ersi o n  1. 2  
( A C D S v 1. 2).
P a g e 8


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St u d y  Pr o d uct,  
D os e,  R o ut e,  
R e gi m e n
Lis d e x a mf et a mi n e  Di m es yl at e  ( L D X), V y v a ns e.  Pl ac e b o  c o ntr oll e d 
cr oss- o v er st u d y of  or al,  L D X  3 0- 7 0  m g / d a y  i n S C T +  a d ults.
P artici p a nts  t a ki n g pr o hi bit e d  c o nc o mit a nt m e dic ati o ns,  i ncl u di n g 
A D H D  m e dic ati o ns,  will  b e  r e q uir e d t o w as h o ut  of  t h eir m e dic ati o n  
d uri n g  t h e scr e e ni n g p h as e.  T h e  w as h o ut  p eri o d  will  b e  o n e  w e e k  
f or ps yc h osti m ul a nts  a n d  t hr e e w e e ks  f or n o n-sti m ul a nts.
D ur ati o n  of  
a d mi nistr ati o n
P ati e nts  will  b e assi g n e d  eit h er  L D X / Pl ac e b o  f or 1 0  w e e ks  wit h  a  
t w o w e e k  pl ac e b o  w as h o ut  p eri o d.
R ef er e nc e  t h er a p y
R ef er e nc e  is a  pl ac e b o.
St atistic al  
M et h o d ol o g y
D uri n g  t h e p h e n ot y p e  p h as e:  C o m p aris o ns  b et w e e n  t h e a d ult  A D H D  
p ati e nts  c o h orts wit h S C T  a n d  wit h o ut  S C T  i n t er ms of  A D H D  
s y m pt o ms will  b e e x a mi n e  vi a  O n e  W a y  A N O V A  .
Tr e at m e nt  P h as e:  C h a n g es  i n o utc o m e  r ati n gs i n t h e p ati e nts  i n t h e 
tr e at m e nt p h as e  wit h  L D X a n d  pl ac e b o  will b e  m o d el e d  wit h  
l o n git u di n al g e n er aliz e d  esti m ati n g  e q u ati o n  ( G E E) mi x e d  
r e gr essi o n m o d els  usi n g  S T A T A  1 2. 0  [ St at a C or p, 2 0 1 1  # 2 5 8 5 6]  
wit hi n  t h e fr a m e w or k of  t h e g e n er al  li n e ar m o d el  ( G L M).
P a g e 9


[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1
I nt r o d u cti o n
T his  d oc u m e nt  is a  pr ot oc ol  f or a  h u m a n  r es e arc h st u d y. T his  st u d y is t o b e  c o n d uct e d 
i n acc or d a nc e  wit h  U S  g o v er n m e nt  r es e arc h r e g ul ati o ns, a n d  a p plic a bl e  i nt er n ati o n al 
st a n d ar ds of  G o o d  Cli nic al  Pr actic e,  a n d  i nstit uti o n al r es e arc h p olici es  a n d   
pr oc e d ur es.
1. 1
B a c k g r o u n d
S C T  d escri b es  i n di vi d u als w h o  ar e  “ dr e a m y”, “s p ac e y”, sl o w m o vi n g,  h y p o acti v e,  h a v e  
diffic ult y  i niti ati n g t as ks, a n d  oft e n  s e e m u n d er- m oti v at e d  a n d  u n d er- ar o us e d.  I n a  
p o p ul ati o n  s a m pl e of 1, 2 4 9 a d ults wit h a n d  wit h o ut  A D H D,  a n d  wit h  a n d  wit h o ut  S C T,
B ar kl e y  i d e ntifi e d ni n e  c ar di n al s y m pt o ms of  S C T:  1)  pr o n e  t o d a y dr e a mi n g  i nst e a d    
of  c o nc e ntr ati n g; 2)  tr o u bl e st a yi n g al ert / a w a k e  i n b ori n g  sit u ati o ns; 3)  b ei n g  e asil y  
c o nf us e d; 4)  b ei n g  e asil y  b or e d;  5)  f e eli n g s p ac e y /i n a  f o g; 6)  fr e q u e ntl y f e eli n g 
l et h ar gic; 7)  b ei n g  u n d er acti v e / h a vi n g  l ess e n er g y  t h a n ot h ers;  8)  b ei n g  sl o w m o vi n g;
9) n ot  pr oc essi n g  i nf or m ati o n q uic kl y / acc ur at el y  [ 1]. I n di vi d u als w er e  i d e ntifi e d as  
S C T  if t h e y h a d  at  l e ast 5  of  9  s y m pt o ms r at e d oft e n  or  v er y  oft e n  o n  t h e 9-it e m  S C T  
s u bsc al e fr o m t h e B ar kl e y  A d ult  A D H D  R ati n g  Sc al e-I V:  S elf- R e p ort  ( B A A R S-I V; 
h er e aft er  c all e d t h e B ar kl e y  S C T  Sc al e)  [ 2]. T h e  pr e v al e nc e  r at e of  S C T  i n t his s a m pl e 
w as  5. 8 %,  a p pr o xi m at el y  h alf  of  w h o m  h a d  A D H D.  T h es e  r es ults i n dic at e t h at S C T  is 
c o m m o n i n a  l ar g e s u b gr o u p of a d ults  wit h  A D H D,  b ut  is n ot  r estrict e d t o A D H D.
S C T  m a y  r e pr es e nt a  cli nic all y m e a ni n gf ul  c o n diti o n wit h  disti nct  u n d erl yi n g  
p at h o p h ysi ol o g y  a n d  tr e at m e nt r es p o ns e. S e v er al  i n v esti g at ors h a v e  p osit e d  t h e 
e xist e nc e  of  n e ur o bi ol o gic all y  disti nct  s u bt y p es of  A D H D  t h at ar e  diff er e nti all y  
c h ar act eri z e d b y  d eficits  i n e x ec uti v e /i n hi bit or y  c o ntr ol, r e w ar d-r el at e d m oti v ati o n al  
pr oc ess es,  a n d  st at e r e g ul ati o n [ 3- 8]. T his  pr o p os al  t o i n v esti g at e tr e at m e nt r es p o ns e 
of  a d ults  wit h  A D H D  a n d  S C T  is pr o p os e d  i n t h at c o nt e xt. T o  d at e,  t h er e h as  o nl y  b e e n  
o n e  n at ur alistic  tr e at m e nt tri al of  m et h yl p h e ni d at e  ( M P H) i n c hil dr e n wit h  A D H D  a n d  
S C T,  w hic h  f o u n d t h at t h e r es p o ns e f or S C T  w as  l o w er t h a n c or e A D H D  s y m pt o ms [ 9].
P a g e 1 0


[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
H o w e v er,  t h at st u d y w as  d o n e  wit h  M P H.  A  c o ntr oll e d, cli nic al tri al of  L D X  i n a d ult  
A D H D  wit h  a n d  wit h o ut  S C T  is of  critic al i m p ort a nc e f or s e v er al r e as o ns:
1)
S C T  is hi g hl y  c o- m or bi d a n d  i m p airi n g i n a d ult  A D H D  b ut  t h er e h a v e  b e e n  
n o  c o ntr oll e d tr e at m e nt st u di es of  S C T  i n a d ults.
2)
T h e  m a g nit u d e  of r es p o ns e  i n a d ults  wit h  A D H D  a n d  S C T  is n ot  k n o w n,  
b ut  it is pr es u m e d  ( p ossi bl y i nc orr ectl y) fr o m pr eli mi n ar y  p e di atric  d at a  t h at 
it m a y  b e l ess r o b ust [ 9].
3) T h er e  h a v e  b e e n  n o  tr e at m e nt tri als of  a m p h et a mi n es  ( A M P) i n S C T  a n d  
A D H D.
E x a mi ni n g  t h e effic ac y  of  A M P  in  S C T  is i m p ort a nt as  t h e A M P  sti m ul a nt cl ass is m or e  
p ot e nt  t h a n t h e M P H  cl ass t hr o u g h a  d u al  eff ect  o n  a dr e n er gic / d o p a mi n er gic  
p at h w a ys,  w hic h  m a y  b e i m p ort a nt f or eff ects  o n  S C T.
1. 2
I n v e sti g ati o n al  A g e nt
V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  m a n uf act ur e d  b y  S h ir e, is a  D E A  cl ass t w o, 
s y m p at h o mi m etic a mi n e.  Its i n dic ati o ns ar e  f or tr e at m e nt of  att e nti o n- d eficit  
h y p er acti vit y  dis or d er.  T h e  i niti al a d ult  d os a g e  is 3 0 m g  wit h  all o w e d  a dj ust m e nts  i n 
i ncr e m e nts of  1 0 m g  or  2 0 m g  at  w e e kl y  i nt er v als. T h e  m a xi m u m  d os a g e  is 7 0 m g / d a y.  
P e di atric  d os a g e  will  n ot  b e  disc uss e d  as  w e  will  o nl y  r ecr uit a d ults  f or t his st u d y.
V y v a ns e  is s u p pli e d i n 2 0 m g,  3 0 m g,  4 0 m g,  5 0 m g,  6 0 m g,  a n d  7 0 m g  c a ps ul es.
D r u g  i nt e r a cti o n s wit h  V y v a n s e  ( Li s d e x a mf et a mi n e Di m e s yl at e )
Uri n ar y  aci dif yi n g  a g e nts  ( e. g., asc or bic  aci d)  i ncr e as e uri n ar y  e xcr eti o n  a n d  
d ecr e as e  t h e T 1 / 2 of  t h e a m p h et a mi n e,  w hil e  uri n ar y  al k ali nizi n g  a g e nts  ( e. g., 
s o di u m bic ar b o n at e)  d ecr e as e  uri n ar y e xcr eti o n  a n d  e xt e n d  t h e T 1 / 2  of  t h e 
a m p h et a mi n e;  a dj ust  d os e  acc or di n gl y.  T h er e  c a n b e  p ossi bl e  c o ntr ai n dic ati o ns wit h  
V y v a ns e  if us e d  wit h  a n  M A OI  or  us e d  wit hi n  1 4  d a ys  of  t h e l ast M A OI  d os a g e.
P a g e 1 1


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
P r e g n a n c y  wit h  V y v a n s e  ( Li s d e x a mf et a mi n e Di m e s yl at e)
V y v a ns e  is a  C at e g or y  C  a n d  is n ot  f or us e  w hil e  pr e g n a nt  or  n ursi n g.  T h er e  ar e  n o  
a d e q u at e  a n d  w ell-c o ntr oll e d st u di es  wit h  V y v a ns e  i n pr e g n a nt  w o m e n.  V y v a ns e  is a n  
a m p h et a mi n e  a n d  its s y m p at h o mi m etic eff ects  o n  pl ac e nt al  p erf usi o n  a n d  f et al bl o o d  fl o w 
ar e  u n k n o w n.  A d v ers e  pr e g n a nc y  o utc o m es,  i ncl u di n g pr e m at ur e  d eli v er y  a n d  l o w birt h  
w ei g ht  h a v e  b e e n  s e e n i n i nf a nts b or n  t o m ot h ers  d e p e n d e nt  o n  a m p h et a mi n es. A ni m al  
r e pr o d ucti o n st u di es p erf or m e d  wit h  lis d e x a mf et a mi n e di m es yl at e  s h o w e d n o  eff ects  o n  
e m br y of et al  m or p h ol o gic al  d e v el o p m e nt  a n d  s ur vi v al. L o n g-t er m  n e ur oc h e mic al  a n d  
b e h a vi or al  eff ects h a v e  b e e n  s e e n i n a ni m al  d e v el o p m e nt al  st u di es usi n g  cli nic all y r el e v a nt 
d os es  of  a m p h et a mi n e  ( d- or  d,l-).  V y v a ns e  s h o ul d b e  us e d  d uri n g  pr e g n a nc y  o nl y  if t h e 
p ot e nti al  b e n efit  j ustifi es t h e p ot e nti al  ris k t o t h e f et us [ 2 8].
V y v a n s e  ( Li s d e x a mf et a mi n e Di m e s yl at e)  m e c h a ni s m  of  a cti o n
S y m p at h o mi m etic  a mi n e;  C N S  sti m ul a nt. Pr o d uct  of d e xtr o a m p h et a mi n e.  Bl oc ks  t h e 
r e u pt a k e of  n or e pi n e p hri n e  a n d  d o p a mi n e  i nt o t h e pr es y n a ptic  n e ur o n  a n d  
i ncr e as es t h e r el e as es of  t h es e m o n o a mi n es  i nt o t h e e xtr a n e ur o n al  s p ac e.
V y v a n s e  ( Li s d e x a mf et a mi n e Di m e s yl at e)  P h a r m a c o ki n eti c s
A bs or pti o n:  R a pi d;  T m a x = 1  hr  ( Lis d e x a mf et a mi n e), 3. 5  hrs  ( D e xtr o a m p h et a mi n e). 
Distri b uti o n:  F o u n d  i n br e ast  mil k.  M et a b olis m:  H y dr ol ysis  b y  R B C;  
D e xtr o a m p h et a mi n e  ( acti v e m et a b olit e).  Eli mi n ati o n:  Uri n e  ( 9 6 %; 4 2 %  
a m p h et a mi n e,  2 %  u nc h a n g e d),  f ec es ( 0. 3 %); T 1 / 2 = < 1  hr.  ( w w w. nl m. ni h. g o v).
1. 3
P r e cli ni c al  D at a
V y v a ns e  is a p pr o v e d  b y  t h e F o o d  a n d  Dr u g  A d mi nistr ati o n  ( FD A)  f or t h e tr e at m e nt 
of  A D H D  i n a d ults  a n d  c hil dr e n. S C T  d escri b es  i n di vi d u als w h o  ar e  “ dr e a m y,” 
“s p ac e y,” sl o w m o vi n g,  h y p o acti v e,  h a v e  diffic ult y  i niti ati n g t as ks, a n d  oft e n  s e e m 
u n d er- m oti v at e d  a n d  u n d er- ar o us e d.  T his  st u d y will  d et er mi n e  si mil ariti es a n d  
diff er e nc es  b et w e e n  a d ults  wit h  A D H D  wit h  S C T  a n d  a d ults  wit h  A D H D  wit h o ut S C T.  
T his  i m p ort a nt st u d y will  i n v esti g at e t h e tr e at m e nt r es p o ns e of A d ults  wit h  A D H D
P a g e 1 2


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
a n d  S C T  usi n g  V y v a ns e  v ers es  Pl ac e b o  (s u g ar pill).  I nf or m ati o n r e g ar di n g t h e 
cli nic al pr es e nt ati o n  of  a d ults  wit h  A D H D  (t h os e wit h  a n d  wit h o ut  S C T)  will  
est a blis h t h e  p ot e nti al  utilit y  of  L D X  i n t h e p o p ul ati o n  of  a d ults  wit h  A D H D  a n d  S C T.  
As  s uc h, t his st u d y will a d dr ess  i m p ort a nt g a ps  i n t h e e xisti n g  tr e at m e nt lit er at ur e.
1. 4
Cli ni c al  D at a  t o D at e
T o  d at e,  t h er e h as  o nl y b e e n  o n e  n at ur alistic  tr e at m e nt tri al of  m et h yl p h e ni d at e  
( M P H) i n c hil dr e n wit h  A D H D  a n d  S C T , w hic h  f o u n d t h at t h e r es p o ns e f or S C T  w as  
l o w er t h a n c or e A D H D  s y m pt o ms [ 9]. H o w e v er, t h at  st u d y w as  d o n e  wit h  M P H.
A  c o ntr oll e d, cli nic al tri al of  L D X  i n a d ult  A D H D  wit h  a n d wit h o ut  S C T  is of  critic al 
i m p ort a nc e f or s e v er al r e as o ns:
1) S C T  is hi g hl y  c o- m or bi d a n d  i m p airi n g i n a d ult  A D H D  b ut  t h er e h a v e  b e e n  
n o  c o ntr oll e d tr e at m e nt st u di es of  S C T  i n a d ults.
2) T h e  m a g nit u d e  of r es p o ns e i n a d ults  wit h  A D H D  a n d  S C T  is n ot  k n o w n,  b ut  
it is pr es u m e d  ( p ossi bl y i nc orr ectl y) fr o m pr eli mi n ar y  p e di atric  d at a  t h at it 
m a y  b e  l ess r o b ust [ 9].
3) T h er e  h a v e  b e e n  n o  tr e at m e nt tri als of  a m p h et a mi n es  ( A M P) i n S C T  a n d  
A D H D.
E x a mi ni n g  t h e effic ac y  of  A M P  in  S C T  is i m p ort a nt as  t h e A M P  sti m ul a nt cl ass is m or e  
p ot e nt  t h a n t h e M P H  cl ass t hr o u g h a  d u al  eff ect  o n  a dr e n er gic / d o p a mi n er gic  
p at h w a ys,  w hic h  m a y  b e i m p ort a nt f or eff ects  o n  S C T.
1. 5
D o s e  R ati o n al e
F D A  d at a  o n  a d ult  s h ort t er m d osi n g  i nf or m ati o n fr o m cli nic al tri als s h o w t h at d os es  
of  V y v a ns e  ar e  3 0  m g,  5 0 m g  or  7 0 m g.  T h e  p ati e nts  w er e  i niti at e d o n  t h es e d os es    
a n d  t h e n t h e y w er e  titr at e d u p b y  2 0 m g  wit h  a  m a xi m u m  d os e  of 7 0 m g.
P a g e 1 3


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1. 6
R e s e a r c h  Ri s k s  &  B e n efit s
1. 6. 1
Ri s k  of  St u d y D r u g
St u d y  dr u g  ris ks wit h  V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  ar e  d ecr e as e d  
a p p etit e,  i ns o m ni a, u p p er a b d o mi n al  p ai n, irrit a bilit y,  n a us e a  a n d  v o miti n g,  w ei g ht  
d ecr e as e d,  dr y  m o ut h,  di zzi n ess,  aff ect l a bilit y,  r as h, di arr h e a,  a n xi et y,  a n or e xi a,  
jitt er y f e eli n g, a n d a git ati o n.  P ati e nts  will b e  t ol d t o t a k e m e dic ati o n  o nc e  d ail y  i n 
t h e m or ni n g  a n d  r e p ort if t h e y h a v e  a n y  of  t h es e eff ects  at  e ac h  visit  [ 1 0].
W ar ni n gs  a n d  Pr ec a uti o ns  wit h  V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  ar e  
s u d d e n d e at h,  str o k e, a n d  m y oc ar di al  i nf arcti o n ( MI) r e p ort e d i n a d ults.  S u d d e n  
d e at h  r e p ort e d i n c hil dr e n a n d  a d ol esc e nts  wit h  str uct ur al c ar di ac a b n or m aliti es  
a n d  ot h er  s eri o us h e art  pr o bl e ms  [ 1 0]. P ati e nts  will  h a v e  a n  el ectr oc ar di o gr a p h  
( E K G) pri or  t o i n d ucti o n o n  V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e).  S u bj ects  will  
b e  m o nit or e d  w e e kl y  f or h y p ert e nsi o n,  t ac h yc ar di a a n d  a n y  c ar di ac a b n or m aliti es.  
P e o pl e  wit h  h e art  a b n or m aliti es  will  n ot  b e  tr e at e d wit h  a m p h et a mi n es. T h es e  
s eri o us b ut  u nc o m m o n  si d e eff ects  w er e  r e p ort e d b y  p e o pl e  w h o  t o o k V y v a ns e.
T h e  f oll o wi n g c ar di o v asc ul ar  si d e eff ects  (i n v ol vi n g t h e h e art  a n d / or  bl o o d  v ess els)  
h a v e  b e e n  r e p ort e d wit h  t h e us e  of  a m p h et a mi n es:

S u d d e n  d e at h

C ar di o m y o p at h y  ( e nl ar g e m e nt of  t h e h e art  or  m uscl e  w e a k n ess)

M y oc ar di al  i nf arcti o n ( h e art att ac k)

I ncr e as e d bl o o d  pr ess ur e

T ac h yc ar di a  (r a pi d h e art  r at e)

P al pit ati o ns  (f orc ef ul, s o m eti m es irr e g ul ar h e art b e ats)
V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  m a y  e x ac er b at e  s y m pt o ms of  b e h a vi or  
dist ur b a nc e  a n d  t h o u g ht dis or d er  i n p ati e nts  wit h  a  pr e e xisti n g  ps yc h otic  dis or d er.  
V y v a ns e  m a y  i n d uc e a  mi x e d / m a nic  e pis o d e  i n p ati e nts wit h  bi p ol ar  dis or d er.
P ati e nts  will  b e  scr e e n e d f or a n y  pr e e xisti n g  A xis  1  d i a g n osis, w hic h  w o ul d  e xcl u d e  
t h e m fr o m t h e st u d y.
P a g e 1 4


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
T h e  f oll o wi n g u nc o m m o n  c e ntr al n er v o us  s yst e m si d e eff ects  i n v ol vi n g t h e br ai n  
a n d / or  s pi n al c or d h a v e  b e e n  r e p ort e d wit h t h e us e  of  a m p h et a mi n e:  str o k e, 
ps yc h otic  e pis o d es,  m a ni a,  e u p h ori a,  d e pr essi o n,  d ys p h ori a,  o v ersti m ul ati o n,  
a g gr essi v e  b e h a vi or,  h ostilit y,  s eiz ur es, tr e m or, d ys ki n esi a,  e x ac er b ati o n  of  p h o nic  
tics i ncl u di n g T o ur ett e’s  s y n dr o m e or  m ot or  tics, bl urr y  visi o n,  dizzi n ess,  
r estl ess n ess, a n d  h e a d ac h e.  If d uri n g  t h e c o urs e of  t h e st u d y p ati e nt  d e v el o ps  a n y  of  
t h es e si d e eff ects  i ncl u di n g c h a n g es i n m o o d,  t h e st u d y d oct or  will  disc o nti n u e  
p ati e nt  fr o m t h e st u d y a n d  r ef er t h e p ati e nt  t o r e g ul ar tr e at m e nt.
V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  is ass oci at e d  wit h  d ecr e as e d  w ei g ht  a n d  
gr o wt h  i n p e di atric  p ati e nts  w hic h will  n ot  b e  st u di e d i n t his cli nic al tri al. T h er e  ar e  
als o  t h es e u nc o m m o n  g astr oi nt esti n al  si d e eff ects:  di arr h e a,  c o nsti p ati o n, urtic ari a,  
s ki n r as h es, u n pl e as a nt  t ast e, a n d  ot h er all er gic  r e acti o ns.
V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  is als o  ass oci at e d  wit h  p eri p h er al  
v asc ul o p at h y,  i ncl u di n g R a y n a u d's  p h e n o m e n o n,  w hic h  g e n er all y  i m pr o v es aft er  
d os e  r e d ucti o n or  disc o nti n u ati o n.  O bs er v e  c ar ef ull y f or di git al  c h a n g es d uri n g  
tr e at m e nt.
S o m eti m es  p e o pl e  h a v e  all er gic  r e acti o ns t o dr u gs.  All er gic  r eacti o ns  c a n b e  mil d  or  s e v er e, 
b ut  t h e y s h o ul d al w a ys  b e  t a k e n s eri o usl y. I n r ar e c as es, s e v er e all er gic  r e acti o ns c a n b e  
lif e-t hr e at e ni n g.
S o m e  t hi n gs t h at h a p p e n  d uri n g  a n  all er gic  r e acti o n ar e:

A  r as h

H a vi n g  a  h ar d  ti m e br e at hi n g

W h e e zi n g  w h e n  y o u  br e at h e

S u d d e n  dr o p  i n bl o o d  pr ess ur e

S w elli n g  ar o u n d  t h e m o ut h,  t hr o at, or  e y es

F ast  p uls e

S w e ati n g
P a g e 1 5


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1. 6. 2
Ot h e r  Ri s k s of  St u d y P a rti ci p ati o n
T h er e  ar e  ot h er  p ot e nti al  ris ks ass oci at e d  wit h  p artici p ati n g  i n t his st u d y. P ati e nts  
will  b e  m a d e  a w ar e  of t h es e ris ks. T h er e is  a  mi ni m al  ris k w h e n  o bt ai ni n g  bl o o d  
s a m pl es, w hic h i ncl u d e sli g ht br uisi n g,  s w elli n g, p ai n,  bl o o d  cl ots, a n d  a  s m all ris k of  
i nf ecti o n or  a  t e m p or ar y f e eli n g of  f ai nt n ess. O nl y  e x p eri e nc e d  tr ai n e d st aff will  
p erf or m  p hl e b ot o m y  o n  t h es e p ati e nts.  A mi ni m al  ris k is ass oci at e d wit h  a n  E K G,  
w hic h  i ncl u d e a n  i niti al f e eli n g of  c ol d n ess w h e n  t h e t est m at eri al  t o uc h es y o ur s ki n  
a n d  a  l oc ali z e d r as h or  s ki n irrit ati o n fr o m t h e t est m at eri al.
T h er e  is t h e ris k ass oci at e d  wit h  t a ki n g a  pl ac e b o,  w hic h is  si mil ar t o n ot  t a ki n g 
m e dic ati o n  f or A D H D.  W h e n  p ati e nts  t a k e pl ac e b o  d uri n g  t h e st u d y, it is p ossi bl e  
t h at t h eir A D H D  s y m pt o ms m a y  r et ur n or  g et  w ors e.  T h e  st u d y d oct or  a n d  t h e st u d y 
st aff will  m o nit or  t h es e A D H D  s y m pt o ms w hil e  t h e p ati e nt  is t a ki n g t h e pl ac e b o.
T h er e  is a  ris k if p ati e nts  st o p t h eir r e g ul ar m e dic ati o n  t o b e  i n t h e st u d y; t h eir 
A D H D  s y m pt o ms m a y  r et ur n or  g et  w ors e.  It w o ul d b e  vit al  t o i nf or m t h e p ati e nts  t o 
t ell t h e st u d y d oct or  or  st u d y st aff ri g ht a w a y  if t h e y h a v e  a n y  pr o bl e ms.
T h e  ris k ass oci at e d  wit h  st o p pi n g c urr e nt A D H D  m e dic ati o ns  b e f or e st arti n g t h e 
st u d y i ncl u d e: di zzi n ess,  n a us e a,  h e a d ac h e,  a b n or m al  s e ns ati o ns i n ar ms  a n d  l e gs, 
f ati g u e, v o miti n g,  irrit a bilit y, sl e e pl ess n ess, di arr h e a,  a n xi et y,  f ai nti n g, e xc essi v e  
s w e ati n g. T h es e  si d e- eff ects wit h  si mil ar dr u gs  w er e  t e m p or ar y a n d  us u all y  
r es ol v e d b y  t h e ms el v es.
T h er e  is a  p o ssi bl e ris k of  l oss of  c o nfi d e nti alit y r el at e d t o uri n e  scr e e ns a n d  cli nic al 
d at a  o bt ai n e d  d uri n g  t his st u d y. As  a  g u ar d a g ai nst  t h e l oss of  c o nfi d e nti alit y, all  
i nf or m ati o n will  b e  st or e d i n l oc k e d fil es w hic h  c a n b e  acc ess e d  o nl y  b y  m e m b ers  of 
t h e r es e arc h st aff f or t his pr oj ect.
P a g e 1 6


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1. 6. 3
P ot e nti al  b e n efit s
T his  r es e arc h st u d y i ncl u d es pr oc e d ur es t h at m a y  c ha n g e  t h e tr e at m e nt p ati e nts  wit h  
A D H D  w o ul d  ot h er wis e r ec ei v e.  W e  h o p e  k n o wl e d g e  g ai n e d  will  b e  of  b e n efit  t o t h e 
p ati e nts.  W hil e t h er e  m a y  n ot  b e  a  dir ect b e n efit  t o t h e p ati e nts,  it is h o p e d t h at  t h e 
k n o wl e d g e  g ai n e d  will b e n efit  ot h ers  i n t h e f ut ur e.
2
St u d y  O bj e cti v e s
Pri m ar y  O bj ecti v e:  T h e  pri m ar y  o bj ecti v e  is t o e x a mi n e  c h a n g es i n r ati n gs of  A D H D  
s y m pt o ms a n d  S C T.  T h e  pri m ar y  m e as ur e  of  A D H D  s y m pt o ms will  b e  t h e t ot al sc or e o n  
t h e A D H D  R ati n g  Sc al e  ( A D H D- R S) wit h  pr o m pts  [ 1 6]. T h e  pri m ar y  m e as ur e  of  S C T  will  
b e  t h e B ar kl e y  S C T  Sc al e.
S ec o n d ar y  O bj ecti v es:
1)
E x a mi n e  c h a n g es i n t h e B RI E F- A M et ac o g niti o n  I n d e x a n d M oti v ati o n 
S u bsc al es  as  t h es e s u bsc al es ar e  m or e  cl os el y r el at e d t o m e as ur es  of  ar o us al  
a n d  m oti v ati o n  t h a n ot h er  s u bsc al es of  t h e B RI E F- A.
2)
E x a mi n e  c h a n g es i n r ati n gs of f u ncti o n al i m p air m e nt vi a t h e B  B ar kl e y  
F u ncti o n al  I m p air m e nt Sc al e ( B FI S).
3)
E x a mi n e  c h a n g es i n a  b att er y  of  n e ur o ps yc h ol o gic al  t ests of ar o us al  a n d  
al erti n g,  i ncl u di n g:
i.
T h e  C a m bri d g e  N e ur o ps yc h ol o gic al  T esti n g  A ut o m at e d  B att er y  
( C A N T A B) A D H D  b att er y:  A  v ali d at e d b att er y  of  4  t ests w hic h  ass ess  
m ot or  s p e e d ( M ot or C o ntr ol  T as k),  s p ati al w or ki n g  m e m or y  ( S p ati al 
W or ki n g  M e m or y),  r es p o ns e i n hi biti o n ( St o p Si g n al  T as k),  a n d  
s ust ai n e d att e nti o n  ( R a pi d Vis u al  I nf or m ati o n Pr oc essi n g)  [ 1 7]. I n 
a d diti o n, w e h a v e i ncl u d e d t h e Att e nti o n S witc hi n g T as k ( A S T), a n us ef ul t est 
i n d efi ni n g t h e c o g niti v e p h e n ot y p e i n i n di vi d u als wit h A D H D + hi g h I Q. 
M e as ur es  of  r e acti o n ti m e a n d  r e acti o n ti m e v ari a bilit y  will  b e 
P a g e 1 7


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
e x a mi n e d.  
ii.
T h e  W ec hsl er  A d ult  I nt elli g e nc e Sc al e-I V  ( W AI S-I V): C o di n g  a n d  
S y m b ol  S e arc h  s u bt ests will  b e  us e d  t o e v al u at e  pr oc essi n g  s p e e d 
[ 1 8].
4) E x a mi n e  p ot e nti al  diff er e nc es  i n n at ur e a n d  s e v erit y of  A D H D  s y m pt o ms (t ot al, 
i n att e nti v e, a n d  h y p er acti v e-i m p ulsi v e),  s y m pt o ms of  e x ec uti v e  f u ncti o n 
( B RI E F G E C,  m et ac o g niti o n,  b e h a vi or al  r e g ul ati o n sc al es a n d s u bsc al es: I n hi bit, 
S hift, E m oti o n al C o ntr ol, I niti at e, W or ki n g M e m or y, Pl a n / Or g a ni z e, 
Or g a ni z ati o n of M at eri als, M o nit or), n e ur o ps yc h ol o gic al t est p erf or m a nc e o n 
t h e C A N T A B a n d W AI S s u bt ests list e d a b o v e, a n d i m p air m e nt ( B ar kl e y 
F u ncti o n al I m p air m e nt Sc al e ( B FI S)) [ 2 7]
5) T h e O n- T o p sc al e will b e us e d o n tr e at m e nt o utc o m e i n a d ult A D H D t o m e as ur e 
e x ec uti v e f u ncti o ns  i n d ail y  lif e.[ 2 9][ 3 0]
3
St u d y  D e si g n
3. 1
G e n e r al  D e si g n
1)
T ot al  n u m b er of  s u bj ects / T ot al s a m pl e  si z e: A p pr o xi m at el y  1 2 0  p ati e nts  wit h  
A D H D  ( wit h t h e fi n al n u m b er  of  s u bj ects d e p e n di n g  o n  t h e pr o p orti o n  of  A D H D  
s u bj ects w h o  h a v e  S C T;  w e  h a v e  b as e d  o ur  pr oj ecti o ns  o n  a n  esti m at e d  5 0 %  
pr e v al e nc e)  i n t h e p h e n ot y p e  p h as e  (scr e e ni n g visit);  5 0  a d ults  wit h  A D H D  a n d  
S C T +  will  e nt er  t h e tr e at m e nt p h as e  wit h  L D X  a n d pl ac e b o.  W e  will  a n al y z e  d at a  
fr o m all  s u bj ects w h o t a k e  at  l e ast o n e  d os e  of  m e dic ati o n  i n b ot h bl oc ks.  Usi n g  a  
2 0 %  dr o p- o ut r at e  t o occ ur t hr o u g h o ut  t h e tri al, w e  esti m at e  t h at a p pr o xi m at el y  5 0  
s u bj ects will e nr oll i n  t h e tri al; 4 6 p ati e nts will c o m pl et e t h e  first p h as e of 
tr e at m e nt, 4 4  p ati e nts  will c o m pl et e t h e  i nt er v e ni n g pl ac e b o  w as h o ut,  a n d  4 0  
p ati e nts  will c o m pl et e  e ac h  tr e at m e nt p h as e.
2)
J ustific ati o n f or s a m pl e si z e: W e will  e nr oll  a  s uffici e nt n u m b er  of  s u bj ects t o r ecr uit 
8 0  p ati e nts  wit h  A D H D  a n d  S C T  t o e nt er  t h e tr e at m e nt st u d y. T h e  5 0 %  pr e v al e nc e  of  
S C T  i n a d ult  A D H D  h as  b e e n  est a blis h e d  i n c o m m u nit y s a m pl es [ 1, 2].  P o w er  f or t his 
st u d y w as  c alc ul at e d usi n g  P A S S  [ 2 2] b as e d  o n  t h e pri m ar y  o utc o m e,  i. e.   c h a n g e 
b et w e e n b as eli n e  a n d w e e k  4  of  tr e at m e nt o n  t h e B ar kl e y S C T sc al e.  Pr e vi o us  
st u di es s u g g est t h at t h e u p p er  b o u n d  of  t h e eff ect  siz e f or t h e c o m p aris o n of  A D H D  
P a g e 1 8


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
m e dic ati o ns  vs.  pl ac e b o  f or A D H D  s ym pt o ms  v ari es b et w e e n  1. 2  a n d  1. 5  st a n d ar d 
d e vi ati o ns.  Usi n g  a  c o ns er v ati v e esti m at e  of  eff ect  t h at is h alf  as  r o b ust f or S C T  as  
A D H D  w e  b as e d  o n  o ur  c alc ul ati o ns o n  a  0. 6  E S  f or S C T  s y m pt o ms. T h e  pri m ar y  
c o m p aris o n will  b e  a  r e d ucti o n i n S C T  s y m pt o ms o n  L D X  vs.  pl ac e b o.  Wit h  4 5  
e v al u a bl e p ati e nts  wit h  S C T  w e  will  h a v e  8 0 %  p o w er  t o d et ect  a n eff ect  siz e   ( E S) of  
0. 6  usi n g  a  t w o-si d e d t est wit h  a  t y p e I err or  of  0. 0 5.
St u d y  P h a s e s
R ecr uit m e nt  a n d  S el ecti o n  of  S C T  c as es ( P h e n ot y p e p h as e)
W e  pl a n  t o r ecr uit 1 2 0  a d ults  ( 2 0 % scr e e n f ail r at e), t o e v al u at e  at  t he  scr e e ni n g visit  
a p pr o xi m at el y  1 0 0  a d ults  wit h  A D H D  at  t w o sit es ( N Y U a n d  M o u nt  Si n ai)  t o i d e ntif y 
5 0  S C T +  a n d  5 0  S C T -. T h es e p ati e nts  will  b e  e v al u at e d  wit h  cli nic al m e as ur es  of  S C T  
( B ar kl e y S C T  Sc al e),  A D H D  ( A D H D- R S wit h  pr o m pts),  e x ec uti v e  f u ncti o n ( B RI E F- A), 
ass ess m e nt  of  ot h er  ps yc hi atric  dis or d ers  ( M.I. N.I.), gl o b al  i m p air m e nt ( C GI), 
f u ncti o n al i m p air m e nt ( B ar kl e y F u ncti o n al I m p air m e nt Sc al e  ( B FI S)), s uici d alit y ( C- 
S S R S),  a n d  n e ur o ps yc h ol o gic al  f u ncti o n ( n e ur o ps yc h ol o gic al b att er y).  O nl y  p ati e nts  
i n t h e S C T +  c o h ort will  e nt er  t h e tr e at m e nt p h as e  of  t h e pr ot oc ol.
L D X Tr e at m e nt P h as e
W e ar e pr o p osi n g a 2-sit e ( N Y U a n d M o u nt Si n ai) st u d y of L D X i n 5 0 a d ults wit h 
A D H D + S C T. T h e st u d y will b e a d o u bl e- bli n d, 1 0- w e e k, cr oss- o v er tr e at m e nt tri al of 
L D X ( 4 w e e ks; 3 0 – 7 0 m g / d a y) vs. pl ac e b o ( 4 w e e ks) wit h a n i nt er v e ni n g si n gl e-
bli n d pl ac e b o w as h o ut p eri o d ( 2 w e e ks). D uri n g t h e L D X tr e at m e nt e p oc h, L D X 
tr e at m e nt will b e i niti at e d at a d os e of 3 0 m g / d a y at Visit 2 a n d c a n b e titr at e d u p (i n 
t h e j u d g m e nt of t h e i n v esti g at or) i n i ncr e m e nts of 2 0 m g, b as e d u p o n cli nic al 
r es p o ns e a n d t ol er a bilit y, t o 5 0 m g / d a y at Visit 1 a n d 7 0 m g / d a y at Visit 3. S u bj ects 
r ec ei vi n g d ail y d os es of 5 0 m g or 7 0 m g of L D X will b e all o w e d t o d o w n titr at e o n e 
d os a g e st e p of 2 0 m g d uri n g Visits 3- 5 if (i n t h e j u d g m e nt of t h e i n v esti g at or) t h e y 
ar e h a vi n g iss u es i n t ol er a bilit y. T h e hi g h est eff ecti v e d os e of L D X will t h e n b e 
m ai nt ai n e d u ntil Visit 6. P ati e nts will b e s e e n w e e kl y t hr o u g h o ut t h e tri al e xc e pt 
d uri n g pl ac e b o w as h o ut.  T h e s a m e sc h e d ul e will occ ur d uri n g P h as e 2 of t h e st u d y.  
P a g e 1 9


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
D uri n g t h e P h as e 2 L D X tr e at m e nt e p oc h, L D X tr e at m e nt will b e i niti at e d at a d os e of 
3 0 m g / d a y at Visit 7 a n d c a n b e titr at e d u p (i n t h e j u d g m e nt of t h e i n v esti g at or) i n 
i ncr e m e nts of 2 0 m g, b as e d u p o n cli nic al r es p o ns e a n d t ol er a bilit y, t o 5 0 m g / d a y at 
Visit 1 a n d 7 0 m g / d a y at Visit 8.  T h e titr ati o n pr oc e d ur e will f oll o w t h at of p h as e 1.
3. 2
P ri m a r y  St u d y  E n d p oi nt s
T h e  pri m ar y  st u d y e n d p oi nt  is t o e x a mi n e  t h e effic ac y  of  lis d e x a mf et a mi n e 
di m es yl at e  ( L D X) v ers us  pl ac e b o  o n  s y m pt o ms of  sl u g gis h c o g niti v e t e m p o ( S C T) i n 
a d ults  wit h  A D H D  a n d  S C T.
3. 3
S e c o n d a r y St u d y  E n d p oi nt s
T h e  s ec o n d ar y st u d y e n d p oi nts  ar e  t o d efi n e  t h e S C T  p h e n ot y p e  a n d  d et er mi n e  
si mil ariti es a n d  diff er e nc es b et w e e n  a d ults  wit h  A D H D  wit h  a n d  wit h o ut  S C T o n  S C T  
s y m pt o ms, e x ec uti v e  f u ncti o n s y m pt o ms, n at ur e  a n d  s e v erit y of  A D H D  s y m pt o ms, 
a n d  n e ur o ps yc h ol o gic al  pr ofil e
4
S u bj e ct  S el e cti o n a n d  Wit h d r a w al
4. 1
I n cl u si o n  C rit e ri a
1)
M al e or f e m al e b et w e e n t h e a g es of 1 8- 6 0 of all r ac es a n d et h nicit y. 
2)
M e ets D S M-I V- T R  crit eri a f or a pri m ar y di a g n osis of i n att e nti v e or c o m bi n e d t y p e 
A D H D as di a g n os e d vi a t h e A d ult A D H D Cli nici a n Di a g n ostic Sc al e v ersi o n 1. 2 ( A C D S 
v 1. 2) [ 1 0].
3)
If S C T + gr o u p, ≥ 5 it e ms o n t h e B ar kl e y S C T Sc al e m ust b e r at e d 3 (“ oft e n”) or 4 
(“ v er y oft e n”) a n d t ot al S C T s y m pt o m sc or e ≥ 2 6; m ust h a v e a T-sc or e ≥ 6 5 o n t h e 
M et ac o g niti o n I n d e x S u bsc al e of t h e B e h a vi or R ati n g I n v e nt or y of E x ec uti v e 
F u ncti o n - A d ult V ersi o n ( B RI E F- A) [ 1 1].
4)
If S C T + gr o u p, I m p air m e nt: m ust h a v e a t ot al sc or e > 9 5t h p erc e ntil e o n t h e B ar kl e y 
F u ncti o n al I m p air m e nt R ati n g Scr e e n ( B ar kl e y F u ncti o n al I m p air m e nt Sc al e ( B FI S) 
[ 1 3].
5 )
If S C T- gr o u p, < 5 it e ms o n t h e B ar kl e y S C T Sc al e m ust b e r at e d 3 (“ oft e n”) or 4 
(“ v er y oft e n”) a n d t ot al S C T s y m pt o m sc or e < 2 6; m ust h a v e a T-sc or e < 6 5 o n t h e 
M et ac o g niti o n I n d e x a n d M oti v ati o n S u bsc al es of t h e B RI E F- A.
P a g e 2 0


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
4. 2
E x cl u si o n  C rit e ri a
1)
M e ets  D S M-I V- T R  crit eri a f or a  pri m ar y  di a g n osis  of  h y p er acti v e-i m p ulsi v e  t y p e 
A D H D  as  di a g n os e d  vi a  t h e A C D S  v 1. 2.
2)
A n y  ot h er  c urr e nt ps yc hi atric  dis or d er,  d et er mi n e d  vi a  t h e M.I. N.I ,  w hic h  
r e q uir es p h ar m ac ot h er a p y  tr e at m e nt.
3)
C urr e nt  s uici d al i d e ati o n or  hist or y  of  s uici d e att e m pts,  b as e d  o n  t h e 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)  [ 1 5].
4)
Lif eti m e  hist or y  of  bi p ol ar  dis or d er  or  a n y  ps yc h otic  dis or d er  as  p er  t h e M.I. N.I
5)
Pr e g n a nt,  br e astf e e di n g  or  w o m e n  pl a n ni n g  t o b ec o m e  pr e g n a nt.
6)
P ositi v e  uri n e  dr u g  t o xic ol o g y ar e  e xcl u d e d.
7)
A n y ot h er r e as o n t h at, i n t h e o pi ni o n of t h e i n v esti g at or, pr e v e nts t h e s u bj ect fr o m 
p artici p ati n g i n t h e st u d y or c o m pr o mis e t h e s u bj ect s af et y.
4. 3
S u bj e ct  R e c r uit m e nt  a n d  S c r e e ni n g
W e pl a n t o r ecr uit 1 2 0 a d ults ( 2 0 % scr e e n f ail r at e) t o e v al u at e at t h e scr e e ni n g visit; 
a p pr o xi m at el y 1 0 0 a d ults wit h A D H D at t w o sit es ( N Y U a n d M o u nt Si n ai) t o i d e ntif y 
5 0 S C T + a n d 5 0 S C T-. W e will acc e pt r ef err als fr o m ot h er cli nici a ns pr o vi d e d t h at t h e 
p ati e nts h a v e gi v e n t h eir cli nici a ns p er missi o n t o b e c o nt act e d b y t h e st u d y t e a m or 
t h e cli nici a n h as pr o vi d e d o ur c o nt act i nf or m ati o n t o t h e p ati e nt. W e will a d v ertis e 
wit hi n a n d o utsi d e N e w Y or k L a n g o n e M e dic al C e nt er. T h er e ar e fl y ers, r a di o a n d 
pri nt a d v ertis e m e nt cr e at e d a n d a p pr o v e d f or h el p wit h r ecr uit m e nt.
N e w Y or k U ni v ersit y L a n g o n e M e dic al C e nt er a n d M o u nt Si n ai will s u b mit t o t h eir 
o w n I R Bs. S u bj ects will b e s e e n o nl y at l oc ati o n c o ns e nt e d. M o u nt Si n ai will pr o vi d e 
N Y U wit h t h eir I R B a p pr o v als f or s u b missi o n t o t h e N Y U I R B. B ot h l oc ati o ns will 
h a v e t h eir o w n st aff a n d p h ar m ac y.
P ati e nts  will  b e e v al u at e d wit h  cli nic al m e as ur es  of  S C T  ( B ar kl e y S C T Sc al e),  A D H D  
( A D H D- R S wit h  pr o m pts),  e x ec uti v e  f u ncti o n ( B RI E F- A),  ass ess m e nt  of  ot h er  
ps yc hi atric  dis or d ers  ( M.I. N.I) gl o b al  i m p air m e nt ( C GI), f u ncti o n al i m p air m e nt 
( B FI R S), s uici d alit y ( C- S S R S), a n d  n e ur o ps yc h ol o gic al  f u ncti o n ( n e ur o ps yc h ol o gic al 
b att er y).  O nl y  p ati e nts  i n t h e S C T +  c o h ort will e nt er  t h e tr e at m e nt p h as e of  t h e 
pr ot oc ol.
P a g e 2 1


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
I nt e n d e d a g e  f or t his st u d y will  r e q uir e p artici p a nts  t o b e  wit hi n  1 8  y e ars t o 6 0  y e ars  
of  a g e.  T h er e  is n o  r estricti o n as  t o g e n d er,  r ac e or  et h nic  ori gi n  of  p ati e nts.
W e  will  c o nt act p ati e nts  fr o m cli nici a n r ef err als w h o  h a v e  pr o vi d e d  p er missi o n  t o b e  
c o nt act e d or  p ati e nts  will  c all us  fr o m eit h er  a  cli nici a n r ef err al or  a d v ertis e m e nt.
T h e y  will  b e  as k e d  t o pr o vi d e  v er b al  c o ns e nt t o s e e if t h e y w o ul d  b e  a  p o ssi bl e 
c a n di d at e b y  c o m pl eti n g a  pr e-scr e e ni n g  q u esti o n n air e  o v er  t h e p h o n e.  Aft er  t h e pr e- 
scr e e n, a  5  mi n ut e  g e n er al  q u esti o n n air e  a b o ut  t h eir m e nt al  or  p h ysic al  h e alt h,  t h e y 
will  b e  as k e d  t o c o m e i n t o t h e cli nic at  O n e  P ar k  A v e n u e  f or scr e e ni n g. A n a p plic ati o n 
f or w ai v er  of  d oc u m e nt ati o n  of  c o ns e nt will b e  s u b mitt e d as  c o ns e nt is o bt ai n e d  o v er  
t h e t el e p h o n e a n d  t h e q u esti o n n air e  is mi ni m al  ris k. All  c oll ect e d P HI  fr o m a n y o n e  
w h o  d o es  n ot  p ass  t h e pr e-scr e e ni n g  q u esti o n n air e  or  w h o  d eci d es  n ot  t o p artici p at e 
will b e  i m m e di at el y wit h dr a w n.
At  t h e st u d y sit e, r es e arc h st aff will  h a v e  p ati e nts  r e a d t h e c o ns e nt f or m a n d  o pt  t o 
disc uss  wit h  t h eir pri v at e  d oct or  a n d  f a mil y. W h e n  t h e p ati e nt  is r e a d y, r es e arc h 
st aff will  r e a d a n d  r e vi e w e ac h  p a g e  of  c o ns e nt f or m. T h e  r es e arc h st aff will  as k  if 
t h e p ati e nt  u n d erst a n ds  a n d  all o w  t h e p ati e nt  t o as k  q u esti o ns.  Aft er  t h e p ati e nt 
h as  c o m pl et e d t h e i nf or m c o ns e nt pr oc ess  a n d  h as  gi v e n  c o ns e nt b y  si g ni n g t h e 
c o ns e nt d oc u m e nt scr e e ni n g will  b e gi n.  T h e  p ati e nt is  gi v e n  a  c o p y of  t h e si g n e d 
c o ns e nt f or m. T h e  ori gi n al  c o ns e nt f or m will  b e  fil e d i n t h e p ati e nt’s  s o urc e 
d oc u m e nt ati o n  f or t h e st u d y. T h e  r es e arc h st aff will  d oc u m e nt  t h e i nf or m c o ns e nt 
pr oc ess  a n d  fil e t his wit h  t h e p ati e nt’s  s o urc e d oc u m e nts.
If t h e p ati e nt  d o es  n ot  a gr e e  t o p artici p at e  i n t h e st u d y t h e i nf or m c o ns e nt will  b e  
m ai nt ai n e d;  m ar k e d  ac r oss t h e si g n at ur e “ d ecli n e d” wit h  a  n ot e  t o fil e r e g ar di n g 
circ u mst a nc es of  p ati e nt’s  d ecli n e.  S e e  C o ns e nt Pr oc ess  Att ac h m e nt  [ 7]
4. 4
E a rl y  Wit h d r a w al  of  S u bj e ct s
P ati e nts  c a n wit h dr a w  or  t a k e b ac k  t h eir p er missi o n  t o us e  a n d  s h ar e his / h er  h e alt h  
i nf or m ati o n at a n y  ti m e. W h e n  t h e p ati e nt  wit h dr a ws  t h eir p er missi o n,  t h e y will  n ot  
b e  a bl e  t o t a k e b ac k  i nf or m ati o n t h at h as alr e a d y  b e e n  us e d  or  s h ar e d wit h  ot h ers.
P ati e nts  will  b e  m a d e  a w ar e  a n d  i nstr uct e d o n h o w  t o wit h dr a w  t h eir p er missi o n  b y  
P a g e 2 2


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
s e n di n g a  wr itt e n n otic e  t o t h e pri nci p al  i n v esti g at or f or t h e st u d y n ot e d  o n  p a g e  o n e  
of  t h eir c o ns e nt f or m. If p ati e nt  wit h dr a ws  t h eir p er missi o n,  h e /s h e  will  n ot  b e  a bl e  
t o st a y i n t his st u d y. P ati e nts will  b e  wit h dr a w n  if, i n t h e o pi ni o n  of  t h e st u d y d oct or,  
is n o  l o n g er s af e f or t h e p ati e nt  t o p artici p at e i n t h e st u d y. W e  c a n g et  v er b al  
p er missi o n  t o f oll o w- u p t h e p ati e nt  i n t h e e v e nt  t h e y s uff er a d v ers e e v e nts.  W e  will  
d oc u m e nt  t hr e e att e m pts  t o c o nt act t h e p ati e nt  vi a  p h o n e.  If u n a bl e t o c o nt act will  
s e n d t h e p ati e nt  a  c ertifi e d l ett er. Att ac h m e nt  [ 4]
4. 4. 1    D at a  C oll e c ti o n a n d F oll o w- u p  f o r Wit h d r a w n S u bj e ct s
S u bj ects  will  b e  f oll o w e d u p  aft er  wit h dr a w al  f or a n y  a d v ers e  e v e nts  a n d  c o nc o mit a nt 
m e dic ati o ns  us e d  si nc e l ast i n t h e r es e arc h cli nic. T h er e  will  b e  t hr e e d oc u m e nt e d  
att e m pts  t o c o nt act t h e p ati e nt.  I n a d diti o n  w e  will  s e n d a  c ertifi e d l ett er e x pl ai ni n g  
i m p ort a nt t o c o nt act us  f or a  f oll o w- u p a p p oi nt m e nt.  T h es e  c o nt act m et h o ds  al o n g  
wit h  a n y  i nf or m ati o n if o bt ai n e d  will  b e  a d d e d  t o s o urc e d oc u m e nt ati o n.  S e e  att ac h e d  
l ett er ( Att ac h m e nt 3)
5
St u d y  D r u g
5. 1
D e s c ri pti o n
V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  is m a n uf act ur e d  b y  S h ir e. V y v a ns e  is a  D E A  
cl ass t w o, s y m p at h o mi m etic a mi n e.  Its i n dic ati o ns ar e  f or tr e at m e nt of  att e nti o n-  
d eficit  h y p er acti vit y  dis or d er.  T h e  i niti al a d ult  d os a g e  is 3 0 m g  wit h  all o w e d  
a dj ust m e nts  i n i ncr e m e nts of  1 0 m g  or  2 0 m g  at  w e e kl y  i nt er v als. T h e  m a xi m u m 
d os a g e  is 7 0 m g / d a y. V y v a ns e  is s u p pli e d i n 2 0 m g,  3 0 m g,  4 0 m g,  5 0 m g,  6 0 m g,  a n d  
7 0 m g  c a ps ul es. C o ntr a dicti o ns  wit h  V y v a ns e  ar e  us e  wit h  a n  M A OI  or  us e  wit hi n  1 4  
d a ys  of  t h e l ast M A OI  d os a g e.  V y v a ns e  ( Lis d e x a mf et a mi n e Di m es yl at e)  is a  C at e g or y  
C  a n d  is n ot  f or us e  i n n ursi n g.  [ 2 6]
5. 2
T r e at m e nt  R e gi m e n
M e dic ati o n  will  n ot  b e  dis p e ns e d  u ntil w e e k  1  of  t he  st u d y. T h e n  f or f o ur w e e ks  t h e 
d os e  of  L D X  or Pl ac e b o  will b e  dis p e ns e d  st arti n g at  3 0 m g  u p  t o 7 0  m g  p er  d a y  wit h  
a n  i nt er v e ni n g si n gl e- bli n d pl ac e b o w as h o ut  p eri o d  ( 2 w e e ks).
Bl oc k  O n e:  D uri n g  t h e L D X / e p oc h,  L D X / Pl ac e b o  tr e at m e nt will  b e  i niti at e d at  a  d os e  
of  3 0 m g / d a y  at  Visit  2 a n d  c a n b e  titr at e d u p  (i n t h e j u d g m e nt of  t h e i n v esti g at or) i n 
P a g e 2 3


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
i ncr e m e nts of  2 0 m g,  b as e d  u p o n cli nic al  r es p o ns e a n d  t ol er a bilit y, t o 5 0 m g / d a y at  
Visit  3  a n d  7 0 m g / d a y  at  Visit  4.
S u bj ects  r ec ei vi n g d ail y  d os es  of  5 0 m g  or  7 0 m g  of  L D X / Pl ac e b o  will  b e  all o w e d  t o 
d o w n  titr at e o n e  d os a g e  st e p of  2 0 m g  d uri n g  Visits  3- 5 if  (i n t h e j u d g m e nt of  t h e 
i n v esti g at or) t h e y ar e  h a vi n g  iss u es i n t ol er a bilit y. T h e  hi g h est  eff ecti v e  d os e  of  L D X  
will  t h e n b e m ai nt ai n e d  u ntil Visit 6.
Pl ac e b o  W as h o ut:  At  t his ti m e t h e p ati e nt  ar e  i n t h e w as h o ut pl ac e b o  p h as e f or t w o  
w e e ks.
Bl oc k  T w o: At  t h e e n d  of  t h e Pl ac e b o W as h o ut P h as e,  Visit 7 (w e e k  6),  p artici p a nts  
will b e  i niti at e d at  a  d os e  of  3 0 m g / d a y  a n d  c a n b e  titr at e d u p  st arti n g at Visit 8(i n t h e 
j u d g m e nt of  t h e i n v esti g at or) i n i ncr e m e nts of  2 0 m g,  b as e d  u p o n  cli nic al r es p o ns e 
a n d  t ol er a bilit y.
S u bj ects  r ec ei vi n g d ail y  d os es  of  5 0 m g  or  7 0 m g  of  L D X / Pl ac e b o  will  b e  all o w e d  t o 
d o w n  titr at e o n e  d os a g e  st e p of  2 0 m g  d uri n g  Visits  8- 1 0 if  (i n t h e j u d g m e nt of  t h e 
i n v esti g at or) t h e y ar e  h a vi n g  iss u es i n t ol er a bilit y. T h e  hi g h est  eff ecti v e  d os e  of  L D X  
will  t h e n b e m ai nt ai n e d  u ntil Visit  1 1
5. 3
M et h o d  f o r A s si g ni n g  S u bj e ct s t o  T r e at m e nt  G r o u p s
D u e  t o t h e st u d y b ei n g  d o u bl e bli n d, a n  u n bli n d e d  r es e arc h assist a nt  will  c o n d uct t h e 
bl oc k  r a n d o mi z ati o n of  t h e s u bj ects u n d er  t h e s u p er visi o n of  t h e N Y U     p h ar m ac y.  
T h e  bl oc k  r a n d o mi z ati o n will  c h o os e p ati e nts  t o st art eit h er  t h e V y v a ns e  or  pl ac e b o  
p h as e  f or f o ur w e e ks.  Aft er  t h es e f o ur w e e ks t h er e will b e  a  t w o w e e k  w as h o ut,  t h e n 
a g ai n  V y v a ns e  or  pl ac e b o  p h as e  f or a n ot h er f o ur  w e e ks.  At  t h e e n d  of  t h e st u d y, t h e 
p ati e nts  will  b e  as k e d  s af et y q u esti o n n air es.  T h e  p ati e nt  a n d  t h e r es e arc h st aff will 
n ot  k n o w  w h et h er  t h e p ati e nt  is o n  V y v a ns e  or  pl ac e b o.  I n c as e of  a n  e m er g e nc y,  t h e 
p h ar m ac y  c a n br e a k  t h e bli n d  wit h  p er missi o n  fr o m t h e pri nci p al  i n v esti g at or. W e 
will  k n o w  if t h e p ati e nt  is o n  V y v a ns e  or  pl ac e b o  aft er  t h e bli n d is  br o k e n.
5. 4 
P r e p a r ati o n  a n d  A d mi ni st r ati o n  of  St u d y  D r u g
P a g e 2 4


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
W h e n  a  p ati e nt  is c o ns e nt e d a n d  pri or  t o e nr oll m e nt,  t h e r es e arc h st aff will  s e n d t h e 
i n v esti g ati o n al p h ar m ac y  a  c o p y of  t h e i nf or m e d c o ns e nt. O n  t h e d a y  of  
r a n d o mi z ati o n, t h e r es e arc h st aff will  i nf or m t h e i n v esti g ati o n al p h ar m ac y  of  p ati e nt  
st at us vi a s ec ur e  e- m ail.  T h e  i n v esti g ati o n al p h ar m ac y  will  c o n d uct t h e bl oc k  
r a n d o mi z ati o n as  n ot e d  i n s ecti o n 5. 4.  T h e  st u d y d oct or  will  writ e  a  pr escri pti o n  f or 
t h e p ati e nt  n oti n g  t h at t h e st u d y dr u g  n a m e  is list e d as  V y v a ns e / Pl ac e b o.  T h e  
i n v esti g ati o n al p h ar m acist  will  pr e p ar e  t h e st u d y m e dic ati o n  f or p ati e nt   
dis p e ns ati o n,  b as e d  o n  t h e bl oc k  r a n d o miz ati o n a n d  t h e pr escri pti o n  or d er.  A 
p ati e nt s p ecific l a b el will  b e  g e n er at e d  b y  t h e i n v esti g ati o n al p h ar m ac y  a n d  affi x e d  
t o t h e st u d y dr u g  b ottl e.  T h e  h ar d  c o p y of t h e  pr escri pti o n  will  b e  pr o vi d e d  t o t h e 
i n v esti g ati o n al p h ar m ac y  t o b e  fill e d a n d  dis p e ns e d  b y  t h e r es e arc h p h ar m acist  t o 
t h e p ati e nt.  T h e  c o nt act n u m b er of  t h e N Y U  I n v esti g ati o n al Dr u g  S er vic e  (I D S) is 
( 2 1 2) 2 6 3- 5 0 3 9  a n d  t h e g e n er al  e- m ail  a d dr ess  is: 
i n v esti g ati o n al. p h ar m ac y @ n y u mc. or g
5. 5
S u bj e ct C o m pli a n c e M o nit o ri n g
St u d y  t e a m will ass ess a n d  tr ac k s u bj ect c o m pli a nc e wit h  t h e st u d y tr e at m e nt 
r e gi m e n b y as ki n g  p ati e nt a b o ut  c o m pli a nc e wit h d ail y  d osi n g. P ati e nts  will  b e  
r e mi n d e d w e e kl y  t o t a k e d ail y  d osi n g  at  t h e s a m e ti m e e ac h  m or ni n g.  P ati e nts  will b e  
r e q uir e d t o bri n g b ac k  t h eir pill  b ottl es  at  e ac h  visit.  T h er e  will  b e  a  pill  c o u nt at  e ac h  
visit  c o n d uct e d b y  t h e st u d y c o or di n at or. P ati e nts  w h o ar e  si g nific a ntl y n o n-  
c o m pli a nt will  h a v e  t h eir s af et y ass ess e d  b y  st u d y d oct or  a n d  wit h dr a w n  fr o m t h e 
st u d y.
5. 6
P ri o r  a n d  C o n c o mit a nt  T h e r a p y
A n y  m e dic ati o n  or  n o n- p h ar m ac ol o gic al t h er a p y  t h at is t a k e n b y  or  a d mi nist er e d  t o 
t h e s u bj ect at  a n y  p oi nt  d uri n g  t h e c o urs e of  t h e st u d y m ust  b e  r ec or d e d i n t h e c as e 
r e p ort f or m ( C R F).
P ri o r  M e di c ati o n s  All o w e d / Di s all o w e d  D u ri n g  St u d y
S u bj ects  t a ki n g sti m ul a nt or  n o n-sti m ul a nt  m e dic ati o ns  f or t h e tr e at m e nt of  A D H D  
d uri n g  scr e e ni n g will  b e  w as h e d  o ut  f or a  p eri o d  e q ui v al e nt  t o 5  h alf-li v es  of  t h e 
m e dic ati o n  pri or  t o b as eli n e  e v al u ati o ns.
Di s all o w e d  M e di c ati o n s  d u ri n g St u d y
P a g e 2 5


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
Us e  of  a n y  of  t h e f oll o wi n g m e dic ati o ns  is n ot  p er mitt e d  d uri n g  t h e st u d y;
1) A nti d e pr ess a nt  pr escri pti o n  m e dic ati o n  ( e. g., p ar o x eti n e,  s ertr ali n e, v e nl af a xi n e,  
m o n o a mi n e  o xi d as e  [ M A O] bl oc k er,  tric yclic, etc.)  a n d  St.  J o h n’s W ort.
2) A ntic o n v uls a nt  m e dic ati o ns  ( e. g., p h e n yt oi n,  c ar b a m az e pi n e, l a m otri gi n e, 
v al pr oic  aci d,  etc.)  a n d  a nti ps yc h otic  m e dic ati o n.
3) S e d ati n g  a nti hist a mi n es  ( e. g., d o xil a mi n e  s ucci n at e, di p h e n h y dr a mi n e)  f or us e  i n 
s e d ati o n or  ai di n g  wit h  sl e e p. S u bj ects  r o uti n el y us e  s e d ati n g a nti hist a mi n es  f or 
s e as o n al all er gi es  will  b e  r e q uir e d t o s witc h t o n o n-s e d ati n g  alt er n ati v es  f or t h e 
d ur ati o n  of  t h e st u d y, u nl ess  ot h er wis e  c o ntr ai n dic at e d.
4) Ot h er  m e dic ati o ns  t h at m a y  i nt erf er e wit h  t h e ass ess m e nt  of  c o g niti v e f u ncti o n 
ar e  n ot  p er mitt e d  d uri n g  t h e st u d y.
5. 7
P a c k a gi n g  ( P h a r m a c y)

St u d y  dr u g  a n d  pl ac e b o  is s u p pli e d i n 2 0 m g,  3 0 m g,  4 0 m g,  5 0 m g,  6 0 m g,  a n d  7 0 m g  
c a ps ul es i n b ottl es c o nt ai ni n g  # 9 pills e ac h. T h e  b ottl es  will  b e  l a b el e d wit h P ati e nt’s  
n a m e,  st u d y i d e ntific ati o n n u m b er, St u d y  n a m e  a n d  N Y U  I R B n u m b er,  st u d y dr u g  
n a m e,  st u d y dr u g  d os a g e,  str e n gt h, q u a ntit y,  dir ecti o ns  f or us a g e  a n d  p h ysici a n’s  
n a m e  a n d  c o nt act i nf or m ati o n.

St u d y  dr u g  will  b e s hi p p e d  i n b ul k  #  4 0  b ottl es  at  e ac h  s hi p m e nt.
5. 8
Bli n di n g  of St u d y D r u g
T h e  st u d y dr u g  is d o u bl e  bli n d e d.  T h e  r es e arc h st aff; i ncl u di n g st u d y d oct or  a n d  t h e 
p ati e nt  will  n ot  k n o w  if t h e p ati e nt  is r ec ei vi n g V y v a ns e  or pl ac e b o.  T h e  st u d y p h ar m acist  
will  k n o w  w hic h  st u d y m e dic ati o n  eit h er  V y v a ns e  or  Pl ac e b o  t h e p ati e nt  is t a ki n g a n d  
c a n br e a k  t h e bli n d  i n c as e of  a n  e m er g e nc y.
5. 9
R e c ei vi n g,  St o r a g e,  Di s p e n si n g  a n d  R et u r n
5. 9. 1
R e c ei pt  of  D r u g  S u p pli e s
S hir e  p h ar m ac e utic als  will  s hi p t h e st u d y dr u g  q u a ntit y  f or s uffici e nt f or p ati e nts  t o 
b e  e nr oll e d  a n d  tr e at e d at  N Y U L M C vi a  t h e N Y U  I n v esti g ati o n al Dr u g  S er vic e  (I D S), 
c o nt act n u m b er  ( 2 1 2) 2 6 3- 5 0 3 9.  U p o n r ec ei pt  of  t h e of  t h e st u d y tr e at m e nt 
s u p pli es, a n  i n v e nt or y m ust  b e  p erf or m e d  a n d  a  dr u g  r ec ei pt l o g fill e d o ut  a n d  
si g n e d b y  t h e p ers o n  acc e pti n g  t h e s hi p m e nt. It is i m p ort a nt t h at t h e d esi g n at e d  
P a g e 2 6


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
st u d y st aff c o u nts a n d  v erifi es  t h at t h e s hi p m e nt c o nt ai ns all  t h e it e ms n ot e d  i n t h e 
s hi p m e nt i n v e nt or y. A n y  d a m a g e d  or  u n us a bl e  st u d y dr u g  i n a  gi v e n  s hi p m e nt 
( acti v e dr u g  or  c o m p ar at or) will  b e  d oc u m e nt e d  i n t h e st u d y fil es. T h e  i n v esti g at or 
m ust n otif y  st u d y s p o ns or of  a n y  d a m a g e d  or  u n us a bl e  st u d y tr e at m e nts t h at w er e  
s u p pli e d t o t h e i n v esti g at or’s sit e.
5. 9. 2
St o r a g e
St u d y  m e dic ati o n  will  b e  d is p e ns e d i n a  ti g ht, li g ht-r esist a nt c o nt ai n er as  d efi n e d  i n 
t h e U S P.  T h e  st u d y m e dic ati o n  will  b e  st or e d at  2 5º  C  ( 7 7º F).  E xc ursi o ns  p er mitt e d  
t o 1 5- 3 0º  C  ( 5 9- 8 6º F)
5. 9. 3
Di s p e n si n g  of  St u d y  D r u g
T h e  st u d y d oct or  will  writ e  a  pr escri pti o n  f or t h e p ati e nt  n oti n g  t h at t h e st u d y dr u g  
n a m e  is list e d as  V y v a ns e / Pl ac e b o.  T h e  r es e arc h c o or di n at or will  c all p h ar m acist  t o 
pr e p ar e  t h e st u d y m e dic ati o n.  St u d y  c o or di n at or will  f a x t h e pr escri pti o n  t o t h e 
p h ar m acist,  w h o  will  r a n d o miz e t h e p ati e nt  a n d  gi v e  t h e p ati e nt  a  r a n d o miz ati o n 
n u m b er.  T h e  p a p er  pr escri pti o n  will  b e  t a k e n t o t h e i n v esti g ati o n al p h ar m ac y  b y  
st u d y c o or di n at or t o b e  fill e d a n d  dis p e ns e d  b y  r es e arc h p h ar m acist,  dir ectl y  t o t h e 
p ati e nt.  A n  el ectr o nic  r ec or d of  t h e or d er  will  als o  b e  e nt er e d  i nt o t h e E PI C  s yst e m 
b y  t h e r es e arc h p h ysici a n  a n d  v erifi e d  b y  t h e i n v esti g ati o n al p h ar m acist.  T h e  st u d y 
dr u g  will  b e  pr e p ar e d,  l a b el e d a n d  dis p e ns e d  b y  t h e r es e arc h p h ar m acist  fr o m t h e 
N Y U  I n v esti g ati o n al Dr u g  S er vic e  (I D S), c o nt act n u m b er  ( 2 1 2) 2 6 3- 5 0 3 9.  Us e d  
st u d y b ottl es / pills  will  b e  r et ur n e d t o t h e i n v esti g ati o n al p h ar m acist  at  e ac h  
dis p e nsi n g  visit.  Dis p e nsi n g /  R et ur n l o gs  will  b e  us e d  a n d  d oc u m e nt ati o n of  pills  
dis p e ns e d  a n d  pills  r et ur n e d will  b e  d oc u m e nt e d  w e e kl y .
5. 9. 4
R et u r n  o r  D e st r u cti o n  of  St u d y D r u g
At  t h e c o m pl eti o n of  t h e st u d y, t h er e will  b e  a  fi n al r ec o ncili ati o n of  dr u g  s hi p p e d, dr u g  
c o ns u m e d, a n d  dr u g  r e m ai ni n g. T his  r ec o ncili ati o n will  b e  l o g g e d o n  t h e dr u g  
r ec o ncili ati o n f or m, si g n e d a n d  d at e d.  A n y  discr e p a nci es  n ot e d  will  b e  i n v esti g at e d, 
r es ol v e d, a n d  d oc u m e nt e d  pri or  t o r et ur n or  d estr ucti o n  of  u n us e d  st u d y dr u g.  Dr u g  
d estr o y e d  o n  sit e will  b e  d oc u m e nt e d  i n t h e st u d y fil es.
6
St u d y P r o c e d u r e s:
P a g e 2 7


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
Visit  1
Visit  2
Visit  3
Visit  4
Visit  5
Visit  6
Visit  7
Visit  8
Visit 9
Visit  1 0
Visit  1 1
W e ek  - 3- 0
W e ek  0
W e ek  1
W e ek  2
W e ek  3
W e ek  4
W e ek  6
W e ek  7
W e ek  8
W e ek  9
W e ek  1 0
S t u d y 
Pr oc e d ur es  
a n d  
Ass ess m e nts
S cr e e ni n g
B as eli n e  
1
Tr e at m e nt  (L D X or  P B O)  1
E O T 1
E n d  of  
P B O
W as h o ut/  
B as eli n e 2
Tr e at m e nt  (L D X or  P B O)  2
E O T 2
S C R E E NI N G
C o ns e nt
X
D e m o gr a p hics
X
M .I. N.I
X
A C D S  v 1. 2
X
M e dic al  
Hist or y
X
P syc hi atric 
Hist or y
X
M e dic al  
R evi e w  of  
Syst e ms
X
P hysic al  Ex a m
X
H e m at ol o g y,  
C h e mistry,  
Uri n alysis,  
a n d  U D S
X
U ri n e 
Pr e g n a ncy  
T est
X
E C G
X
R evi e w  
Eli gi bility
X
X
X
E F FI C A C Y
A D H D- R S
X
X
X
X
X
X
X
X
X
X
B arkl ey  S C T  
Sc al e
X
X
X
X
X
X
X
X
X
X
C G I- S
x
X
X
X
X
X
X
X
X
X
S A F E T Y
Vit al Si g ns
X
X
X
X
X
X
X
X
X
X
X
C- S S R S
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
X
X
X
X
A dv ers e  
Ev e nts
X
X
X
X
X
X
X
X
X
X
X
N E U R O P S Y C H OL O GI C AL  B A T T E R Y/ E X E C U TI V E  F U N C TI O NI N G
C A N T A B  A D H D
x
X
X
X
W AI S- C O DI N G
&  S Y M B OL 
S E A R C H
X
X
X
X
B RI E F- A
X
X
X
X
B FI S
X
X
X
X
O N- T O P
X
O T H E R
D os e  Dis p e ns e/ 
A dj ust m e nt
X
X
X
X
X
X
X
Dr u g  
Acc o u nt a bility
X
X
X
X
X
X
X
X
X
P a g e 2 8


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
S T U D Y  VI SI T  S C H E D U L E:  T his is  a  t w o p art  st u d y. P ati e nts  will  si g n t his c o ns e nt f or m 
a n d  b e  as k e d  t o d o  t h e f oll o wi n g: Visit  t h e st u d y d oct or  w e e kl y  o v er  a  1 2- w e e k  p er i o d, 
c o m m u nic at e o v er  t h e p h o n e  b et w e e n visits 6 a n d 7 a n d a p pr o xi m at el y 1 w e e k aft er visit 
1 0, a n d  f oll o w st u d y i nstr ucti o ns. I n a d diti o n,  p ati e nts  w h o  p artici p at e  i n t h e s ec o n d p art  
of  t h e st u d y will  b e  as k e d  t o t a k e st u d y dr u g  as  i nstr uct e d at  t h e s a m e ti m e e ac h  d a y.  
P ati e nt  will  h a v e  t h eir bl o o d  dr a w n  o nc e  i n t h e st u d y a b o ut  1 0 mls  will b e  c oll ect e d f or 
h e m at ol o g y  a n d  bl o o d  c h e mistr y.
6. 1
Vi sit  1  ( S cr e e ni n g)  W e e k  - 3 t o W e e k  0
Scr e e ni n g  ( Visit 1)  ( P h e n ot y p e P h as e):  I nf or m e d c o ns e nt, d e m o gr a p hics,  
m e dic al / ps yc hi atric  hist or y,  p h ysic al  e x a m,  r e vi e w of  s yst e ms, 1 2-l e a d  
el ectr oc ar di o gr a m  ( E C G), vit al  si g ns, A D H D  di a g n osis  vi a  A C D S  v 1. 2,  M.I. N.I 
( ass ess m e nt of  ot h er  A xis-I  ps yc hi atric  di a g n osis),  l a b or at or y t esti n g ( h e m at ol o g y, 
bl o o d  c h e mistr y a n d  uri n al ysis),  uri n e  pr e g n a nc y  scr e e n (f or f e m al e p artici p a nts),  
uri n e  t o xic ol o g y scr e e n, Cli nic al  Gl o b al  I m pr essi o ns Sc al e  ( C GI) [ 2 2], C- S S R S,  
N e ur o ps yc h ol o gic al  B att er y,  a n d  pri or  a n d  c o nc o mit a nt m e dic ati o ns  ( C M)) 
6. 2
Vi sit  2  ( B a s eli n e 1) D a y  0
B as e li n e visit:  D uri n g t his visit s u bj ects will h a v e all t ests / pr oc e d ur es c o m pl et e d 
a n d r e vi e w e d. W e will r e vi e w m e dic al hist or y, a n y c urr e nt of a d v ers e e v e nts ( A E) 
a n d c o nc o mit a nt m e dic ati o ns ( C M) si nc e scr e e ni n g visit.  W e will p erf or m vit al si g ns 
a n d C- S S R S. W e will e ns ur e c o m pl eti o n of a n y ass ess m e nts n ot fi nis h e d d uri n g t h e 
scr e e ni n g visit. S u bj ects will b e gi v e n m e dic ati o n t o t a k e t h e n e xt m or ni n g if t h e y 
ar e f o u n d t o h a v e b ot h A D H D a n d S C T. St u d y M e dic ati o n is n ot dis p e ns e d u ntil all 
ass ess m e nts a n d pr oc e d ur e ar e c o m pl et e f or t h e b as eli n e visit 
N ot e:  If at t h e e n d of t his  b as eli n e visit , t h e p ati e nt  is f o u n d t o h a v e  b ot h  A D H D  a n d  
S C T;  t h e y will b e  i n vit e d t o c o nti n u e t o t h e s ec o n d p art  of  t h e st u d y. If t h e p ati e nt  
h as  b ot h  A D H D  a n d S C T,  h e /s h e  will  b e  gi v e n  St u d y  M e dic ati o n  ( V y v a ns e or  
pl ac e b o)  t o t a k e t h e n e xt  m or ni n g.  Pl ac e b o  l o o ks j ust li k e V y v a ns e  b ut  h as  n o  acti v e  
i n gr e di e nts, li k e a  s u g ar pill.  T h e  st u d y m e dic ati o n  c a n b e  t a k e n wit h or  wit h o ut 
f o o d at  t h e s a m e ti m e e v er y  d a y.
P a g e 2 9


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
6. 3
Vi sit s 3, 4, & 5 ( T r e at m e nt) D a y 7 ± 2,  D a y 14 ± 2, a n d D a y 2 1 ± 2 ; W e e k s  1- 3
Visits 3, 4, a n d 5 will occ ur at 7, 1 4, a n d 2 1 d a ys ( ± 2 d a ys) fr o m B as eli n e T h es e  visits  
will c o nsist  of  A D H D- R S  wit h  pr o m pts,  B ar kl e y  S C T  Sc al e,  C GI,  vit al  si g ns, a n d  
ass ess m e nt  of  a d v ers e  e v e nts  ( A E) a n d  c o nc o mit a nt m e dic ati o ns  ( C M). St u d y  
M e dic ati o n  is dis p e ns e d.
6. 4 Vi sit  6  ( EO T 1)  D a y 2 8± 2;  W e e k 4
Visit  6  will  c o nsist of  A D H D- R S  wit h  pr o m pts,  B ar kl e y  S C T  Sc al e,  B RI E F- A,  B ar kl e y  
F u ncti o n al  I m p air m e nt Sc al e  ( B FI S), n e ur o ps yc h ol o gic al b att er y,  C GI,  vit al  si g ns, 
ass ess m e nt  of  a d v ers e  e v e nts  ( A E) a n d  c o nc o mit a nt m e dic ati o ns  ( C M). St u d y 
M e dic ati o n  is dis p e ns e d.  Dr u g  acc o u nt a bilit y  p erf or m e d.  P ati e nt  will  r ec ei v e t w o 
st u d y m e dic ati o n  b ottl es.
6. 5
T el e p h o n e Vi sit - D a y 3 5± 2 ; W e e k  5
St u d y  C o or di n at or  will  c all t h e p ati e nt  t o as k  a b o ut  s af et y a n d  c o m pli a nc e. W e  will  
as k  t h e m; h o w  h a d  t h e y b e e n  f e eli n g si nc e t h eir l ast visit.  W e  will  d oc u m e nt  a n y  
a d v ers e  e v e nts,  c o nc o mit a nt m e dic ati o ns  a n d  m e dic ati o n  c o m pli a nc e. St u d y  
c o or di n at or will  g o  o v er  i nstr ucti o ns r e g ar di n g st u d y m e dic ati o n  a n d  r e mi n d 
p ati e nt  of  t h eir n e xt  a p p oi nt m e nt.
6. 6 
Vi sit  7  ( B a s eli n e 2) D a y 4 2 ± 2; W e e k 6
Visit  7  will  c o nsist of A D H D- R S  wit h  pr o m pts,  B ar kl e y  S C T  Sc al e,  B RI E F- A,  B ar kl e y  
F u ncti o n al  I m p air m e nt Sc al e  ( B FI S), n e ur o ps yc h ol o gic al b att er y,  C GI,  vit al  si g ns, 
ass ess m e nt  of  a d v ers e  e v e nts  ( A E) a n d  c o nc o mit a nt m e dic ati o ns  ( C M). St u d y  
M e dic ati o n  is dis p e ns e d.  Dr u g  acc o u nt a bilit y  is p erf or m e d.
6. 7
Vi sit s 8, 9, & 1 0 ( T r e at m e nt) D a y 4 9 ± 2,  D a y 5 6± 2, a n d D a y 6 3 ± 2 ; W e e k s  7- 9
Visits  8  t hr o u g h 1 0 will  c o nsist of  t h e A D H D- R S  wit h  pr o m pts,  B ar kl e y  S C T  Sc al e,  C GI,  
vit al  si g ns, ass ess m e nt  of  a d v ers e  e v e nts  ( A E) a n d  c o nc o mit a nt m e dic ati o ns  ( C M). 
St u d y  M e dic ati o n  is dis p e ns e d.  Dr u g  acc o u nt a bilit y  is p erf or m e d
P a g e 3 0


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
6. 8
Vi sit  1 1  E n d  of  T r e at m e nt 2 ; D a y 7 0± 2  W e e k  1 0
E n d  of  tr e at m e nt will c o nsist of  A D H D- R S  wit h  pr o m pts,  B ar kl e y S C T  Sc al e, B RI E F- A,  
B ar kl e y F u ncti o n al  I m p air m e nt Sc al e ( B FI S), C- S S R S, n e ur o ps yc h ol o gic al  b att er y,  C GI,  
vit al  si g ns, ass ess m e nt  of  a d v ers e  e v e nts  ( A E) a n d  c o nc o mit a nt m e dic ati o ns  ( C M). 
Dr u g  acc o u nt a bilit y  is p erf or m e d.
6. 9
F oll o w- U p T el e p h o n e / E n d of St u d y- Vi sit  D a y 7 7± 2 ; W e e k  1 1
St u d y  C o or di n at or  will  c all t h e p ati e nt  t o as k  h o w t h e y b e e n  f e eli n g si nc e t h eir l ast 
visit.  W e  will  d oc u m e nt  a n y  a d v ers e  e v e nts,  c o nc o mit a nt m e dic ati o ns .
7
St ati sti c al  Pl a n
Dr.  F ar o n e  will  c o n d uct t he  st atistic al a n al ysis  of  t his st u d y.
St e p h e n  V.  F ar a o n e,  P h. D.
Pr of ess or  of  Ps yc hi atr y  a n d  of  N e ur osci e nc e  &  P h ysi ol o g y  
S U N Y  U pst at e  M e dic al  U ni v ersit y
7 5 0  E ast  A d a ms  St.  S yr ac us e,  N Y  1 3 2 1 0  
sf ar a o n e @c hil d ps yc hr es e arc h. or g
3 1 5- 4 6 4- 3 1 1 3,  ( 3 1 5) 8 4 9- 1 8 3 9  (f a x)
7. 1
S a m pl e  Si z e D et e r mi n ati o n
P h as e  I: R ecr uit m e nt  a n d  S el ecti o n  of  S C T  c as es ( P h e n ot y p e p h as e)
W e  pl a n  t o r ecr uit 1 2 0  a d ults  ( 2 0 % scr e e n f ail r at e) t o e v al u at e  at  t h e scr e e ni n g  
visit;  a p pr o xi m at el y  1 0 0 a d ults  wit h  A D H D  at  t w o sit es ( N Y U a n d  M o u nt  Si n ai)  t o 
i d e ntif y 5 0  S C T +  a n d  5 0  S C T-.  T h es e  p ati e nts  will  b e  e v al u at e d  wit h  cli nic al  
m e as ur es  of  S C T  ( B ar kl e y S C T  Sc al e),  A D H D  ( A D H D- R S wit h  pr o m pts),  e x ec uti v e  
f u ncti o n ( B RI E F- A),  ass ess m e nt  of  ot h er  ps yc hi atric  dis or d ers  ( M.I. N.I) gl o b al  
i m p air m e nt ( C GI), f u ncti o n al i m p air m e nt ( FI R S- Q S),  s uici d alit y ( C- S S R S), a n d  
n e ur o ps yc h ol o gic al  f u ncti o n ( n e ur o ps yc h ol o gic al b att er y).  O nl y  p ati e nts  i n t h e S C T +  
c o h ort will  e nt er  t h e tr e at m e nt p h as e  of  t h e pr ot oc ol.
P h as e  II: Tr e at m e nt  P h as e
W e  ar e  pr o p osi n g  a  2 -sit e ( N Y U a n d  M o u nt  Si n ai)  st u d y of  L D X  i n 5 0  a d ults  wit h  
P a g e 3 1


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
A D H D  +  S C T.  T h e  st u d y will  b e  a  d o u bl e- bli n d,  1 0- w e e k,  cr oss- o v er tr e at m e nt tri al 
of  L D X  ( 4 w e e ks;  3 0  –  7 0  m g / d a y)  vs.  pl ac e b o  ( 4 w e e ks)  wit h  a n  i nt er v e ni n g si n gl e-
bli n d  pl ac e b o  w as h o ut p eri o d  ( 2 w e e ks).  D uri n g  t h e L D X  tr e at m e nt e p oc h,  L D X  
tr e at m e nt will  b e i niti at e d at a  d os e  of 3 0 m g / d a y at  Visit  2  a n d c a n b e titr at e d u p  
(i n t h e j u d g m e nt of  t h e i n v esti g at or) i n i ncr e m e nts of  2 0 m g,  b as e d  u p o n  cli nic al 
r es p o ns e a n d  t ol er a bilit y, t o 5 0 m g / d a y at  Visit  3  a n d 7 0 m g / d a y  at  Visit  4.  S u bj ects  
r ec ei vi n g d ail y  d os es  of  5 0 m g  or  7 0 m g  of  L D X  will  b e  all o w e d  t o d o w n  titr at e o n e  
d os a g e  st e p of  2 0 m g  d uri n g  Visits  2- 4  if (i n t h e j u d g m e nt of  t h e i n v esti g at or) t h e y  
ar e  h a vi n g  iss u es i n t ol er a bilit y. T h e  hi g h est eff ecti v e  d os e  of L D X  will  t h e n b e  
m ai nt ai n e d  u ntil  Visit  4.  P ati e nts  will  b e  s e e n w e e kl y  t hr o u g h o ut t h e tri al.
7. 2
St ati sti c al M et h o d s
P h e n ot y p e  P h as e:  C o m p aris o ns  b et w e e n  t h e a d ult  A D H D  p ati e nts  c o h orts wit h  S C T  
a n d  wit h o ut  S C T  i n t er ms of  A D H D  s y m pt o ms (t ot al, i n att e nti v e a n d  h y p er acti v e-  
i m p ulsi v e, s y m pt o ms of  e x ec uti v e f u ncti o n  ( B RI E F G E C, m et ac o g niti o n,  b e h a vi or al  
r e g ul ati o n sc al es a n d  s u bsc al es: I n hi bit, S hift,  E m oti o n al  C o ntr ol,  I niti at e, W or ki n g  
M e m or y,  Pl a n / Or g a ni z e,  Or g a niz ati o n  of  M at eri als,  M o nit or),  n e ur o ps yc h ol o gic al  
t ests ( C A N T A B A D H D  m o d ul e,  W AI S  C o di n g  a n d  S y m b ol  S e arc h  a n d  Att e nti o n  
N et w or k  T est  ( A N T), a n d  i m p air m e nt ( o n B ar kl e y  F u ncti o n al I m p air m e nt  Sc al e  
( B FI S)) will b e  e x a mi n e vi a  O n e  W a y  A N O V A  .
Tr e at m e nt  P h as e:  C h a n g es  i n o utc o m e  r ati n gs i n t h e p ati e nts  i n t h e tr e at m e nt p h as e  
wit h  L D X  a n d  pl ac e b o  will  b e  m o d el e d  wit h  l o n git u di n al g e n er aliz e d  esti m ati n g  
e q u ati o n  ( G E E) mi x e d  r e gr essi o n m o d els  usi n g  S T A T A  1 2. 0  [ St at a C or p, 2 0 1 1  # 2 5 8 5 6]  
wit hi n  t h e fr a m e w or k of  t h e g e n er al  li n e ar m o d el  ( G L M). T h e  G L M  all o ws  us    
fl e xi bilit y i n m o d eli n g  t h e o utc o m e  v ari a bl e  b y  c h o osi n g t h e a p pr o pri at e  distri b uti o n  
a n d  li n k f u ncti o n. E ac h  m o d el  will  pr e dict  o utc o m e  sc or es fr o m tr e at m e nt gr o u p   
( dr u g vs.  pl ac e b o),  st u d y visit  ( or di n al pr e dict or),  or d er  ( dr u g or  pl ac e b o  first) a n d   
t h e t w o a n d  t hr e e- w a y i nt er acti o ns a m o n g:  tr e at m e nt gr o u p,  visit,  a n d  or d er.  W e  will  
first t est f or or d er eff ects  a n d  dr o p  eff ects  t h at ar e  n ot  si g nific a nt at  p  <. 0 5.  T h e  visit  
b y  tr e at m e nt i nt er acti o n i n dic at es if t h e r e d ucti o n i n s y m pt o ms o v er  ti m e   
si g nific a ntl y diff ers  b et w e e n  dr u g  a n d  pl ac e b o.  O ur  pri m ar y  a n al ys es  will  b e  i nt e nti o n 
P a g e 3 2


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
t o tr e at (I T T) b ut  w e  will  e x pl or e  t h e d at a  wit h  l ess c o ns er v ati v e p er pr ot oc ol 
a n al ys es  t o ass ur e  t h at w e d o  n ot miss  a n y  si g n als i n t h e d at a.  B ec a us e  t his is a  
r a n d o mi z e d tri al, w hic h  f oll o ws s u bj ects o v er  a  s h ort p eri o d  of  ti m e, missi n g  d at a  is 
n ot  e x p ect e d  t o i m p act o ur  a n al ys es.  S h o ul d  t his b ec o m e a n  iss u e, w e will  i m p ut e d at a  
usi n g  S T A T A’s  i m p ut e pr oc e d ur e.  Usi n g  l o gistic r e gr essi o n, a  r es p o n d er a n al ysis will  
b e  c o n d uct e d usi n g  pr e- h oc  pri ori  crit eri a f or tr e at m e nt r es p o ns e ( 3 0 %) d ecr e as es  i n 
t ot al A D H D- R S  a n d  B ar kl e y  S C T  sc or es). T h es e  will  b e l ast  o bs er v ati o n  c arri e d 
f or w ar d ( L O C F) e n d p oi nt  m o d els  t h at pr e dict  r es p o n d er st at us ( y es / n o) fr o m dr u g  
gr o u p,  or d er  a n d  t h e dr u g  b y  or d er  i nt er acti o n. B as eli n e  s y m pt o m sc or es will  b e  
i ncl u d e d as  c o v ari at es.
S af et y  A n al ysis:  V ar i a bl es t o b e  s u m m ariz e d a n d  list e d i ncl u d e vit al si g ns, a d v ers e  
e v e nts,  cli nic al l a b or at or y r es ults, E C G  r e a di n gs, a n d  t h e C- S S R S.  All  a d v ers e  e v e nts  
r es ults will  b e  t a b ul at e d i n m a n uscri pts  al o n g wit h  si g nific a nc e t esti n g usi n g  t h e 
a p pr o pri at e  g e n er al  li n e ar m o d el.  T h es e  m o d els  will  us e  L O C F  e n d p oi nt  a n al ys es  wit h  
t er ms f or dr u g,  or d er  a n d  t h e dr u g  b y  or d er  i nt er acti o n
7. 3
S u bj e ct  P o p ul ati o n( s)  f o r A n al y si s
All  s u bj ects will  b e e nt er e d i nt o t h e a n al ysis  i ncl u di n g:
All-r a n d o mi z e d  p o p ul ati o n:  A n y  s u bj ect r a n d o miz e d i nt o t h e st u d y, r e g ar dl ess of 
w h et h er  t h e y r ec ei v e d st u d y dr u g
All-tr e at e d  p o p ul ati o n:  A n y  s u bj ect r a n d o miz e d i nt o t h e st u d y t h at r ec ei v e d at  l e ast 
o n e  d os e  of  st u d y dr u g
Pr ot oc ol-c o m pli a nt p o p ul ati o n:  A n y  s u bj ect w h o  w as  r a n d o miz e d a n d r ec ei v e d  t h e 
pr ot oc ol  r e q uir e d st u d y dr u g  e x p os ur e  a n d  r e q uir e d pr ot oc ol  pr oc essi n g
8
S af et y  a n d  A d v e r s e  E v e nt s
8. 1
D efi niti o n s
U n a nti ci p at e d  P r o bl e m s  I n v ol vi n g Ri s k t o  S u bj e ct s  o r Ot h e r s
A n y  i nci d e nt, e x p eri e nc e,  or  o utc o m e t h at  m e ets  all  of  t h e f oll o wi n g crit eri a:
P a g e 3 3


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

U n e x p ect e d  i n n at ur e,  s e v erit y, or  fr e q u e nc y (i. e. n ot  d escri b e d  i n st u d y-r el at e d 
d oc u m e nts  s uc h as  t h e I R B- a p pr o v e d pr ot oc ol  or  c o ns e nt f or m, t h e i n v esti g at ors 
br oc h ur e,  etc.)

R el at e d  or  p ossi bl y  r el at e d t o p artici p ati o n  i n t h e r es e arc h (i. e. p ossi bl y  r el at e d 
m e a ns  t h er e is a  r e as o n a bl e p ossi bilit y  t h at t h e i nci d e nt e x p eri e nc e,  or  o utc o m e  m a y  
h a v e  b e e n  c a us e d b y  t h e pr oc e d ur es  i n v ol v e d i n t h e r es e arc h).

S u g g ests  t h at t h e r es e arc h pl ac es  s u bj ects or  ot h ers  at  gr e at er  ris k of  h ar m  
(i ncl u di n g p h ysic al,  ps yc h ol o gic al,  ec o n o mic,  or  s oci al h ar m).
A d v e r s e  E v e nt
A n  a d v e r s e  e v e nt  ( A E) is a n y  s y m pt o m, si g n, ill n ess or  e x p eri e nc e  t h at d e v el o ps  or 
w ors e ns  i n s e v erit y d uri n g  t h e c o urs e of  t h e st u d y. I nt erc urr e nt ill n ess es or  i nj uri es s h o ul d 
b e  r e g ar d e d as  a d v ers e  e v e nts.  A b n or m al  r es ults of  di a g n ostic  pr oc e d ur es  ar e  c o nsi d er e d 
t o b e  a d v ers e  e v e nts if  t h e a b n or m alit y:

r es ults i n st u d y wit h dr a w al

is ass oci at e d  wit h  a  s eri o us a d v ers e  e v e nt

is ass oci at e d  wit h  cli nic al si g ns or  s y m pt o ms

l e a ds t o a d diti o n al  tr e at m e nt or  t o f urt h er di a g n ostic  t ests

is c o nsi d er e d b y  t h e i n v esti g at or t o b e  of  cli nic al si g nific a nc e
S e ri o u s  A d v e r s e  E v e nt
A d v ers e  e v e nts  ar e  cl assifi e d as s eri o us  or  n o n-s eri o us.  A  s e ri o u s  a d v e r s e  e v e nt  is a n y  A E  
t h at is:

f at al

lif e-t hr e at e ni n g

r e q uir es or  pr ol o n gs  h os pit al  st a y

r es ults i n p ersist e nt  or  si g nific a nt dis a bilit y  or  i nc a p acit y

a  c o n g e nit al a n o m al y  or  birt h  d ef ect

a n  i m p ort a nt m e dic al  e v e nt
P a g e 3 4


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
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 el y lif e t hr e at e ni n g, b ut  ar e  
cl e arl y of  m aj or  cli nic al si g nific a nc e.  T h e y  m a y  j e o p ar diz e t h e s u bj ect a n d m a y  r e q uir e 
i nt er v e nti o n t o pr e v 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 o v e.  F or  e x a m pl e,  dr u g  
o v er d os e  or  a b us e,  a  s ei z 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 of  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 all y b e  c o nsi d er e d 
s eri o us.
All  a d v ers e  e v e nts  t h at d o  n ot  m e et  a n y  o f t h e crit eri a f or s eri o us s h o ul d b e  r e g ar d e d as
n o n- s e ri o u s  a d v e r s e  e v e nt s .
A d v e r s e  E v e nt  R e p o rti n g  P e ri o d
T h e  st u d y p eri o d  d uri n g  w hic h  a d v ers e  e v e nts  m ust  b e  re p ort e d is  n or m all y  d efi n e d  as  t h e 
p eri o d  fr o m t h e i niti ati o n of  a n y  st u d y pr oc e d ur es  t o t h e e n d of  t h e st u d y tr e at m e nt f oll o w- 
u p.  F or  t his st u d y, t h e st u d y tr e at m e nt f oll o w- u p is d efi n e d  as  3 0  d a ys  f oll o wi n g t h e l ast 
a d mi nistr ati o n  of  st u d y tr e at m e nt.
P r e e xi sti n g  C o n diti o n
A  pr e e xisti n g  c o n diti o n is o n e  t h at is pr es e nt  at  t h e st art of  t h e st u d y. A  pr e e xisti n g  
c o n diti o n s h o ul d b e  r ec or d e d as  a n  a d v ers e  e v e nt  if t h e fr e q u e nc y, i nt e nsit y, or  t h e 
c h ar act er of  t h e c o n diti o n w ors e ns  d uri n g  t h e st u d y p eri o d.
G e n e r al  P h y si c al  E x a mi n ati o n  Fi n di n g s
At  scr e e ni n g, a n y  cli nic all y si g nific a nt a b n or m alit y  s h o ul d b e  r ec or d e d as  a  pr e e xisti n g  
c o n diti o n. At  t h e e n d  of  t h e st u d y, a n y  n e w  cli nic all y si g nific a nt fi n di n gs / a b n or m aliti es 
t h at m e et  t h e d efi niti o n  of  a n  a d v ers e  e v e nt  m ust  als o  b e  r ec or d e d a n d  d oc u m e nt e d  as  a n  
a d v ers e  e v e nt.
P o st- st u d y  A d v e r s e  E v e nt
All  u nr es ol v e d  a d v ers e  e v e nts  s h o ul d b e  f oll o w e d b y  t h e i n v esti g at or u ntil  t h e e v e nts  ar e  
r es ol v e d, t h e s u bj ect is l ost t o f oll o w- u p, or  t h e a d v ers e  e v e nt  is ot h er wis e  e x pl ai n e d.  At  
t h e l ast sc h e d ul e d visit,  t h e i n v esti g at or s h o ul d i nstr uct e ac h  s u bj ect t o r e p ort a n y
P a g e 3 5


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
s u bs e q u e nt e v e nt(s)  t h at t h e s u bj ect, or  t h e s u bj ect’s p ers o n al  p h ysici a n,  b eli e v es  mi g ht  
r eas o n a bl y  b e  r el at e d t o p artici p ati o n  i n t his st u d y. T h e  i n v esti g at or s h o ul d n otif y  t h e 
st u d y s p o ns or of  a n y  d e at h  or  a d v ers e  e v e nt  occ urri n g  at  a n y  ti m e aft er  a  s u bj ect h as  
disc o nti n u e d  or  t er mi n at e d st u d y p artici p ati o n t h at  m a y  r e as o n a bl y b e  r el at e d t o t his 
st u d y. T h e  s p o ns or s h o ul d als o  b e  n otifi e d  if t h e i n v esti g at or s h o ul d b ec o m e  a w ar e  of  t h e 
d e v el o p m e nt  of  c a nc er or  of  a  c o n g e nit al a n o m al y i n a  s u bs e q u e ntl y c o nc ei v e d offs pri n g of  
a  s u bj ect t h at h as  p artici p at e d  i n t his st u d y.
A b n o r m al  L a b o r at o r y  V al u e s
A  cli nic al l a b or at or y a b n or m alit y s h o ul d  b e  d oc u m e nt e d  as  a n  a d v ers e e v e nt  if a n y  o n e  of  
t h e f oll o wi n g c o n diti o ns is m et:

T h e  l a b or at or y a b n or m alit y  is n ot  ot h er wis e  r ef ut e d b y a  r e p e at t est t o c o nfir m t h e 
a b n or m alit y

T h e  a b n or m alit y  s u g g ests a  dis e as e  a n d / or  or g a n  t o xicit y

T h e  a b n or m alit y  is of  a  d e gr e e  t h at r e q uir es acti v e  m a n a g e m e nt;  e. g. c h a n g e  of  d os e,  
disc o nti n u ati o n  of  t h e dr u g,  m or e  fr e q u e nt f oll o w- u p ass ess m e nts,  f urt h er di a g n ostic  
i n v esti g ati o n, etc.
H o s pit ali z ati o n,  P r ol o n g e d  H o s pit ali z ati o n  o r  S u r g e r y
A n y  a d v ers e  e v e nt  t h at r es ults i n h os pit aliz ati o n  or  pr ol o n g e d  h os pit aliz ati o n  s h o ul d b e  
d oc u m e nt e d  a n d  r e p ort e d as  a  s eri o us a d v ers e  e v e nt  u nl ess  s p ecific all y i nstr uct e d 
ot h er wis e  i n t his pr ot oc ol.  A n y  c o n diti o n r es p o nsi bl e f or s ur g er y s h o ul d b e  d oc u m e nt e d  as  
a n  a d v ers e  e v e nt  if t h e c o n diti o n m e ets  t h e crit eri a f or a n  a d v ers e  e v e nt.
N eit h er  t h e c o n diti o n, h os pit ali z ati o n,  pr ol o n g e d  h os pit aliz ati o n,  n or  s ur g er y ar e  r e p ort e d 
as  a n  a d v ers e  e v e nt  i n t h e f oll o wi n g circ u mst a nc es:

H os pit ali z ati o n  or  pr ol o n g e d  h os pit aliz ati o n  f or di a g n ostic  or  el ecti v e  s ur gic al 
pr oc e d ur es  f or a  pr e e xisti n g  c o n diti o n. S ur g er y  s h o ul d n ot  b e  r e p ort e d as a n  
o utc o m e  of  a n  a d v ers e  e v e nt  if t h e p ur p os e  of  t h e s ur g er y w as  el ecti v e  or  di a g n ostic  
a n d  t h e o utc o m e  w as  u n e v e ntf ul.
P a g e 3 6


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

H os pit ali z ati o n  or  pr ol o n g e d  h os pit aliz ati o n  r e q uir e d t o all o w  effic ac y  m e as ur e m e nt  
f or t h e st u d y.

H os pit ali z ati o n  or  pr ol o n g e d  h os pit aliz ati o n  f or t h er a p y of t h e  t ar g et dis e as e  of  t h e 
st u d y, u nl ess  it is a  w ors e ni n g  or  i ncr e as e i n fr e q u e nc y of  h os pit al  a d missi o ns  as  
j u d g e d b y  t h e cli nic al i n v esti g at or.
8. 2
R e c o r di n g  of  A d v e r s e  E v e nt s
At  e ac h  c o nt act wit h  t h e s u bj ect, t he  i n v esti g at or m ust  s e e k i nf or m ati o n o n  a d v ers e  
e v e nts  b y  s p ecific q u esti o ni n g  a n d,  as  a p pr o pri at e,  b y  e x a mi n ati o n.  I nf or m ati o n o n  
all  a d v ers e  e v e nts  s h o ul d b e  r ec or d e d i m m e di at el y 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 d v ers e  e v e nt  m o d ul e  of  t h e c as e r e p ort f or m ( C R F). All  cl e arl y 
r el at e d 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 
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 s h o ul d b e  gr o u p e d  u n d er  o n e  di a g n osis).
All  a d v ers e  e v e nts  occ urri n g  d uri n g  t h e st u d y p eri o d  m ust  b e  rec or d e d.  T h e  cli nic al 
c o urs e of  e ac h e v e nt  s h o ul d b e  f oll o w e d u ntil  r es ol uti o n, st a biliz ati o n, or  u ntil  it h as  
b e e n  d et er mi n e d  t h at t h e st u d y tr e at m e nt or  p artici p ati o n  is n ot  t h e c a us e. S eri o us  
a d v ers e  e v e nts t h at  ar e  still o n g oi n g  at  t h e e n d  of  t h e st u d y p eri o d  m ust  b e f oll o w e d  
u p  t o d et er mi n e  t h e fi n al o utc o m e.  A n y  s eri o us a d v ers e  e v e nt  t h at occ urs  aft er  t h e 
st u d y p eri o d  a n d  is c o nsi d er e d t o b e  p ossi bl y  r el at e d t o t h e st u d y tr e at m e nt or  st u d y 
p artici p ati o n  s h o ul d b e  r ec or d e d a n d  r e p ort e d i m m e di at el y.
8. 3
R e p o rti n g  of  S e ri o u s  A d v e r s e  E v e nt s a n d  U n a nti ci p at e d  P r o bl e m s
A  s eri o us a d v ers e  e v e nt  ( S A E) i ncl u d es a n y  e v e nt  t h at r es ults i n a n y  of  t h e f oll o wi n g 
o utc o m es:
•
D e at h
•
I niti al or  pr ol o n g e d  i n p ati e nt h os pit aliz ati o n
•
A lif e-t hr e at e ni n g e x p eri e nc e  (t h at is, i m m e di at e ris k of  d yi n g)
•
P ersist e nt  or  si g nific a nt dis a bilit y /i nc a p acit y
•
C o n g e nit al  a n o m al y / birt h  d ef ect
•
Ot h er  m e dic all y  i m p ort a nt e v e nts
P a g e 3 7


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
U n e x p ect e d  a n d  r el at e d S A E will  b e  r e p ort e d t o t h e I R B a n d  wit hi n  5  d a y s aft er  st u d y 
p ers o n n el  b ec o m e  a w ar e  of  t h e e v e nt.  S eri o us  a d v ers e  e v e nts  ( S A E) occ urri n g  aft er  a  
p artici p a nt  is disc o nti n u e d  fr o m t h e st u d y will  o nl y  b e  r e p ort e d if t h e Pri nci p al  I n v esti g at or 
b eli e v es  t h at t h e e v e nt  m a y  h a v e  b e e n  c a us e d b y  t h e st u d y m e dic ati o n  or  a  pr ot oc ol 
pr oc e d ur e.
F o r  N a r r ati v e R e p o rt s  of  S af et y  E v e nt s
If t h e r e p ort is s u p pli e d as  a  n ar r ati v e, t h e mi ni m u m  n ec ess ar y  i nf or m ati o n t o b e  pr o vi d e d  
at  t h e ti m e of  t h e i niti al r e p ort i ncl u d es:

St u d y  i d e ntifi er

St u d y  C e nt er

S u bj ect  n u m b er

A  d escri pti o n  of  t h e e v e nt

D at e  of  o ns et

C urr e nt  st at us

W h et h er  st u d y tr e at m e nt w as  disc o nti n u e d

T h e  r e as o n w h y  t h e e v e nt  is cl assifi e d as  
s eri o us

I n v esti g at or ass ess m e nt  of  t h e ass oci ati o n  
b et w e e n  t h e e v e nt  a n d st u d y  tr e at m e nt
8. 3. 1
I n v e sti g at o r  r e p o rti n g:  n otif yi n g t h e  st u d y s p o n s o r
T h e  f oll o wi n g d escri b es  e v e nts  t h at m ust  b e  re p ort e d  t o t h e st u d y s p o ns or i n a n  e x p e dit e d  
f as hi o n.
I niti al R e p o rt:  wit hi n  2 4  h o u r s:
T h e  f oll o wi n g e v e nts  m ust  b e  re p ort e d  t o S hir e  b y  t el e p h o n e wit hi n  2 4  h o urs  of  a w ar e n ess  
of  t h e e v e nt:

U n a ntici p at e d  pr o bl e ms  r el at e d t o st u d y p artici p ati o n,

S eri o us  a d v ers e  e v e nts,  r e g ar dl ess of  w h et h er  t h e y ar e  u n e x p ect e d.
P a g e 3 8


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
A d diti o n all y,  a n  F D A  F or m  3 5 0 0 A  ( M E D W A T C H F or m; s e e  Att ac h m e nt  [ 5]) m ust  b e  
c om pl et e d  b y  t h e i n v esti g at or a n d  f a x e d t o t h e st u d y S hir e wit hi n  2 4  h o urs.  T h e  
i n v esti g at or s h all m ai nt ai n  a  c o p y of  t h e M E D W A T C H F or m  o n  fil e at  t h e st u d y sit e.
J o e K er k eri n g-  j k er k eri n g @s hir e.c o m 
S hir e  P h ar m ac e utic als
7 2 5  C h est er br o o k  B o ul e v ar d  S 3 C-
1 6
W a y n e,  P A  1 9 0 8 7
F oll o w- u p  r e p o rt:  wit h i n 4 8  h o u r s:
As  a  f oll o w- u p t o t h e i niti al r ep ort,  wit hi n  t h e f oll o wi n g 4 8  h o urs  of  a w ar e n ess of  t h e 
e v e nt,  t h e i n v esti g at or s h all pr o vi d e  f urt h er i nf or m ati o n, as  a p plic a bl e,  o n  t h e 
u n a ntici p at e d  e v e nt  or  t h e u n a ntici p at e d  pr o bl e m  i n t h e f or m of  a  writt e n  n arr ati v e.  
T his  s h o ul d i ncl u d e a  c o p y of  t h e c o m pl et e d U n a ntici p at e d  Pr o bl e m  f or m, a n d  a n y  
ot h er  di a g n ostic  i nf or m ati o n t h at will  assist  t h e u n d erst a n di n g  of  t h e e v e nt.
Si g nific a nt  n e w  i nf or m ati o n o n  o n g oi n g  u n a ntici p at e d  a d v ers e  e v e nts  s h all b e  
pr o vi d e d  pr o m ptl y  t o t h e st u d y s p o ns or.
Ot h e r  R e p o rt a bl e  e v e nt s:

D e vi ati o n s f r o m  t h e st u d y p r ot o c ol
D e vi ati o ns  fr o m t h e pr ot oc ol  m ust  r ec ei v e b ot h  S p o ns or  a n d  t h e i n v esti g at or’s I R B 
a p pr o v al  b ef or e  t h e y ar e  i niti at e d. A n y  pr o t oc ol d e vi ati o ns  i niti at e d wit h o ut  
S p o ns or  a n d  t h e i n v esti g at or’s I R B a p pr o v al  t h at m a y  aff ect  t h e sci e ntific s o u n d n ess 
of  t h e st u d y, or  aff ect  t h e ri g hts, s af et y, or  w elf ar e  of  st u d y s u bj ects, m ust  b e 
r e p ort e d t o t h e S p o ns or  a n d  t o t h e i n v esti g at or’s I R B as  s o o n as  a  p ossi bl e,  b ut  n o  
l at e r t h a n 5  w o r ki n g  d a y s  of  t h e pr ot oc ol  d e vi ati o n.

Wit h d r a w al  of  I R B a p p r o v al
A n  i n v esti g at or s h all r e p ort t o t h e s p o ns or a  wit h dr a w al  of a p pr o v al  b y  t h e 
i n v esti g at or’s r e vi e wi n g I R B as  s o o n as  a  p ossi bl e,  b ut  n o  l at e r t h a n 5  w o r ki n g  
d a y s  of  t h e I R B n otific ati o n  of  wit h dr a w al  of  a p pr o v al.
P a g e 3 9


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
8. 3. 2
I n v e sti g at o r r e p o rti n g: n otif yi n g  t h e I R B
F e d er al  r e g ul ati o ns r e q uir e ti m el y r e p orti n g b y  i n v esti g at ors t o t h eir l oc al I R B of  
u n a ntici p at e d  pr o bl e ms  p osi n g  ris ks t o s u bj ects or  ot h ers.  T h e  f oll o wi n g d escri b es  t h e 
N Y U L M C  I R B r e p orti n g r e q uir e m e nts, t h o u g h I n v esti g at ors at  p artici p ati n g  sit es ar e  
r es p o nsi bl e f or m e eti n g  t h e s p ecific r e q uir e m e nts of  t h eir I R B of  r ec or d.
R e p o rt  p r o m ptl y,  b ut n o l at e r  t h a n 5  w o r ki n g d a y s:
R es e arc h ers  ar e  r e q uir e d t o s u b mit r e p orts of  t h e f oll o wi n g pr o bl e ms  pr o m ptl y  b ut  n o  
l at er t h a n 5  w or ki n g  d a ys  fr o m t h e ti m e t h e i n v esti g at or b ec o m es  a w ar e  of t h e  e v e nt:

U n a nti ci p at e d  p r o bl e m s  i n cl u di n g a d v e r s e  e v e nt s  t h at a r e  u n e x p e ct e d  a n d  
r el at e d
– U n e x p ect e d : A n  e v e nt  is “ u n e x p ect e d” w h e n  its s p ecificit y a n d  s e v erit y ar e  n ot  
acc ur at el y  r efl ect e d i n t h e pr ot oc ol-r el at e d  d oc u m e nts,  s uc h as  t h e I R B- a p pr o v e d 
r es e arc h pr ot oc ol,  a n y  a p plic a bl e  i n v esti g at or br oc h ur e,  a n d  t h e c urr e nt I R B- 
a p pr o v e d  i nf or m e d c o ns e nt d oc u m e nt  a n d  ot h er  r el e v a nt s o urc es of  i nf or m ati o n, 
s uc h as  pr o d uct  l a b eli n g a n d  p ac k a g e  i ns erts.
– R el at e d  t o t h e r es e arc h pr oc e d ur es : A n  e v e nt  is r el at e d t o t h e r es e arc h 
pr oc e d ur es  if i n t h e o pi ni o n  of  t h e pri nci p al  i n v esti g at or or  s p o ns or, t h e e v e nt  
w as  m or e  li k el y t h a n n ot  t o b e  c a us e d b y  t h e r es e arc h pr oc e d ur es.
– H ar mf ul:  eit h er  c a us e d h ar m  t o s u bj ects or  ot h ers,  or  pl ac e d  t h e m at  i ncr e as e d 
ris k
Ot h e r  R e p o rt a bl e  e v e nt s:
T h e  f oll o wi n g e v e nts  als o  r e q uir e pr o m pt  r e p orti n g t o t h e I R B, t h o u g h n o  l at e r t h a n 5  
w o r ki n g  d a y s :

C o m pl ai nt  of  a  r e s e a r c h  s u bj e ct  w h e n  t h e c o m pl ai nt i n dic at es u n e x p ect e d  ris ks or  
t h e c o m pl ai nt c a n n ot b e  r es ol v e d b y  t h e r es e arc h t e a m.
P a g e 4 0


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

P r ot o c ol d e vi ati o n s  o r  vi ol ati o n s  (i ncl u d es i nt e nti o n al a n d  
ac ci d e nt al / u ni nt e nti o n al d e vi ati o ns fr o m  t h e I R B a p pr o v e d  pr ot oc ol)  f or a n y  of  t h e 
f oll o wi n g sit u ati o ns:
– o n e  or  m or e  p arti ci p a nts w er e  pl ac e d  at  i ncr e as e d ris k of  h ar m
– t h e e v e nt  h as  t h e p ot e nti al  t o occ ur  a g ai n
– t h e d e vi ati o n  w as  n ec ess ar y  t o pr ot ect  a  s u bj ect fr o m i m m e di at e h ar m

B r e a c h  of  c o nfi d e nti alit y

I n c a r c e r ati o n of  a  p a rti ci p a nt  w h e n  t h e r es e arc h w as  n ot  pr e vi o usl y  a p pr o v e d  
u n d er  S u b p art  C  a n d  t h e i n v esti g at or b eli e v es  it is i n t h e b est  i nt er est of t h e s u bj ect 
t o r e m ai n o n  t h e st u d y.

N e w  I nf o r m ati o n i n di c ati n g a  c h a n g e t o  t h e ri s k s  o r  p ot e nti al  b e n efit s  of  t h e 
r es e arc h, i n t er ms of  s e v erit y or  fr e q u e nc y. ( e. g. a n al ysis  i n dic at es l o w er-t h a n- 
e x p ect e d  r es p o ns e r at e or  a  m or e  s e v er e or  fr e q u e nt si d e eff ect;  Ot h er  r es e arc h fi n ds 
ar m  of  st u d y h as  n o  t h er a p e utic v al u e;  F D A  l a b eli n g c h a n g e or wit h dr a w al  fr o m 
m ar k et)
R e p o rti n g  P r o c e s s
T h e  r e p ort a bl e e v e nts n ot e d  a b o v e  will  b e  r e p ort e d t o t h e I R B usi n g  t h e f or m: “ R e p ort a bl e 
E v e nt  F or m”  or  as  a  wr itt e n r e p ort of  t h e e v e nt  (i ncl u di n g a  d escri pti o n  of  t h e e v e nt  wit h  
i nf or m ati o n r e g ar di n g its f ulfill m e nt of  t h e a b o v e  crit eri a, f oll o w- u p /r es ol uti o n a n d  n e e d  
f or r e visi o n t o c o ns e nt f or m a n d / or  ot h er  st u d y d oc u m e nt ati o n).
C o pi es  of  e ac h  r e p ort a n d  d oc u m e nt ati o n of  I R B n otific ati o n  a n d  r ec ei pt will  b e  k e pt  i n t h e 
Cli nic al  I n v esti g at or’s st u d y fil e.
8. 3. 3
S p o n s o r  r e p o rti n g:  N otif yi n g  t h e F D A
S hir e  is r e q uir e d t o r e p ort c ert ai n st u d y e v e nts  i n a n  e x p e dit e d  f as hi o n t o t h e F D A.  T h e  
f oll o wi n g d escri b es  t h e s af et y r e p orti n g r e q uir e m e nts b y  ti m eli n e f or r e p orti n g a n d  
ass oci at e d  t y p e of  e v e nt:
P a g e 4 1


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

Wit hi n  7  c al e n d a r  d a y s  ( vi a t el e p h o n e or  f acsi mil e r e p ort)  
A n y  st u d y e v e nt  t h at is:
–
ass oci at e d  wit h  t h e us e  of  t h e st u d y dr u g
–
u n e x p ect e d,
–
f at al or lif e-t hr e at e ni n g

Wit hi n  1 5  c al e n d a r  d a y s  ( vi a writt e n  r e p ort)  
A n y  st u d y e v e nt  t h at is:
–
ass oci at e d  wit h  t h e us e  of  t h e st u d y dr u g,
–
u n e x p ect e d,  a n d
–
seri o us,  b ut  n ot f at al  or  lif e-t hr e at e ni n g
- or-
–
A  pr e vi o us  a d v ers e  e v e nt  t h at w as n ot  i niti all y d e e m e d r e p ort a bl e b ut  is l at er 
f o u n d t o fit t h e crit eri a f or r e p orti n g (r e p orti n g wit hi n  1 5  c al e n d ar d a ys  fr o m 
w h e n  e v e nt  w as  d e e m e d  r e p ort a bl e).
A n y  fi n di n g fr o m t ests i n l a b or at or y a ni m als  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 i ncl u di n g r e p orts of m ut a g e nicit y,  
t erat o g e nicit y,  or  c arci n o g e nicit y.
A d diti o n al  r e p o rti n g  r e q ui r e m e nt s
S p o ns ors  ar e  als o  r e q uir e d t o i d e ntif y i n I N D s af et y r e p orts all  pr e vi o us  r e p orts c o nc er ni n g 
si mil ar a d v ers e  e v e nts  a n d  t o a n al y z e  t h e si g nific a nc e of  t h e c urr e nt e v e nt  i n li g ht of  t h e 
pr e vi o us  r e p orts.
R e p o rti n g  P r o c e s s
A d v ers e  e v e nts  m a y  b e  su b mitt e d  o n  F D A  F or m  3 5 0 0 A  ( M E D W A T C H F or m;  s e e  
Att ac h m e nt  [ 5]), or  i n a  n arr ati v e  f or m at. If s u p pli e d as  i n a  n arr ati v e  f or m at, t h e mi ni m u m  
i nf or m ati o n t o b e  s u p pli e d is n ot e d  a b o v e  at  t h e b e gi n ni n g  of  s ecti o n 8. 3.  T h e c o nt act  
i nf or m ati o n f or s u b mitti n g r e p orts is n ot e d  b el o w:
P a g e 4 2


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
Mitc h ell  V.  M at his,  M. D.  C A P T  U S P H S  Dir ect or  Di visi o n  of  Ps yc hi atr y  Pr o d ucts  or  C A P T  P a ul
A.  D a vi d,  C hi ef  Pr oj ect  M a n a g e m e nt  St aff,  at  ( 3 0 I) 7 9 6- 1 0 5 8.
8. 3. 4
S p o n s o r r e p o rti n g: N otif yi n g  p a rti ci p ati n g i n v e sti g at o r s
It is t h e r es p o nsi bilit y of  L e a d  Pri nci p al  I n v esti g at or Dr.  A dl er  t o n o tif y S hir e  a n d  Dr.  J eff er y 
N e wc or n,  Pri nci p al  I n v esti g at or at  M o u nt  Si n ai  of  all  a n d a n y  a d v ers e  e v e nt  t h at m e ets  t h e 
F D A  1 5- d a y  r e p orti n g r e q uir e m e nt crit eri a as  n ot e  a b o v e  i n s ecti o n 8. 3. 4.  T h e  s a m e 
m at eri als  a n d  ti m eli n e us e d  t o r e p ort t o t h e F D A  ar e  us e d  f or n otif yi n g  p artici p ati n g  
i n v esti g at ors.
8. 4
U n bli n di n g P r o c e d u r e s
W hil e  t h e s af et y of  t h e s u bj ect al w a ys  c o m es first, it is still i m p ort a nt t o s eri o usl y c o nsi d er 
if u n bli n di n g  t h e st u d y f oll o w- u p a n d  r ef err al is n ec ess ar y  t o e ns ur e  a  s u bj ect’s s af et y.
P ati e nts  will  b e  u n bli n d e d  if i n t h e o pi ni o n  of  t h e i n v esti g at or s u bj ects a d v ers e  e v e nts  or  
c o nti n u e d p artici p ati o n  will  b e  u ns af e  t o t h e s u bj ects. If s u bj ects ar e  e x p eri e nci n g a  d ecli n e  
of  3 0 %  p er  t h e cli nic al ass ess m e nts  c o n d uct e d t h e y will  b e  wit h dr a w n.  P ati e nt  will  b e  
u n bli n d e d  b y  o ur  i n v esti g ati o n al p h ar m acist  t o e ns ur e  s af et y. W e will  m a n a g e  t h e p ati e nt  
a n d  r e p ort t h es e fi n di n g t o o ur  m e dic al  m o nit or.  I n t h e c as e s u bj ect is u n bli n d e d  n ot  d u e  t o 
a n  a d v ers e  e v e nt  w e  will  n otif y  s hir e wit hi n  2 4  h o urs  b y  p h o n e  or  f a x, f oll o w e d b y  a  
writt e n  n arr ati v e  of  t h e e v e nt  wit hi n  4 8  h o urs.
8. 5
St o p pi n g  R ul e s
If s u bj ects ar e  e x p eri e nci n g  a  d ecli n e  of  3 0 %  p er  t h e cli nic al ass ess m e nts  c o n d uct e d t h e y 
will  b e  wit h dr a w n.  P ati e nt  e x p eri e nci n g  a d v ers e  e v e nts  t h at i n t h e o pi ni o n  of  t h e 
i n v esti g at or t h e s u bj ect c a n n o  l o n g er p artici p at e d u e  t o a  c h a n g e i n m e dic al  st at us (e. g.  
e x p eri e nc es  fr o m a d v ers e  e v e nts  b ec o m es  pr e g n a nt  t h e s u bj ect will  b e  disc o nti n u e d  fr o m 
t h e st u d y).
T h es e  ar e  t h e p ossi bl e  r e as o ns f or t er mi n ati o n fr o m t h e st u d y:

A d v ers e  e v e nts

L ac k  of  effic ac y

L ost  t o f oll o w- u p
P a g e 4 3


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

P r e g n a nc y

Wit h dr a w al b y s u bj ect

N o nc o m pli a nc e

Pr ot oc ol  vi ol ati o n

Ot h er
8. 6
M e di c al M o nit o ri n g
Dr.  A dl er  as  t he  l e a d pri nci p al  i n v esti g at or will  o v ers e e  s af et y f or b ot h  N Y U  a n d  M S S M.  It is 
t h e r es p o nsi bilit y of  t h e Pri nci p al  I n v esti g at or t o o v ers e e  t h e s af et y of  t h e st u d y at  his / h er  
sit e a n d  c o m m u nic at e s af et y iss u es as  p er  t h e m o nit ori n g  pl a n.  T his  s af et y m o nit ori n g  will  
i ncl u d e c ar ef ul ass ess m e nt  a n d  a p pr o pri at e  r e p orti n g of  a d v ers e  e v e nts  as  n ot e d  a b o v e,  as  
w ell  as  t h e c o nstr ucti o n a n d  i m pl e m e nt ati o n of  a  sit e d at a  a n d  s af et y- m o nit ori n g pl a n;  
Att ac h m e nt  [ 6] . M e dic al m o nit ori n g  will  i ncl u d e a  r e g ul ar ass ess m e nt  of  t h e n u m b er  a n d  
t y p e of  s eri o us a d v ers e  e v e nts  a n d  a  r e p ort t o b e  s u b mitt e d t o t h e I R B. Dr.  V ats al  G.  
T h a k k ar,  M. D.  is a  Cli nic al  Assist a nt  Pr of ess or  of  Ps yc hi atr y  at  t h e N Y U  Sc h o ol  of  M e dici n e.  
Dr.  T h a k k ar  is b o ar d  c ertifi e d i n ps yc hi atr y  a n d  lic e ns e d t o pr actic e  m e dici n e  i n t h e st at es 
of  N e w  Y or k  a n d C o n n ectic ut.
M e dic al  M o nit or:  V ats al  T h a k k ar  M. D.
3 0 4  P ar k  A v e n u e, 1 1 t h fl o or
N e w  Y or k,  N Y  1 0 0 1 0
T el e p h o n e: 6 4 6- 7 0 6- 7 7 5 7  
F a x: 6 4 6- 7 0 6- 7 7 1 4
St u d y  M o nit o ri n g  Pl a n:
Dr.  A dl er,  as  PI,  will  b e  r es p o nsi bl e f or r e vi e w of  all  as p ects  of  t h e st u d y at  o ur  sit e, a n d  will  
r e vi e w s u bj ect pr o gr ess  w e e kl y,  i ncl u di n g:

R ecr uit m e nt  pr oc e d ur es

I nf or m e d c o ns e nt

R ecr uit m e nt  pr oc e d ur es

Pr ot oc ol  vi ol ati o ns

Occ urr e nc e  a n d  h a n dli n g  of  a d v ers e  eff ects

P ati e nt  O utc o m es

P artici p a nts’  s af et y, pri v ac y  a n d  c o nfi d e nti alit y
P a g e 4 4


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

Pr ot oc ol  vi ol ati o ns

Occ urr e nc e  a n d  h a n dli n g  of  a d v ers e  eff ects

P ati e nt  O utc o m es

P artici p a nts’  s af et y, pri v ac y  a n d  c o nfi d e nti alit y

St u d y  pr o gr ess  t o w ar d r ecr uit m e nt g o als  a n d  p artici p a nt  r et e nti o n / attriti o n 
r at es

R e vi e w  of  n e w  sci e ntific lit er at ur e p erti n e nt  t o t h e s af et y of  p artici p a nts
All  s u bj ect c h arts will  b e  r e vi e w e d f or acc ur ac y  a n d  c o m pl et e n ess o n  a  w e e kl y  b asis.  Als o  
el ectr o nic  d at a  will  b e  e nt er e d  t wic e f or v erific ati o n  p ur p os es.  Dr.  A dl er,  i n c oll a b or ati o n  
wit h  t h e s u bc o ntr acti n g sit e PI,  L e n ar d  A dl er,  M D,  will  d et er mi n e  w h et h er  ris k / b e n efit r ati os 
h a v e c h a n g e d t o t h e e xt e nt  t h at t h e tri al s h o ul d b e  m o difi e d  or  disc o nti n u e d.  S p ecific  
r ec o m m e n d ati o ns f or pr ot oc ol  m o dific ati o ns,  s h o ul d t h e y b e  n ec ess ar y,  will  b e  el a b or at e d,  
wit h  acc o m p a n yi n g  r ati o n al e f or e ac h.  T his  will  b e  r e p ort e d t o s p o ns or, I R B a n d  
m a n uf act ur ers  w h o  will  d o n at e  t h e st u d y dr u g  ( S hir e P h ar m ac e utic als  Gr o u p  plc.)
Dr.  A dl er  will  pr o vi d e  Dr.  T h a k k ar  ( m e dic al m o nit or)  i nfor m ati o n  o n  a  m o nt hl y  b asis  f or 
t h e m e dic al  m o nit or  r e p ort. T h e  m e dic al  m o nit ors  r e p ort will  b e  s u b mitt e d t o t h e I R B at  
e ac h  c o nti n u ati o n. U nl ess,  t h er e ar e  s eri o us a d v ers e  e v e nts  a n d  t h os e will  b e  r e p ort e d 
i m m e di at el y D at a  M o nit ori n g  C o m mitt e e-  N ot  R e q uir e d
9
D at a  H a n dli n g  a n d  R e c o r d  K e e pi n g
9. 1
C o nfi d e nti alit y
A n y  i d e ntif yi n g i nf or m ati o n c oll ect e d i n t h e c o urs e of  t h e st u d y, s uc h as  st u d y r ec or ds a n d  
e v al u ati o ns  (i ncl u di n g t hos e  st or e d o n  c o m p ut er), will b e  s ec ur el y l oc k e d a n d  will  o nl y  b e  
acc essi bl e  t o a ut h ori z e d  st u d y st aff. If t h e r es ults of  t his st u d y ar e  r e p ort e d i n m e dic al  
j o ur n als or  at  m e eti n gs,  t h e p artici p a nt  will n ot  b e  i d e ntifi e d b y n a m e  or  ot h er  i d e ntif yi n g 
i nf or m ati o n.
9. 2
C o nfi d e nti alit y  a n d  HI P A A
I nf or m ati o n a b o ut  st u d y s u bj ects will  b e  k e pt  c o nfi d e nti al a n d  m a n a g e d  acc or di n g  t o t h e 
r e q uir e m e nts of  t h e H e alt h  I ns ur a nc e P ort a bilit y  a n d  Acc o u nt a bilit y  Act  of  1 9 9 6  ( HI P A A). 
T h os e  r e g ul ati o ns r e q uir e a  si g n e d s u bj ect a ut h oriz ati o n  i nf or mi n g t h e s u bj ect of  t h e 
f oll o wi n g:
P a g e 4 5


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6

W h at  pr ot ect e d  h e alt h  i nf or m ati o n ( P HI) will  b e  c oll ect e d fr o m s u bj ects i n t his 
st u d y.

W h o  will  h a v e  acc ess  t o t h at i nf or m ati o n a n d  w h y.

W h o  will  us e  or  discl os e  t h at i nf or m ati o n.

T h e ri g hts of a r es e arc h s u bj ect t o r e v o k e t h eir a ut h ori z ati o n f or us e of t h eir P HI.
I n t h e e v e nt t h at a s u bj ect r e v o k es a ut h ori z ati o n t o c oll ect or us e P HI, t h e i n v esti g at or, b y 
r e g ul ati o n, r et ai ns t h e a bilit y t o us e all i nf or m ati o n c oll ect e d pri or t o t h e r e v oc ati o n of 
s u bj ect a ut h ori z ati o n. F or s u bj ects t h at h a v e r e v o k e d a ut h ori z ati o n t o c oll ect or us e P HI, 
att e m pts s h o ul d b e m a d e t o o bt ai n p er missi o n t o c oll ect at l e ast vit al st at us (i. e. t h at t h e 
s u bj ect is ali v e) at t h e e n d of t h eir sc h e d ul e d st u d y p eri o d.
9. 3
S o u r c e  D o c u m e nt s
S o urc e  d at a  is all  i nf or m ati o n, ori gi n al  r ec or ds of  cli nic al fi n di n gs, o bs er v ati o ns,  or  ot h er  
acti viti es  i n a  cli nic al tri al n ec ess ar y  f or t h e r ec o nstr ucti o n a n d  e v al u ati o n  of t h e  tri al.
S o urc e  d at a  ar e  c o nt ai n e d i n s o urc e d oc u m e nts.  E x a m pl es  of  t h es e ori gi n al  d oc u m e nts,  a n d  
d at a  r ec or ds i ncl u d e: h os pit al r ec or ds, cli nic al a n d  offic e  c h arts, l a b or at or y n ot es,  
m e m or a n d a,  s u bj ects’ di ari es  or  e v al u ati o n  c h ec klists, p h ar m ac y  dis p e nsi n g  r ec or ds, 
r ec or d e d d at a  fr o m a ut o m at e d  i nstr u m e nts, c o pi es or  tr a nscri pti o ns c ertifi e d aft er  
v erific ati o n  as  b ei n g  acc ur at e  a n d  c o m pl et e, micr ofic h es,  p h ot o gr a p hic  n e g ati v es,  micr ofil m  
or  m a g n etic  m e di a,  x-r a ys,  s u bj ect fil es, a n d  r ec or ds k e pt  at  t h e p h ar m ac y,  at  t h e 
l a b or at ori es, a n d  at  m e dic o-t ec h nic al  d e p art m e nts  i n v ol v e d i n t h e cli nic al tri al.
9. 4
C a s e R e p o rt  F o r m s
T h e  st u d y c as e r e p ort f or m ( C R F) is t h e pri m ar y  d at a  c oll ecti o n i nstr u m e nt f or t h e st u d y.  
All  d at a  r e q u est e d o n  t h e C R F  m ust b e  r ec or d e d. All  missi n g  d at a  m ust  b e  e x pl ai n e d.  If a 
s p ac e o n  t h e C R F  is l eft bl a n k  b ec a us e  t h e pr oc e d ur e  w as  n ot  d o n e  or  t h e q u esti o n  w as  n ot  
as k e d,  writ e “ N / D”.  If t h e it e m is n ot  a p plic a bl e  t o t h e i n di vi d u al c as e, writ e  “ N / A”. All  
e ntri es  s h o ul d b e pri nt e d  l e gi bl y i n bl ac k  i n k. If a n y  e ntr y  err or  h as  b e e n  m a d e,  t o c orr ect 
s uc h a n  err or,  dr a w  a  si n gl e str ai g ht li n e t hr o u g h t h e i nc orr ect e ntr y  a n d  e nt er  t h e c orr ect 
d at a  a b o v e  it. All  s uc h c h a n g es m ust b e  i niti al e d a n d  d at e d.  D O  N O T  E R A S E O R  W HI T E  
O U T  E R R O R S.  F or  cl arific ati o n of  ill e gi bl e or  u nc ert ai n  e ntri es,  pri nt  t h e cl arific ati o n a b o v e 
P a g e 4 6


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
t h e it e m, t h e n i niti al a n d d at e it.  
9. 5
R e c o r d s  R et e nti o n
It is t h e i n v esti g at or’s r es p o nsi bilit y t o r et ai n st u d y ess e nti al  d oc u m e nts  f or at  l e ast 2  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  i n t h eir c o u ntr y a n d u ntil  t h er e ar e  n o  
p e n di n g  or  c o nt e m pl at e d m ar k eti n g  a p plic ati o ns  i n t h eir c o u ntr y or at  l e ast 2  y e ars  h a v e  
el a ps e d  si nc e t h e 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 n v 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  if r e q uir e d b y  a n  
a gr e e m e nt  wit h  t h e s p o ns or. I n s uc h a n  i nst a nc e, it is t h e r es p o nsi bilit y of  t h e s p o ns or t o 
i nf or m t h e i n v esti g at or /i nstit uti o n as  t o w h e n  t h es e d oc u m e nts  n o  l o n g er n e e d  t o b e  
r et ai n e d.
1 0
St u d y  M o nit o ri n g,  A u diti n g,  a n d  I n s p e cti n g
1 0. 1 St u d y  M o nit o ri n g  Pl a n
T his  st u d y will  b e  m o nit or e d  acc or di n g t o  t h e m o nit o ri n g  pl a n  i n Att ac h m e nt  [ 6]. T h e  
i n v esti g at or will  all oc at e  a d e q u at e  ti m e f or s uc h m o nit ori n g acti viti es.  T h e  I n v esti g at or 
will  als o  e ns ur e  t h at t h e m o nit or  or  ot h er  c o m pli a nc e or  q u alit y ass ur a nc e  r e vi e w er is 
gi v e n  acc ess  t o all  t h e a b o v e  n ot e d  st u d y-r el at e d d oc u m e nts  a n d  st u d y r el at e d f aciliti es 
( e. g. p h ar m ac y,  di a g n ostic  l a b or at or y, etc.),  a n d  h as  a d e q u at e  s p ac e t o c o n d uct t h e 
m o nit ori n g  visit.
1 0. 2 A u diti n g  a n d  I n s p e cti n g
T h e  i n v esti g at or will  p er mit  st u d y-r el at e d m o nit ori n g,  a u di ts, a n d  i ns p ecti o ns b y  t h e 
I R B / E C, t h e s p o ns or, g o v er n m e nt  r e g ul at or y b o di es,  a n d  U ni v ersit y  c o m pli a nc e a n d  q u alit y  
ass ur a nc e  gr o u ps  of  all  st u d y r el at e d d oc u m e nts  ( e. g., s o urc e d oc u m e nts, r e g ul at or y  
d oc u m e nts,  d at a  c oll ecti o n i nstr u m e nts, st u d y d at a  etc.).  T h e  i n v esti g at or will  e ns ur e  t h e 
c a p a bilit y f or i ns p ecti o ns of  a p plic a bl e  st u d y-r el at e d f aciliti es ( e. g., p h ar m ac y,  di a g n ostic  
l a b or at or y, etc.).
P artici p ati o n  as  a n  i n v esti g at or i n t his st u d y i m pli es acc e pt a nc e of  p ot e nti al  i ns p ecti o n b y  
g o v er n m e nt  r e g ul at or y a ut h oriti es  a n d  a p plic a bl e  U ni v ersit y  c o m pli a nc e a n d  q u alit y  
ass ur a nc e  offic es.
P a g e 4 7


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1 1
Et hi c al  C o n si d e r ati o n s
T his  st u d y is t o b e  c o n d uct e d acc or d a nc e  wit h a p plic a bl e  U S  g o v er n m e nt  r e g ul ati o ns a n d  
i nt er n ati o n al st a n d ar ds of  G o o d  Cli nic al  Pr actic e,  a n d  a p plic a bl e  i nstit uti o n al r es e arc h 
p olici es  a n d  pr oc e d ur es.
T his  pr ot oc ol  a n d a n y  a m e n d m e nts  will  b e  s u b mitt e d t o a  pr o p erl y  c o nstit ut e d  
I nstit uti o n al R e vi e w  B o ar d  (I R B) or  i n d e p e n d e nt Et hics  C o m mitt e e  ( E C) i n a gr e e m e nt  wit h  
l oc al l e g al pr escri pti o ns,  f or f or m al a p pr o v al  of  t h e st u d y c o n d uct. T h e d ecisi o n  of  t h e 
I R B / E C c o nc er ni n g t h e c o n d uct of  t h e st u d y will  b e  m a d e  i n writi n g  t o t h e i n v esti g at or a n d  
a  c o p y of  t his d ecisi o n  will  b e  pr o vi d e d  t o t h e s p o ns or b ef or e  c o m m e nc e m e nt of  t his st u d y. 
T h e  i n v esti g at or s h o ul d pr o vi d e  a  list of  I R B / E C m e m b ers  a n d  t h eir affili at e  t o t h e s p o ns or.
All  s u bj ects f or t his st u d y will  b e  pr o vi d e d  a  co ns e nt  f or m d escri bi n g  t his st u d y a n d  
pr o vi di n g  s uffici e nt i nf or m ati o n f or s u bj ects t o m a k e  a n  i nf or m e d d ecisi o n  a b o ut  t h eir 
p artici p ati o n  i n t his st u d y. S e e  Att ac h m e nt  [ 2] f or a  c o p y of  t h e S u bj ect  I nf or m e d C o ns e nt  
F or m.  T his  c o ns e nt f or m will  b e  s u b mitt e d wit h  t h e pr ot oc ol  f or r e vi e w a n d  a p pr o v al  b y  
t h e I R B / E C f or t h e st u d y. T h e  f or m al c o ns e nt of  a  s u bj ect, usi n g  t h e I R B / E C- a p pr o v e d 
c o ns e nt f or m, m ust  b e  o bt ai n e d  b ef or e  t h at s u bj ect u n d er g o es  a n y  st u d y pr oc e d ur e.  T h e  
c o ns e nt f or m m ust  b e  si g n e d b y  t h e s u bj ect a n d  t h e i n v esti g at or- d esi g n at e d r es e arc h 
pr of essi o n al  o bt ai ni n g  t h e c o ns e nt.
R es e arc h  c o or di n at or will  o bt ai n  c o ns e nt as  n ot e d  i n t h e st a n d ar d o p er ati n g  pr oc e d ur e  f or 
t h e c o ns e nt pr oc ess.  S e e  Att ac h m e nt  [ 1]
It will  n ot  b e  n ec ess ar y  t o us e  ‘ A u dit or / Wit n ess’ a n d / or  tr a nsl at or b ec a us e  p ers o ns  w h o  
c o ns e nt m ust  b e  a bl e  t o r e a d E n glis h  w ell  e n o u g h  t o u n d erst a n d  i nf or m e d c o ns e nt a n d  
st u d y m at eri als.  P ati e nt  m ust  b e  a bl e  t o p ass  t h e s h ort q uiz  gi v e n  at t h e  e n d  of  t h e c o ns e nt 
pri or  t o si g ni n g c o ns e nt.
1 2
St u d y  Fi n a n c e s
1 2. 1 F u n di n g  S o urc e
T his  st u d y is fi n a nc e d t hr o u g h a  gr a nt  fr o m S hir e  P h ar m a.
P a g e 4 8


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
1 2. 2 C o nfli ct  of  I nt e r e st
Dr.  A dl er,  w h o  h as  a  co nflict  of  i nt er est wit h  t his st u d y ( p at e nt o w n ers hi p,  r o y alti es, or  
fi n a nci al g ai n gr e at er  t h a n t h e mi ni m u m  all o w a bl e  b y  t h eir i nstit uti o n, etc.)  h a d  t h e c o nflict 
r e vi e w e d b y  a  pr o p erl y  c o nstit ut e d C o nflict  of  I nt er est C o m mitt e e  wit h  a  C o m mitt e e-  
s a ncti o n e d c o nflict m a n a g e m e nt  pl a n t h at  h as  b e e n  r e vi e w e d a n d  a p pr o v e d  b y  t h e st u d y 
s p o ns or pri or  t o p artici p ati o n  i n t his st u d y. All  N Y U L M C  i n v esti g at ors will f oll o w t h e 
a p plic a bl e  U ni v ersit y  c o nflict of  i nt er est p olici es.
1 2. 3 S u bj e ct  Sti p e n d s  o r  P a y m e nt s
P ati e nts  will  n ot  b e  p ai d  f or p artici p ati o n  i n t his st u d y. T h e y will r ec ei v e  a  t w ent y  fi v e  
d oll ar  v o uc h er  f or t h eir tr a v el at  e ac h  st u d y visit.  B y  t h e e n d  of  t h e st u d y t h e p ati e nt  w o ul d  
h a v e  r ec ei v e d a  c o m bi n e d a m o u nt  of  t hr e e h u n dr e d  d oll ars  f or tr a v el. W e  will  gi v e  p ati e nts  
v o uc h ers  w hic h  t h e y w o ul d  r e d e e m f or c as h at  e ac h  att e n d e d  visit.
1 3
P u bli c ati o n  Pl a n
N eit h er  t h e c o m pl et e n or  a n y  p art  of  t h e r es ults of  t h e st u d y c arri e d o ut u n d er  t his   
pr ot oc ol,  n or  a n y  of  t h e i nf or m ati o n pr o vi d e d  b y  t h e s p o ns or f or t h e p ur p os es  of   
p erf or mi n g  t h e st u d y, will  b e  p u blis h e d  or  p ass e d  o n  t o a n y  t hir d p art y  wit h o ut  t h e c o ns e nt 
of  t h e st u d y s p o ns or. A n y  i n v esti g at or i n v ol v e d wit h  t his st u d y is o bli g at e d  t o pr o vi d e  t h e 
s p o ns or wit h  c o m pl et e t est r es ults a n d  all  d at a  d eri v e d  fr o m t h e st u d y.
1 4
R ef e r e n c e s
[ 1] K essl er,  R.  C.,  A dl er,  L.,  B ar kl e y,  R.,  Bi e d er m a n,  J., C o n n ers,  C.  K.,  D e ml er,  O.,  …  Z as l a vs k y,
A.  M.  ( 2 0 0 6). T h e  pr e v al e nc e  a n d  c orr el at es of  a d ult  A D H D  i n t h e U nit e d  St at es:  
r es ults fr o m t h e N ati o n al  C o m or bi dit y S ur v e y  R e plic ati o n.  T h e  A m eric a n  J o ur n al of  
Ps yc hi atr y , 1 6 3 ( 4), 7 1 6 – 7 2 3
[ 2] Bi e d er m a n,  J., &  F ar a o n e,  S.  V.  ( 2 0 0 5). Att e nti o n- d eficit  h y p er acti vit y  dis or d er.  L a nc et , 
3 6 6 ( 9 4 8 1), 2 3 7 – 2 4 8.
P a g e 4 9


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
[ 3] Wil e ns,  T.  E.,  &  D o ds o n,  W.  ( 2 0 0 4). A  cli nic al p ers p ecti v e  of  att e nti o n-  
d eficit / h y p er acti vit y  dis or d er  i nt o a d ult h o o d. T h e  J o ur n al of  Cli nic al  Ps yc hi atr y , 
6 5 ( 1 0), 1 3 0 1 – 1 3 1 3.
[ 4] S ol a nt o,  M.  V.  ( 2 0 0 2). D o p a mi n e  d ysf u ncti o n  i n A D / H D:  i nt egr ati n g  cli nic al a n d  b asic  
n e ur osci e nc e  r es e arc h. B e h a vi or al  Br ai n  R es e arc h , 1 3 0 ( 1- 2), 6 5 – 7 1.
[ 5] Bi e d er m a n,  J., &  S p e nc er,  T.  ( 1 9 9 9). Att e nti o n- d eficit / h y p er acti vit y  dis or d er  ( A D H D) as  
a  n or a dr e n er gic  dis or d er.  Bi ol o gic al  Ps yc hi atr y , 4 6 ( 9), 1 2 3 4 – 1 2 4 2.
[ 6] B ar kl e y,  R. A.  ( 2 0 0 6). Att e nti o n- D eficit H y p er acti vit y  Dis or d er:  A  H a n d b o o k  f or Di a g n osis 
a n d  Tr e at m e nt  ( 3r d e diti o n).  N e w  Y or k:  T h e  G uilf or d  Pr ess.
[ 7] B ar kl e y,  R.  A.  (2 0 1 2).  Disti n g uis hi n g  sl u g gis h c o g niti v e t e m p o fr o m att e nti o n-  
d eficit / h y p er acti vit y  dis or d er  i n a d ults. J o ur n al of  A b n or m al  Ps yc h ol o g y , 1 2 1 ( 4), 
9 7 8 – 9 9 0.
[ 8] B ar kl e y,  R.  A.  (2 0 1 2).  B ar kl e y  A d ult  A D H D  R ati n g  Sc al e--I V . N e w  Y or k:  T h e  G uilf or d  
Pr ess.
[ 9] S ol a nt o,  M.  V.,  A bi k off,  H.,  S o n u g a- B ar k e,  E.,  Sc h ac h ar,  R.,  L o g a n,  G.  D.,  Wi g al,  T., …  
T ur k el,  E.  ( 2 0 0 1). T h e  ec ol o gic al v ali dit y  of  d el a y  a v ersi o n  a n d  r es p o ns e i n hi biti o n 
as  m e as ur es  of  i m p ulsi vit y i n A D / H D:  a  s u p pl e m e nt t o t h e NI M H  m ulti m o d al  
tr e at m e nt st u d y of  A D / H D.  J o ur n al of  A b n or m al  C hil d  Ps yc h ol o g y , 2 9 ( 3), 2 1 5 – 2 2 8.
[ 1 0] V y v a ns e  ( 2 0 1 2) [ p ac k a g e i ns ert]. W a y n e,  P A:  S hir e  U S  I N C.
[ 1 1] C ast ell a n os,  F. X.,  &  T a n n o c k, R.  ( 2 0 0 2). N e ur osci e nc e  of  att e nti o n-  
d eficit / h y p er acti vit y  dis or d er:  t h e s e arc h f or e n d o p h e n ot y p es.  N at ur e  R e vi e ws.  
N e ur osci e nc e , 3 ( 8), 6 1 7 – 6 2 8.
P a g e 5 0


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
[ 1 2] Ni g g,  J. T.  ( 2 0 0 5). N e ur o ps yc h ol o gic  t h e or y a n d  fi n di n gs i n att e nti o n-  
d eficit / h y p er acti vit y  dis or d er: t h e  st at e of  t h e fi el d a n d  s ali e nt c h all e n g es f or t h e 
c o mi n g d ec a d e.  Bi ol o gic al  Ps yc hi atr y , 5 7 ( 1 1).
[ 1 3] S o n u g a- B ar k e,  E.  J. S.  ( 2 0 0 5). C a us al  m o d els  of  att e nti o n- d eficit / h y p er acti vit y  
dis or d er:  fr o m c o m m o n si m pl e d eficits  t o m ulti pl e  de v el o p m e nt al  p at h w a ys.  
Bi ol o gic al  Ps yc hi atr y , 5 7 ( 1 1), 1 2 3 1 – 1 2 3 8.
[ 1 4] S er g e a nt,  J. A.  ( 20 0 5).  M o d eli n g  att e nti o n- d eficit / h y p er acti vit y  dis or d er: a  critic al 
a p pr ais al  of  t h e c o g niti v e- e n er g etic m o d el.  Bi ol o gic al  Ps yc hi atr y , 5 7 ( 1 1), 1 2 4 8 –  
1 2 5 5.
[ 1 5] S o n u g a- B ar k e,  E.,  Bits a k o u,  P.,  &  T h o m ps o n,  M.  ( 2 0 1 0). B e y o n d  t h e d u al  p at h w a y  
m o d el:  e vi d e nc e  f or t h e diss oci ati o n  of  ti mi n g, i n hi bit or y, a n d  d el a y-r el at e d  
i m p air m e nts i n att e nti o n- d eficit / h y p er acti vit y  dis or d er.  J o ur n al of  t h e A m eric a n  
Ac a d e m y  of  C hil d a n d  A d ol esc e nt  Ps yc hi atr y , 4 9 ( 4), 3 4 5 – 3 5 5.
[ 1 6] L u d wi g,  H.  T.,  M att e,  B.,  K atz,  B.,  &  R o h d e,  L.  A.  ( 2 0 0 9). D o sl u g gis h c o g niti v e t e m p o 
s y m pt o ms pr e dict  r es p o ns e t o m et h yl p h e ni d at e  i n p ati e nts  wit h  att e nti o n-  
d eficit / h y p er acti vit y  dis or d er-i n att e nti v e  t y p e? J o ur n al of C hil d  a n d  A d ol esc e nt  
Ps yc h o p h ar m ac ol o g y , 1 9 ( 4), 4 6 1 – 4 6 5.
[ 1 7] A dl er,  L.,  &  C o h e n,  J. ( 2 0 0 4). Di a g n osis  a n d  e v al u ati o n  of  a d ults  wit h  att e nti o n-  
d eficit / h y p er acti vit y  dis or d er.  T h e  Ps yc hi atric  Cli nics  of  N ort h  A m eric a , 2 7 ( 2), 1 8 7 –  
2 0 1.
[ 1 8] R ot h  R M,  Is q uit h P K,  Gi oi a  G A  ( 2 0 0 5) B e h a vi or  R ati n g  I n v e nt or y of  E x ec uti v e  
F u ncti o n – A d ult  V ersi o n  ( B RI E F- A). L utz,  F L:  Ps yc h ol o gic al  Ass ess m e nt  R es o urc es.
P a g e 5 1


C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
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C O N FI D E N TI A L
T hi s m at eri al  i s t h e pr o p ert y of t h e N Y U S c h o ol of  M e di ci n e a n d  L a n g o n e  M e di c al C e nt er.  D o  n ot di s cl o s e or u s e  e x c e pt a s  
a ut h ori z e d i n  writi n g  b y t h e  st u d y s p o n s or
[ S HI R E S C T  s 1 3- 0 1 2 8 8]
V er si o n:  0 3/ 0 3/ 2 0 1 6
A m eric a n  S oci et y  of  H e alt h- S yst e m  P h ar m acists,  I nc. R etr ei v e d  J u n e 3,  2 0 1 4  fr o m: 
htt p: / / w w w. nl m. ni h. g o v / m e dli n e pl us / dr u gi nf o / m e ds / a 6 0 7 0 4 7. ht ml
[ 2 7] C a m bri d g e  C o g niti o n.  ( 2 0 1 4). R etri e v e d  J u n e 3,  2 0 1 4  fr o m: 
htt p: / / w w w.c a m bri d g ec o g niti o n.c o m
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R etri e v e d  J u n e 3,  2 0 1 4,  fr o m:  
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