A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate an Alternative Injection Paradigm for OnabotulinumtoxinA (BOTOX®) in the Treatment of Overactive Bladder in Patients With Urinary Incontinence (LO-BOT)
Phase: PHASE4
Conditions: Urinary Bladder, Overactive, Urinary Incontinence
Sponsor: Allergan

NCT03052764 
 
Study ID: CMO‐US‐URO‐0470 
 
 
 
Title: A Multicenter, Randomized, Double‐Blind, Placebo‐Controlled, Parallel‐Group Study to 
Evaluate an Alternative Injection Paradigm for OnabotulinumtoxinA (BOTOX®) in the 
Treatment of Overactive Bladder in Patients with Urinary Incontinence (LO‐BOT). 
 
Protocol Amendment 1: 08 May 2018 
 
 
 

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Protocol Summary 
 
Study Compound(s): */*3W*E89FKLC@ELDKFO@E+LI@=@<;)<LIFKFO@EFDGC<O
Phase:  IV
Study Objective(s): /F<M8CL8K<K?<<==@:8:P8E;J8=<KPF=*/*30FE89FKLC@ELDKFO@E:FDG8I<;KF
GC8:<9FN?<E@EA<:K<;@EKFK?<9C8;;<ILJ@E>8E8CK<IE8K@M<@EA<:K@FEG8I8;@>DKI@>FE8C8E;G<I@	KI@>FE8C
@EA<:K@FEJ@EI<;L:@E>K?<ELD9<IF=;8@CPLI@E8IP@E:FEK@E<E:<<G@JF;<J@EG8K@<EKJN@K?FM<I8:K@M<9C8;;<I
*8E;LI@E8IP@E:FEK@E<E:<N?FJ<JPDGKFDJ?8M<EFK9<<E8;<HL8K<CPD8E8><;N@K?8E8EK@:?FC@E<I>@:

Key Clinical Hypotheses
 
*/*30@JDFI<<==<:K@M<:FDG8I<;KFGC8:<9FN?<E@EA<:K<;@EKFK?<9C8;;<ILJ@E>K?<
8CK<IE8K@M<G8I8;@>DKI@>FE8C8E;G<I@	KI@>FE8C@EA<:K@FEJ@EI<;L:@E>K?<ELD9<IF=;8@CPLI@E8IP
@E:FEK@E<E:<<G@JF;<J=IFD98J<C@E<8K2<<B

 
*/*30?8J8E8::<GK89C<9<KK<IJ8=<KPGIF=@C<@E:CL;@E>K?<I@JBF=@E:FDGC<K<9C8;;<I
<DGKP@E>8E;E<<;=FI:C<8E@EK<ID@KK<EK:8K?<K<I@Q8K@FE$N?<E8;D@E@JK<I<;8J@EA<:K@FEJ@EKF
K?<CFN<IG8IKF=K?<9C8;;<IKI@>FE8C8E;G<I@	KI@>FE8CF=G8K@<EKJN@K?*N@K?LI@E8IP
@E:FEK@E<E:<

Study Design 
Structure(LCK@:<EK<II8E;FD@Q<;;FL9C<	9C@E;GC8:<9F	:FEKIFCC<;G8I8CC<C	>IFLG
Duration+8K@<EKJN@CCG8IK@:@G8K<@EK?<JKL;PLEK@CK?<=FCCFN@E>JKL;P<O@K:I@K<I@88I<D<K
 
FDGC<K@FEF=N<<BJGFJK-8E;FD@Q8K@FE8P8E;
 
$=8J<:FE;@EA<:K@FEN8JI<:<@M<;8KC<8JKN<<BJGFJK	KI<8KD<EK=FCCFN	LG8=K<I/I<8KD<EK

/?<I<=FI<=FI=LCCJKL;PG8IK@:@G8K@FEG8K@<EKJN@CC9<<OG<:K<;KFG8IK@:@G8K<@EK?<JKL;P=FI8D@E@DLD
;LI8K@FEF=N<<BJ@<@=G8K@<EKHL8C@=@<J=FIJ<:FE;KI<8KD<EK8K2<<B:C@E@:M@J@K8E;GIF:<<;JKFJ<:FE;
KI<8KD<EK8E;8D8O@DLD;LI8K@FEF=8GGIFO@D8K<CPN<<BJ@<@=8G8K@<EKI<HL<JK<;8E;HL8C@=@<;=FI
/I<8KD<EK8K2<<BI<:<@M<;8E@EA<:K@FE8K2<<B8E;:FDGC<K<JFK?<IJKL;PM@J@KJ8KK?<D8O@DLD
8CCFN89C<M@J@KN@E;FN

Study Treatment Group*/*30$EA<:K@FE 
Control+C8:<9FJ8C@E<$EA<:K@FE
Dosage/Dose RegimenCCG8K@<EKJN@CCI<:<@M<8JKL;PKI<8KD<EKFE8P=FCCFN@E>=LC=@CCD<EKF=8CCF=K?<
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JG<:@=@<;HL8C@=@:8K@FE=FI/I<8KD<EK:I@K<I@88E;8PF=/I<8KD<EKI@K<I@8


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D'@EKFK?<CFN<I
GFIK@FEF=K?<GFJK<I@FIN8CCF=K?<9C8;;<I8E;@EKFK?<KI@>FE<M@8:PJKFJ:FGP


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Treatment 1: 
CC<C@>@9C<G8K@<EKJN?FD<<K@E:CLJ@FE<O:CLJ@FE:I@K<I@8N@CCI<:<@M<K?<@I=@IJKKI<8KD<EKN@K?
*/*30FIGC8:<9F8=K<II8E;FD@Q8K@FEFE8P
CC8PF=/I<8KD<EKI@K<I@8DLJK9<
=LC=@CC<;GI@FIKFK?<@EA<:K@FEGIF:<;LI<

8PF=/I<8KD<EKI@K<I@8
 
<EKI8CC89FI8KFIPLI@E8CPJ@JI<JLCKJ8E;@=8GGC@:89C<LI@E<:LCKLI<8E;J<EJ@K@M@KPI<JLCKJ
=FIGFJJ@9C<LI@E8IPKI8:K@E=<:K@FE0/$=IFD.:I<<E@E>?8M<9<<EI<M@<N<;
 
)<>8K@M<LI@E<;@GJK@:BI<8><EKJKI@GK<JK=FIE@KI@K<J8E;C<LBF:PK<<JK<I8J<2FE
K?<;8PF=/I<8KD<EK

 
+8K@<EK@J8JPDGKFD8K@:=FI80/$FEK?<;8PF=KI<8KD<EK@EK?<FG@E@FEF=K?<
@EM<JK@>8KFI

 
+8K@<EK?8J;@J:FEK@EL<;8EP8EK@GC8K<C<KFI8EK@:F8>LC8EKK?<I8GPFID<;@:8K@FEJN@K?
8EK@:F8>LC8K@M<<==<:KJ;8PJGI@FIKFKI<8KD<EK
.FD<D<;@:8K@FEJD8PE<<;KF9<
N@K??<C;=FI;8PJG<I:C@E@:8CAL;>D<EKF=K?<@EM<JK@>8KFI

 
)<>8K@M<LI@E<GI<>E8E:PK<JK=FINFD<EF=:?@C;9<8I@E>GFK<EK@8CFEK?<;8PF=
/I<8KD<EK

 
+8K@<EK?8J@E@K@8K<;8GGIFGI@8K<8EK@9@FK@:D<;@:8K@FE8GGIFO@D8K<CP?FLIJKF
;8PJGI@FIKFKI<8KD<EK@EA<:K@FE8E;N@CC:FEK@EL<@KFEK?<;8PF=KI<8KD<EK@EA<:K@FE
8E;=FIKF;8PJ8=K<IKI<8KD<EK@EA<:K@FEJ<<.<:K@FE

+IFG?PC8:K@:EK@9@FK@:J
 
)FJPDGKFDJFI?@JKFIPF=9C8;;<IJKFE<JFI9C8;;<ID8C@>E8E:@<J98J<;FE:C@E@:8C
8JJ<JJD<EK
 
$EM<JK@>8KFI;<<DJJKL;PKI<8KD<EK@JD<;@:8CCP8GGIFGI@8K<8E;EF:FE;@K@FEFIJ@KL8K@FE
<O@JKJN?@:?@EK?<@EM<JK@>8KFISJFG@E@FEGLKJK?<G8K@<EK8KJ@>E@=@:8EKI@JB=IFD
I<:<@M@E>JKL;PKI<8KD<EK

Treatment 2: 
J<:FE;KI<8KD<EKD8P9<8;D@E@JK<I<;GIFM@;<;K?<G8K@<EKHL8C@=@<J=FI/I<8KD<EKJ<<9<CFN
:I@K<I@88E;FECP@=K?<8PF=/I<8KD<EKI@K<I@88I<=LC=@CC<;
CCG8K@<EKJN@CCI<:<@M<*/*3
0=FIK?<@IJ<:FE;KI<8KD<EK
/?<,L8C@=@:8K@FE=FI/I<8KD<EK:8EF::LI8EPK@D<JK8IK@E>8K
2<<BLGKF2<<BGFJK/I<8KD<EK8E;DLJKF::LI;LI@E>8:C@E@:M@J@K<@K?<I8K8I<>LC8I
GI<J:?<;LC<;M@J@KFI8E8;;@K@FE8CLEJ:?<;LC<;M@J@K;<G<E;@E>FEK?<K@D@E>F=K?<I<HL<JK=FI8
J<:FE;KI<8KD<EK
$=K?<G8K@<EK;F<JEFKI<HL<JK8J<:FE;KI<8KD<EKK?<EK?<2<<B:C@E@:M@J@KN@CC
9<8E<O@KM@J@K

,L8C@=@:8K@FE=FI/I<8KD<EK:I@K<I@8
 
+8K@<EKDLJK@E@K@8K<I<HL<JK=FI/I<8KD<EK

 
+8K@<EK<OG<I@<E:<J≥<G@JF;<JF=LI@E8IPLI><E:P@E:FEK@E<E:<N@K?EFDFI<K?8EFE<
LI><E:P@E:FEK@E<E:<	=I<<;8P8J;<K<ID@E<;9P:FEJ<:LK@M<;8PJF=9C8;;<I;@8IP
:FDGC<K@FE@EK?<N<<BGI@FIKFK?<,L8C@=@:8K@FE=FI/I<8KD<EKM@J@K


CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P


 
+FJK	MF@;I<J@;L8C+1-LI@E<MFCLD<DLJK9<D'8KK?<,L8C@=@:8K@FE=FI
/I<8KD<EKM@J@K

 
$EM<JK@>8KFI;<<DJK?8K/I<8KD<EK@JD<;@:8CCP8GGIFGI@8K<8E;EF:FE;@K@FEFI
J@KL8K@FE<O@JKJN?@:?@EK?<@EM<JK@>8KFISJFG@E@FEGLKJK?<G8K@<EK8KJ@>E@=@:8EKI@JB
=IFDI<:<@M@E>8J<:FE;KI<8KD<EK

 
D@E@DLDF=N<<BJDLJK?8M<<C8GJ<;J@E:</KI<8KD<EK

*E:<K?<J<:I@K<I@8?8M<9<<ED<KK?<G8K@<EKN@CC9<:FEJ@;<I<;HL8C@=@<;=FI/I<8KD<EK

/I<8KD<EK8;D@E@JKI8K@FEJ?FLC;F::LIN@K?@E;8PJF=K?<,L8C@=@:8K@FE=FI/I<8KD<EKM@J@K
/?<
GI<M@FLJCP;<J:I@9<;8PF=/I<8KD<EK:I@K<I@8DLJK9<D<K8KK?</I<8KD<EKM@J@KGI@FIKF@EA<:K@FE

Randomization:
!FCCFN@E>K?<J:I<<E@E>G<I@F;G8K@<EKJN?FD<<KK?<JKL;P@E:CLJ@FE<O:CLJ@FE:I@K<I@8N@CC9<I8E;FDCP
8JJ@>E<;9P8E@EK<I8:K@M<N<9I<JGFEJ<JPJK<D$2-.KFF=KI<8KD<EK8IDJ*/*30FIGC8:<9F
@E8I8K@F
*E<I8E;FD@Q8K@FEELD9<IN@CC9<8JJ@>E<;KF<8:?G8K@<EKGI@FIKFK?<=@IJKKI<8KD<EK8E;N@CC9<
8JJF:@8K<;N@K?FE<F=K?<=FCCFN@E>KI<8KD<EK8IDJ
 */*30
 +C8:<9F

CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P



CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P


Study Population Characteristics 
Number of Patients or SubjectsKC<8JKG8K@<EKJN@CC9<I8E;FD@Q<;8K8GGIFO@D8K<CPJ@K<J@EK?<
0E@K<;.K8K<J0.@EFI;<IKF8:?@<M<G8K@<EKJ@EK?<*/*30KI<8KD<EK>IFLG8E;G8K@<EKJ@EK?<
GC8:<9FKI<8KD<EK>IFLG8KK?<GI@D8IPK@D<GF@EK@<G8K@<EKJ8K2<<B8I<I<HL@I<;
KC<8JKG8K@<EKJ
N@CC9<I8E;FD@Q<;KFK8B<@EKF8::FLEK8E8KKI@K@FEI8K<F=

LanguageCCJKL;PD8K<I@8CJN?<K?<IGI@EK<;FI<C<:KIFE@:@E:CL;@E>@E=FID<;:FEJ<EK=FIDJ<	@8IP
GIFKF:FC8E;8CCG8K@<EK8E;J@K<@E=FID8K@FEN@CC9<@EK?< E>C@J?'8E>L8><
/?<I<8I<EFGC8EJKFKI8EJC8K<
JKL;PD8K<I@8CJ@EKFFK?<IC8E>L8><J

Condition/Disease+8K@<EKJN@K?JPDGKFDJF=*=I<HL<E:P8E;LI><E:P8E;LI@E8IP@E:FEK@E<E:<N?FJ<
JPDGKFDJ?8M<EFK9<<E8;<HL8K<CPD8E8><;N@K?8E8EK@:?FC@E<I>@:

Key Inclusion Criteria/?<G8K@<EKDLJKD<<KK?<=FCCFN@E>B<P:I@K<I@88KJ:I<<E@E>8E;-8E;FD@Q8K@FE8P
@EFI;<IKF9<@E:CL;<;@EK?<JKL;P
/?<J<8I<K?<B<P:I@K<I@8N?@:?;<=@E<K?<GFGLC8K@FEEFK8:FDGC<K<C@JK
F=8CC@E:CLJ@FE:I@K<I@8
 
+8K@<EK@JD8C<FI=<D8C<8><;≥P<8IJFC;

 
+8K@<EKN<@>?J≥B>C9J

 
+8K@<EK?8JJPDGKFDJF=*=I<HL<E:P8E;LI><E:PN@K?LI@E8IP@E:FEK@E<E:<=FI8G<I@F;F=8K
C<8JKDFEK?J@DD<;@8K<CPGI@FIKFJ:I<<E@E>;<K<ID@E<;9P;F:LD<EK<;G8K@<EK?@JKFIP

 
+8K@<EKLE;<IJK8E;JK?8KK?<P8I<EFKKF8CK<IK?<@I:LJKFD8IPC@=<G8KK<IEJ8IFLE;=CL@;:FEJLDGK@FEFI
D@:KLI@K@FEN?@C<G8IK@:@G8K@E>@EK?@JJKL;P


CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P


Key Exclusion Criteria/?<G8K@<EKN@CC9<<O:CL;<;=IFDG8IK@:@G8K@E>@EK?<JKL;P=FI8EPF=K?<=FCCFN@E>
B<P:I@K<I@88JJ<JJ<;;LI@E>K?<J:I<<E@E>G<I@F;8E;-8E;FD@Q8K@FE8PGI@FIKFJKL;PKI<8KD<EK
/?<J<8I<
K?<B<P:I@K<I@8N?@:?;<=@E<K?<GFGLC8K@FEEFK8:FDGC<K<C@JKF=8CC<O:CLJ@FE:I@K<I@8
 
+8K@<EK?8JJPDGKFDJF=*;L<KF8EPBEFNEE<LIFCF>@:8CI<8JFE<>JG@E8C:FI;@EALIPDLCK@GC<
J:C<IFJ@J:<I<9IFM8J:LC8I8::@;<EKCQ?<@D<ISJ;@J<8J<+8IB@EJFESJ;@J<8J<<K:


 
+8K@<EK?8JI<:<@M<;G?8ID8:FCF>@:K?<I8GPKFKI<8KJPDGKFDJF=*@E:CL;@E>EF:KLI@8N@K?@E
;8PJF=K?<JK8IKF=K?<J:I<<E@E>G<I@F;GIF:<;LI<J

 
+8K@<EKLJ<J$FI@E;N<CC@E>:8K?<K<IKFD8E8><LI@E8IP@E:FEK@E<E:<

 
+8K@<EK?8J8	?FLIKFK8CMFCLD<F=LI@E<MF@;<;D':FCC<:K<;FM<I:FEJ<:LK@M<?FLIJ
;LI@E>K?<	;8P9C8;;<I;@8IP:FCC<:K@FEG<I@F;GI@FIKF-8E;FD@Q8K@FE8P

 
+8K@<EK?8J?8;GI<M@FLJFI:LII<EK9FKLC@ELDKFO@EK?<I8GPF=8EPJ<IFKPG<=FI8EPLIFCF>@:8C
:FE;@K@FE

 
+8K@<EK?8J?8;GI<M@FLJFI:LII<EK9FKLC@ELDKFO@EK?<I8GPF=8EPJ<IFKPG<=FI8EPEFE	LIFCF>@:8C
:FE;@K@FEN@K?@EN<<BJGI@FIKF-8E;FD@Q8K@FE8P

 
+8K@<EK?8J?@JKFIPFI<M@;<E:<F=8EPG<CM@:FILIFCF>@:8C89EFID8C@K@<J9C8;;<IJLI><IPFI;@J<8J<
FK?<IK?8E*K?8KD8P8==<:K9C8;;<I=LE:K@FE@E:CL;@E>9LKEFKC@D@K<;KF
 
+8K@<EK?8J<M@;<E:<F=LI<K?I8C8E;FI9C8;;<IFLKC<KF9JKIL:K@FE@EK?<FG@E@FEF=K?<@EM<JK@>8KFI8K
J:I<<E@E>FI-8E;FD@Q8K@FE8P

 
+8K@<EK?8J8+1-LI@E<MFCLD<F=D'8KJ:I<<E@E>
/?<+1-LI@E<MFCLD<D<8JLI<D<EK:8E
9<I<G<8K<;FE:<K?<G8K@<EK@JKF9<<O:CL;<;@=K?<I<G<8K<;D<8JLI<@J89FM<D'


CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P


Response Measures 
Efficacy:   
Primary:  
 
?8E><=IFD98J<C@E<@EELD9<IF=<G@JF;<JF=LI@E8IP@E:FEK@E<E:<8K2<<B8JI<:FI;<;9P
K?<G8K@<EK@EK?<	;8P9C8;;<I;@8IP

Secondary:  
 
+IFGFIK@FEF=G8K@<EKJN?F8:?@<M<I<;L:K@FE@ELI@E8IP@E:FEK@E<E:<<G@JF;<J:FDGC<K<
:FEK@E<E:<=IFD98J<C@E<@<98J<C@E<GI@FIKF/I<8KD<EK
 
?8E><=IFD98J<C@E<@E;8@CP8M<I8><ELD9<IF=D@:KLI@K@FE<G@JF;<J
 
?8E><=IFD98J<C@E<@E;8@CP8M<I8><ELD9<IF=LI><E:P<G@JF;<J
 
?8E><=IFD98J<C@E<@E;8@CP8M<I8><ELD9<IF=EF:KLI@8<G@JF;<J
 
+IFGFIK@FEF=G8K@<EKJN?F?8M<8GFJ@K@M<KI<8KD<EKI<JGFEJ<FEK?</.J:FI<F=<@K?<IFI
I<GI<J<EK@E>R>I<8KCP@DGIFM<;SFIR@DGIFM<;SI<JG<:K@M<CP

Safety:   
 
;M<IJ<<M<EKJ8E;J<I@FLJ8;M<IJ<<M<EKJ. J
 
+?PJ@:8C<O8D@E8K@FE
 
1@K8CJ@>EJ
 
+1-LI@E<MFCLD<9P9C8;;<IJ:8EFILCKI8JFLE;
 
+I<>E8E:PK<JK=FINFD<EF=:?@C;9<8I@E>GFK<EK@8C8KJ:I<<E@E>9<=FI<JKL;PKI<8KD<EKJ8E;8K
JKL;P<O@K
 
0I@E<;@GJK@:BI<8><EKJKI@GK<JK
 
<EKI8CC89FI8KFIPLI@E<8E8CPJ@J
 
0I@E<:LCKLI<8E;J<EJ@K@M@KP
 
FE:FD@K8EKD<;@:8K@FEJ
 
FE:LII<EKGIF:<;LI<J@E:CL;@E>:8K?<K<I@Q8K@FEN@K?8JJF:@8K<;=I<HL<E:P8E;I<8JFE=FI
:8K?<K<I@Q8K@FE


CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P


General Statistical Methods and Types of Analyses: ==@:8:P<E;GF@EKJN@CC9<8E8CPQ<;LJ@E>K?<DF;@=@<;
@EK<EK	KF	KI<8KD$//+FGLC8K@FE
/?<GI@D8IP<==@:8:P<E;GF@EK@JK?<:?8E><=IFD98J<C@E<8K2<<B@EK?<
;8@CP8M<I8><ELD9<IF=<G@JF;<JF=LI@E8IP@E:FEK@E<E:<8JI<:FI;<;@EK?<	;8P9C8;;<I;@8IP

FDG8I@JFEF=*/*308E;GC8:<9F8K2<<B=FIK?<GI@D8IP<==@:8:P<E;GF@EK8E;FK?<I:FEK@ELFLJ
<E;GF@EKJN@CC9<G<I=FID<;LJ@E>8E8CPJ@JF=:FM8I@8E:<N@K?KI<8KD<EK8J8=8:KFI8E;98J<C@E<M8CL<8E;K?<
ELD9<IF=LI><E:P@E:FEK@E<E:<<G@JF;<JI<GFIK<;8K98J<C@E<≤FI;8@CP<G@JF;<JFM<IK?<	;8P9C8;;<I
;@8IP8K98J<C@E<8J:FM8I@8K<J
/?<:FE=@;<E:<@EK<IM8C$=FIK?<C<8JKJHL8I<J'.D<8E;@==<I<E:<
9<KN<<E*/*308E;GC8:<9FN@CC9<:FEJKIL:K<;

FDG8I@JFEF=*/*308E;GC8:<9F8K2<<B=FIK?<GIFGFIK@FEF=G8K@<EKJN@K?I<;L:K@FE@E
LI@E8IP@E:FEK@E<E:<<G@JF;<J=IFD98J<C@E<8E;FK?<I:8K<>FI@:8C<E;GF@EKJN@CC9<8E8CPQ<;LJ@E>F:?I8E
(8EK<C	#8<EJQ<C(#D<K?F;N@K?K?<ELD9<IF=LI><E:P@E:FEK@E<E:<<G@JF;<JI<GFIK<;8K98J<C@E<≤FI
;8@CP<G@JF;<JFM<IK?<	;8P9C8;;<I;@8IP8K98J<C@E<8J8EFK?<I:8K<>FI@:8C=8:KFI
/?<$=FIK?<
F;;JI8K@FF=*/*30FM<IGC8:<9FN@CC9<:FEJKIL:K<;

.8=<KP<E;GF@EKJ@E:CL;@E>8;M<IJ<<M<EKJC89FI8KFIPLI@E<;8K8M@K8CJ@>EJ8E;+1-LI@E<MFCLD<N@CC9<
JLDD8I@Q<;;<J:I@GK@M<CP9PKI<8KD<EK98J<;FEK?<.8=<KP+FGLC8K@FE

Sample Size Calculation
/?<8JJLDGK@FEJLJ<;=FIJ8DGC<J@Q<:8C:LC8K@FE8I<=IFDK?<+?8J<$$$G@MFK8CJKL;@<J	8E;
	I<JLCKJ

JJLD@E>8D<8E8E;JK8E;8I;;<M@8K@FEF=:?8E><=IFD98J<C@E<8K2<<B@EK?<ELD9<IF=LI@E8IP
@E:FEK@E<E:<<G@JF;<J8I<	
X
8E;	
X
=FI*/*308E;GC8:<9FI<JG<:K@M<CPK?@JJKL;P
I<HL@I<JG8K@<EKJ*/*3G8K@<EKJ8E;GC8:<9FG8K@<EKJKFGIFM@;<GFN<I=FI;<K<:K@E>8
J@>E@=@:8EK;@==<I<E:<F=K?<GI@D8IP<==@:8:P<E;GF@EK:?8E><=IFD98J<C@E<@EELD9<IF=LI@E8IP@E:FEK@E<E:<
<G@JF;<J8K2<<B8K8J@>E@=@:8E:<C<M<C8CG?8F=LJ@E>8	J@;<;Q	K<JK8KK?<<E;	F=	JKL;P8E8CPJ@J

2@K?;IFGFLKI8K<K?<J8DGC<J@Q<I<HL@I<;=FIK?<G8K@<EKJKF9<I8E;FD@Q<;@EK?<JKL;PN@CC9<
8GGIFO@D8K<CPG8K@<EKJ



CC<I>8EConfidential 
+IFKF:FC(*	0.	0-*	
+IFKF:FCD<E;D<EK(8P
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CC<I>8EConfidential 
 
+IFKF:FC(*	0.	0-*	
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1. 
Background and Clinical Rationale  
Overactive Bladder and Urinary Incontinence 
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Epidemiology and Impact of Overactive Bladder 
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Currently Available Therapy 
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BOTOX Development Program 
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2. 
Study Objectives and Clinical Hypotheses  
2.1 
Study Objectives 
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2.2 
Clinical Hypotheses 
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3. 
Study Design 
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4. 
Study Population and Entry Criteria 
4.1 
Number of Subjects  
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4.2 
Study Population Characteristics 
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4.3 
Inclusion Criteria 
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Exclusion Criteria 
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4.5 
Permissible and Prohibited Medications/Treatments 
4.5.1 
Permissible Medications/Treatments 
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4.5.2 
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5. 
Study Treatments 
5.1 
Study Treatment and Formulation 
BOTOX 







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5.2 
Control Treatment 
BOTOX Placebo (Saline)  



5.3 
Methods for Masking/Blinding 
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5.4 
Treatment Allocation Ratio 
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Method for Assignment to Treatment Groups/Randomization 
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5.6 
Treatment Regimen and Dosing 
5.6.1 
Study Treatments 
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5.7 
Storage of Study Medications/Treatments 
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5.8 
Preparation/Dispensing of Study Medications 
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5.9 
Study Medication Administration 
5.9.1 
Day of Treatment 1 Criteria 
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5.9.2 
Prophylactic Antibiotics 
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5.9.3 
Use of Anesthesia 
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Treatment Procedure 
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5.10 
Retreatment 
5.10.1 
Request/Qualification for Treatment 2 
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5.10.2 
Day of Treatment 2 Criteria 
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6. 
Response Measures and Summary of Data Collection Methods 
6.1 
Efficacy Measures 
6.1.1 
Primary Measure 
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6.1.2 
Secondary Measures  
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6.2 
Safety Measures 
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6.3 
Examination Procedures, Tests, Equipment, and Techniques 
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6.3.1 
Medical History 
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6.3.2 
Physical Examination 
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6.3.3 
Vital Signs 
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6.3.4 
Bladder Diary 
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6.3.5 
Total Volume Voided 
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6.3.6 
Full Bladder Volume and Post-void Residual Urine Volume 
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6.3.6.1 
Post-void Residual Urine Volume < 200 mL  
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6.3.6.2 
Post-void Residual Urine Volume ≥ 200 mL and < 350 mL 
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6.3.6.3 
Post-void Residual Urine Volume ≥ 350 mL  
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6.3.7 
Clean Intermittent Catheterization 
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@E;N<CC@E>:8K?<K<I@JE<<;<;

6.3.7.1 
Initiation of Clean Intermittent Catheterization 
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6.3.7.2 
Cessation of Clean Intermittent Catheterization 
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6.3.8 
Adverse Events of Urinary Retention and Residual Urine 
Volume 
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6.3.9 
Dipstick Reagent Strip Test (Urine Dipstick) 
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6.3.10 
Urinalysis, Culture and Sensitivity 
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6.3.10.1 
Adverse Events of Urinary Tract Infection 
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6.3.11 
Pregnancy Test 
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
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6.3.12 
Screening Laboratory Tests 
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6.3.14 
Treatment Benefit Scale (TBS) 
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6.4 
Other Study Supplies 
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6.5 
Summary of Methods of Data Collection 
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7. 
Statistical Procedures 
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7.1 
Analysis Populations 
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7.2 
Collection and Derivation of Primary and Secondary Efficacy 
Assessments 
7.2.1 
Primary Efficacy Variables  
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7.2.2 
Secondary Efficacy Variables 
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7.3 
Hypothesis and Methods of Analysis 

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7.3.1 
Primary Efficacy Analyses 
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7.3.2 
Secondary Efficacy Analyses 
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7.3.4 
Safety Analyses 
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7.5 
Sample Size Calculation 
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7.6 
Primary Analysis   
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8. 
Study Visit Schedule and Procedures 
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8.1 
Subject Entry Procedures  
8.1.1 
Overview of Entry Procedures 
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8.1.2 
Informed Consent and Subject Privacy 
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8.2 
Washout Intervals 
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KFK?<JK8IKF=K?<J:I<<E@E>G<I@F;GIF:<;LI<J

8.3 
Procedures for Patient Rescreening 
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8.4 
Procedures for Final Study Entry 
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8.5 
Visits and Associated Procedures  
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D8B<K?<@IE<OKJ:?<;LC<;JKL;PM@J@K
8.6 
Unscheduled Visits 
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8.7 
Compliance with Protocol 
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K?<;<J@>E8K<;=@<C;@EK?<-!

8.8 
Early Discontinuation of Subjects 
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K?<G8IK@:@G8EK@JCFJKKF=FCCFN	LG

8.9 
Withdrawal Criteria 
+8K@<EKJ?8M<K?<I@>?KKFN@K?;I8N=IFDK?<JKL;P8K8EPK@D<8E;=FI8EPI<8JFEN@K?FLK
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8EPF=K?<=FCCFN@E>:I@K<I@88I<D<K
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:FDGIFD@J<JK?<G8K@<EKSJ89@C@KPKFG8IK@:@G8K<@EK?<JKL;P
 G8K@<EK@J;@8>EFJ<;N@K?E<NFII<:LII<EKD8C@>E8E:@<J<O:<GK98J8C:<CC:8I:@EFD8

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8.10 
Study Termination 
/?<JKL;PD8P9<JKFGG<;8K?@J?<IJKL;PJ@K<8K8EPK@D<9PK?<J@K<@EM<JK@>8KFI
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9. 
Adverse Events  
;M<IJ<<M<EKJF::LII@E>;LI@E>K?<JKL;PN@CC9<I<:FI;<;FE8E8;M<IJ<<M<EK:8J<I<GFIK
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9.1 
Definitions 
9.1.1 
Adverse Event 
EPLEKFN8I;D<;@:8CF::LII<E:<@E8G8K@<EKFI:C@E@:8C@EM<JK@>8K@FEJL9A<:K8;D@E@JK<I<;8
G?8ID8:<LK@:8CGIF;L:K8E;K?8K;F<JEFKE<:<JJ8I@CP?8M<8:8LJ8CI<C8K@FEJ?@GN@K?K?@J
KI<8KD<EK
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D<;@:@E8C@EM<JK@>8K@FE8CGIF;L:KN?<K?<IFIEFKI<C8K<;KFK?<D<;@:@E8C@EM<JK@>8K@FE8C
GIF;L:K
$E8;;@K@FE;LI@E>K?<J:I<<E@E>G<I@F;8;M<IJ<<M<EKJN@CC9<8JJ<JJ<;I<>8I;C<JJ
F=K?<8;D@E@JKI8K@FEF=8G?8ID8:<LK@:8CGIF;L:K

9.1.2 
Study-specific Definitions for Particular Adverse Events 
<=@E@K@FEF=;M<IJ< M<EKF=0I@E8IP-<K<EK@FE
E8;M<IJ<<M<EKF=LI@E8IPI<K<EK@FEJ?FLC;FECP9<I<:FI;<;N?<E8G8K@<EK?8J8I8@J<;
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8JJF:@8K<;JPDGKFDJ@<MF@;@E>;@==@:LCK@<JJ<EJ8K@FEF=9C8;;<I=LCCE<JJK?8K@EK?<
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K?<0/$N8JTJPDGKFD8K@:UFIT8JPDGKFD8K@:UFEK?<8;M<IJ<<M<EK<-!

9.1.3 
Serious Adverse Event 
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FLK:FD<J;<8K?8C@=<	K?I<8K<E@E>8;M<IJ<<M<EK@EG8K@<EK?FJG@K8C@Q8K@FEFIGIFCFE>8K@FE
F=<O@JK@E>?FJG@K8C@Q8K@FE8G<IJ@JK<EKFIJ@>E@=@:8EK;@J89@C@KP@E:8G8:@KPFI8:FE><E@K8C
8EFD8CP9@IK?;<=<:K
$DGFIK8EKD<;@:8C<M<EKJK?8KD8PEFKI<JLCK@E;<8K?9<C@=<	
K?I<8K<E@E>FII<HL@I<?FJG@K8C@Q8K@FED8P9<:FEJ@;<I<;8E. N?<E98J<;LGFE
8GGIFGI@8K<D<;@:8CAL;>D<EKK?<PD8PA<FG8I;@Q<K?<G8K@<EKFIJL9A<:K8E;D8PI<HL@I<
D<;@:8CFIJLI>@:8C@EK<IM<EK@FEKFGI<M<EKFE<F=K?<FLK:FD<JC@JK<;@EK?@J;<=@E@K@FE
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9.1.4 
Severity 
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9.1.5 
Relationship to Study Drug or Study Procedure 
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9<<E:8LJ<;9PK?<;IL>FIJKL;PGIF:<;LI<

9.2 
Procedures for Reporting Adverse Events 
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G8IK@:@G8EK@J:FEJ@;<I<;CFJKKF=FCCFN	LG

9.3 
Procedures for Reporting a Serious Adverse Event 
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G8><8E;I<:FI;<;FEK?<. !8O!FIDN@K?@E?FLIJF=8N8I<E<JJ
+8K@<EKJN@K?
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K?<FLK:FD<JI<GFIK<;KFCC<I>8E
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9.4 
Procedure for Reporting Pregnancy 
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8GGIFGI@8K<J8=<KP=FCCFN	LGN?@:?DLJK9<8D@E@DLDF=N<<BJJ@E:<C8JKJKL;P
KI<8KD<EK
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/?<@EM<JK@>8KFIFI
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9.5 
Procedures for Unmasking of Study Medication 
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8E;@EJK@KLK<8GGIFGI@8K<=FCCFN	LG:8I<
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/?<@EM<JK@>8KFI
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:8CC@E>@EKFK?<$2-.M@8G8JJNFI;	GIFK<:K<;8::<JJ
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10. 
Administrative Items 
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"L@;<C@E<FE"+

10.1 
Protection of Human Subjects 
10.1.1 
Compliance with Informed Consent Regulations (US 21 CFR 
Part 50) and Relevant Country Regulations 
2I@KK<E@E=FID<;:FEJ<EK@JKF9<F9K8@E<;=IFD<8:?JL9A<:KGI@FIKF8EPJKL;P	I<C8K<;
8:K@M@K@<JFIGIF:<;LI<J@EK?<JKL;P8E;FI=IFDK?<JL9A<:KJC<>8CCP8LK?FI@Q<;
I<GI<J<EK8K@M<
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CF:8CI<>LC8KFIPI<HL@I<D<EKJ

10.1.2 
Compliance with IRB or IEC Regulations 
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10.1.3 
Compliance with Good Clinical Practice 
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10.1.4 
Compliance with Electronic Records; Electronic Signatures 
Regulations (21CFR Part 11) 
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10.2 
Changes to the Protocol 
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10.3 
Patient Confidentiality 
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@E=FID8K@FE

10.3.1 
Patient Privacy 
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T#$+U

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10.4 
Documentation 
10.4.1 
Source Documents 
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10.4.2 
Electronic Case Report Form Completion 
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10.4.3 
Study Summary 
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10.4.4 
Retention of Documentation 
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10.5 
Labeling, Packaging, and Return or Disposal of Study 
Medications/Treatments 
10.5.1 
Labeling/Packaging 
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10.5.2 
Clinical Supply Inventory 
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10.5.3 
Return or Disposal of Study Medications/Treatments and/or 
Supplies 
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;@JGFJ<;F=G<ICF:8CJ@K<GI8:K@:<

10.6 
Monitoring by the Sponsor 
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10.7 
Handling of Biological Specimens 
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10.8 
Publications 
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LK?FIJ?@G8E;D8ELJ:I@GK
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J
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:FDGC<K@FEF=K?<=@E8CI<GFIKF=K?<DLCK@:<EK<IJKL;P<O:<GK8J8>I<<;N@K?CC<I>8E

10.9 
Coordinating Investigator 
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11. 
References 
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12.1 
Preparation of Study Medication 
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Confidential 
12.6 
Treatment Benefit Scale (TBS) 
before you received any study 
treatment in this trial

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12.7 
Package Insert 
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12.8 
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