A Phase II, Randomized Trial to Evaluate the Optimal Dosing of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products for Recurrent Clostridium Difficile Infection
Phase: PHASE2
Conditions: Recurrent Clostridium Difficile Infection
Sponsor: University of Pennsylvania



 
P M T f or Rec urre nt-C DI  
 
P a ge 2 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
T a ble of C o nte nts 
 
 
LI S T O F A B B R E VI A TI O N S .......................................................................................................................... 5 
S T U D Y S U M M A R Y  ...................................................................................................................................... 6 
B A C K G R O U N D A N D S T U D Y  R A TI O N A L E  ................................................................................................ 9 
1.  
I N T R O D U C TI O N .................................................................................................................................. 9 
1. 1.  B A C K G R O U N D A N D R E L E V A N T L I T E R A T U R E ......................................................................................... 9 
1. 2.  N A M E A N D D E S C RI P TI O N O F T H E IN V E S TI G A TI O N A L P R O D U C T  ............................................................ 1 0  
1. 2. 1.  
N o n -Cli ni c al D at a  .............................................................................................................. 1 1  
1. 2. 2.  
Cli ni c al D at a t o D at e  ......................................................................................................... 1 1  
1. 3.  D O S E R A TI O N A L E  ............................................................................................................................. 1 3  
2.  
S T U D Y O B J E C TI V E S  ....................................................................................................................... 1 3  
2. 1.  P RI M A R Y O B J E C TI V E  ........................................................................................................................ 1 3 
2. 2.  S E C O N D A R Y O B J E C TI V E  ................................................................................................................... 1 3  
2. 3.  E X P L O R A T O R Y O B J E C TI V E  ................................................................................................................ 1 3  
3.  
I N V E S TI G A TI O N A L P L A N ................................................................................................................ 1 3  
3. 1.  G E N E R A L D E SI G N ............................................................................................................................. 1 3  
3. 1. 1.  
S cr e e ni n g P h a s e  ............................................................................................................... 1 4  
3. 1. 2.  
St u d y I nt er v e nti o n P h a s e  .................................................................................................. 1 4  
3. 1. 3.  
P o st -P M T A d mi ni str ati o n m o nit ori n g: B e d si d e f or 6 0 Mi n ut e s  ......................................... 1 4  
3. 1. 4.  
P o st -P M T A d mi ni str ati o n F oll o w -U p  ................................................................................. 1 5  
3. 1. 5.  
All o c ati o n t o I nt er v e nti o n al Gr o u p  ..................................................................................... 1 6  
3. 2.  S T U D Y E N D P OI N T S  ........................................................................................................................... 1 6  
3. 2. 1.  
Pri m ar y St u d y E n d p oi nt s  .................................................................................................. 1 6  
3. 2. 2.  
S e c o n d ar y St u d y E n d p oi nt s  .............................................................................................. 1 6  
3. 2. 3.  
Pri m ar y S af et y E n d p oi nt s  ................................................................................................. 1 6  
4.  
S T U D Y P O P U L A TI O N A N D  D U R A TI O N O F P A R TI CI P A TI O N  ...................................................... 1 7  
4. 1.  IN C L U SI O N C RI T E RI A  ......................................................................................................................... 1 7  
4. 2.  E X C L U SI O N C RI T E RI A  ....................................................................................................................... 1 7  
4. 3.  S U B J E C T R E C R UI T M E N T  ................................................................................................................... 1 8  
4. 4.  D U R A TI O N O F S T U D Y P A R TI CI P A TI O N  ................................................................................................ 1 8  
4. 5.  T O T A L N U M B E R O F S U B J E C T S A N D S I T E S .......................................................................................... 1 8  
4. 6.  V U L N E R A B L E P O P U L A TI O N S  .............................................................................................................. 1 8  
5.  
S T U D Y I N T E R V E N TI O N  ................................................................................................................... 1 9  
5. 1.  D E S C RI P TI O N  ................................................................................................................................... 1 9  
5. 2.  IN T E R V E N TI O N R E GI M E N  ................................................................................................................... 1 9  
5. 3.  R E C EI P T  .......................................................................................................................................... 1 9  
5. 4.  S T O R A G E  ......................................................................................................................................... 1 9  
5. 5.  P R E P A R A TI O N A N D P A C K A GI N G  ......................................................................................................... 2 0  
5. 6.  B LI N DI N G  ......................................................................................................................................... 2 0  
5. 7.  A D MI NI S T R A TI O N A N D A C C O U N T A BI LI T Y  ............................................................................................. 2 0  
5. 8.  S U B J E C T C O M P L I A N C E M O NI T O RI N G  ................................................................................................. 2 1  
5. 9.  R E T U R N O R D E S T R U C TI O N O F IN V E S TI G A TI O N A L P R O D U C T  ................................................................ 2 1  
6.  
S T U D Y P R O C E D U R E S  ..................................................................................................................... 2 1  

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 1.  S C R E E NI N G A N D E N R O L L M E N T  .......................................................................................................... 2 1  
6. 1. 1.  
S ur v eill a n c e T e st R e v i e w .................................................................................................. 2 1  
6. 1. 2.  
M e di c al R e c or d R e vi e w f or I n cl u si o n/ E x cl u si o n Crit eri a  ................................................... 2 1  
6. 1. 3.  
I nf or m e d C o n s e nt .............................................................................................................. 2 1  
6. 1. 4.  
D e ci si o n o n M o d e of D eli v er y  ........................................................................................... 2 2  
6. 1. 5.  
R a n d o mi z ati o n  .................................................................................................................. 2 2  
6. 2.  S T U D Y IN T E R V E N TI O N P H A S E  ........................................................................................................... 2 2  
6. 2. 1.  
P M T Pr o d u ct R e c ei pt  ........................................................................................................ 2 2  
6. 2. 2.  
A d mi ni str ati o n  ................................................................................................................... 2 2  
6. 2. 3.  
P o st -I nt er v e nti o n 6 0 mi n ut e s ............................................................................................ 2 2  
6. 3.  S T U D Y F O L L O W -U P P H A S E  ............................................................................................................... 2 3  
6. 3. 1.  
F oll o w -u p 7 d a y s  ............................................................................................................... 2 3  
6. 3. 2.  
F oll o w -u p 3 0 d a y s  ............................................................................................................. 2 3  
6. 3. 3.  
F oll o w -u p 5 6 d a y s  ............................................................................................................. 2 3  
6. 3. 4.  
F oll o w -u p 9 0 d a y s  ............................................................................................................. 2 3  
6. 3. 5.  
E n d -of -st u d y vi sit at 1 8 0 d a y s  ........................................................................................... 2 4  
6. 4.  R E S C U E T H E R A P Y  ............................................................................................................................ 2 4  
6. 5.  U N S C H E D U L E D V I SI T S ...................................................................................................................... 2 4  
6. 6.  S U B J E C T W
I T H D R A W A L .................................................................................................................... 2 4  
6. 6. 1.  
D at a C oll e cti o n  .................................................................................................................. 2 5  
6. 6. 2.  
E arl y T er mi n ati o n Vi sit s  .................................................................................................... 2 5  
7.  
S T U D Y E V A L U A TI O N S A N D M E A S U R E M E N T S  ............................................................................ 2 7  
7. 1.  M E DI C A L R E C O R D R E VI E W  ............................................................................................................... 2 7  
7. 2.  P H Y SI C A L E X A MI N A TI O N  ................................................................................................................... 2 7  
7. 3.  V I T A L S I G N S ..................................................................................................................................... 2 7  
7. 4.  L A B O R A T O R Y E V A L U A TI O N S  .............................................................................................................. 2 7  
7. 5.  P R E G N A N C Y T E S TI N G  ....................................................................................................................... 2 7  
7. 6.  O T H E R E V A L U A TI O N S , M E A S U R E S  .................................................................................................... 2 7  
7. 7.  E F FI C A C Y E V A L U A TI O N S  ................................................................................................................... 2 7  
7. 8.  G E N E TI C T E S TI N G (O N L Y I F A P P LI C A B L E ) ........................................................................................... 2 8  
7. 9.  S A F E T Y E V A L U A TI O N S  ...................................................................................................................... 2 8  
7. 9. 1.  
D e vi ati o n s a n d E x c e pti o n s  ................................................................................................ 2 8  
7. 9. 2.  
S af et y P ar a m et er s ............................................................................................................ 2 8  
8.  
S T A TI S TI C A L P L A N  ......................................................................................................................... 2 9  
8. 1.  P RI M A R Y E N D P OI N T  ......................................................................................................................... 2 9  
8. 2.  S E C O N D A R Y E N D P OI N T S  .................................................................................................................. 2 9  
8. 3.  S A M P L E S I Z E A N D P O W E R D E T E R MI N A TI O N  ....................................................................................... 2 9  
8. 4.  S T A TI S TI C A L M E T H O D S  ..................................................................................................................... 3 0  
8. 4. 1.  
B a s eli n e D at a  .................................................................................................................... 3 0  
8. 4. 2.  
Effi c a c y A n al y si s  ............................................................................................................... 3 0  
8. 4. 3.  
I nt eri m A n al y si s ................................................................................................................. 3 0  
8. 4. 4.  
S af et y A n al y si s  .................................................................................................................. 3 0  
8. 4. 5.  
E x pl or at or y A n al y s e s  ........................................................................................................ 3 0  
8. 5.  S U B J E C T P O P U L A TI O N (S ) F O R A N A L Y SI S  ........................................................................................... 3 1  
9.  
S A F E T Y A N D A D V E R S E E V E N T S  ................................................................................................... 3 1  
9. 1.  D E FI NI TI O N S ..................................................................................................................................... 3 1  
9. 1. 1.  
A d v er s e E v e nt  ................................................................................................................... 3 1  
9. 1. 2.  
S eri o u s A d v er s e E v e nt  ..................................................................................................... 3 1  
9. 1. 3.  
A d v er s e E v e nt s of S p e ci al I nt er e st ( A E SI)  ....................................................................... 3 1  
9. 1. 4.  
E x p e ct e d A d v er s e E v e nt s  ................................................................................................. 3 2  

 
P M T f or Rec urre nt-C DI  
 
P a ge 4 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
9. 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 2  
9. 3.  R E P O R TI N G O F 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 3  
9. 3. 1.  
Pr e g n a n c y  ......................................................................................................................... 3 4  
9. 4.  T O XI CI T Y M A N A G E M E N T , S T O P PI N G R U L E S A N D S T U D Y T E R MI N A TI O N  ................................................ 3 4  
9. 5.  M E DI C A L M O NI T O RI N G  ...................................................................................................................... 3 5  
9. 5. 1.  
D at a a n d S af et y M o nit ori n g Pl a n  ...................................................................................... 3 5  
9. 5. 2.  
D at a S af et y M o nit ori n g B o ar d  ........................................................................................... 3 5  
1 0.  S T U D Y A D MI NI S T R A TI O N , 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  .................................... 3 5  
1 0. 1.  C O N FI D E N TI A LI T Y  ............................................................................................................................. 3 5  
1 0. 2.  F U T U R E U S E O F S T O R E D S P E CI M E N S A N D D A T A  ............................................................................... 3 5  
1 0. 3.  D A T A C O L L E C TI O N A N D M A N A G E M E N T  .............................................................................................. 3 5  
1 0. 4.  R E C O R D S R E T E N TI O N  ...................................................................................................................... 3 6  
1 1.  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  .................................................................. 3 6  
1 1. 1.  S T U D Y M O NI T O RI N G P L A N  ................................................................................................................ 3 6  
1 1. 2.  D A T A Q U A LI T Y A S S U R A N C E  .............................................................................................................. 3 6  
1 1. 3.  A U DI TI N G A N D IN S P E C TI N G  ............................................................................................................... 3 6  
1 2.  E T HI C A L C O N SI D E R A TI O N S  .......................................................................................................... 3 7  
1 2. 1.  R I S K S .............................................................................................................................................. 3 7  
1 2. 2.  B E N E FI T S  ......................................................................................................................................... 3 8  
1 2. 3.  R I S K B E N E FI T A S S E S S M E N T  ............................................................................................................. 3 8  
1 2. 4.  IN F O R M E D C O N S E N T P R O C E S S / HI P A A  A U T H O RI Z A TI O N  .................................................................. 3 8  
1 3.  S T U D Y FI N A N C E S  ............................................................................................................................ 3 8  
1 3. 1.  F U N DI N G S O U R C E  ............................................................................................................................ 3 8  
1 3. 2.  C O N F LI C T O F IN T E R E S T  .................................................................................................................... 3 8  
1 3. 3.  S U B J E C T S TI P E N D S O R P A Y M E N T S .................................................................................................... 3 9  
1 4.  P U B LI C A TI O N P L A N  ........................................................................................................................ 3 9  
1 5.  R E F E R E N C E S  ................................................................................................................................... 3 9  
 
T a ble of T a bles  
 
T a bl e 1: F M T d o si n g a n d a s s o ci at e d ri s k s.  ................................................................................................ 1 2  
T a bl e 2: S c h e d ul e of st u d y pr o c e d ur e s  ...................................................................................................... 2 6  
 
 
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 5 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
List of A b bre vi ati o ns  
 
A E:  A d verse e ve nt  
A E SI : A d verse e ve nt of s pecial i nterest 
A F T : acceler ate d f ail ure ti me  
A N C:  A bs ol ute ne utr o p hil c o u nt 
B MI:  b o d y m ass i n de x  
C DI:  Cl ostri di u m difficile  i nfecti o n 
C C H:  C hester C o u nt y H os pital 
C F R:  C o de of fe deral r e g ulati o ns 
C F U: c ol o n y- f or mi n g u nits 
C R C:  cli nical researc h c o or di nat or  
D S M B:  Data safet y m o nit ori n g b oar d 
EI A:  e nz y me i m m u n oassa y 
F M T:  Fecal Micr o bi ota Tra ns pla ntati o n  
g : gra ms  
HI P A A:  Healt h I ns ura nce P orta bilit y a n d A cc o u nta bilit y Act of 1 9 9 6  
H U P:  H os pital of t he U ni versit y of Pe n ns yl va ni a  
I C H: I nter nati o nal C o nf ere nce o n Har m o nisati o n 
I D S A: I nfecti o us Diseas es S ociet y of A merica 
I T T: i nte nti o n t o treat 
L G H:  La ncaster G e neral H os pital  
m- I T T: m o difie d i nte nti o n t o treat 
m L : milliliters  
N A A T:  n ucleic aci d a m plificati o n testi n g  
P A H:  Pe n ns yl v a nia H os pital  
P HI:  pr ot ecte d h ealt h i nf or mati o n 
P M P M C:  Pe n n Medici ne Pri ncet o n Me dical Ce nter  
P M T:  Pe n n Micr o bi o me T hera p y 
P PI:  pr ot o n p u m p i n hi bit or 
P P M C:  Pe n n -Pr es b yt eri a n Me dical Ce nter  
R- C DI:  Rec urr e nt Cl ostri di u m difficile  i nfecti o n 
S A E : Seri o us A d verse E ve nt 
SI R S:  s yste mic i nfla m m at or y res p o nse s y n dr o me  
S/ S C/ F -C DI:  se v ere or s e vere-c o m plicate d/f ul mi na nt Cl ostri di u m difficile  i nfecti o n 
S U S A R:  S us pecte d u ne x pecte d seri o us a d vers e reacti o n  
W B C:  w hite bl o o d cells 
 

 
P M T f or Rec urre nt -C DI  
 
P a ge 6 of 4 1  
 
 
P M T f or Rec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
St u d y  S u m m ar y  
Title  
A P hase II, Ra n d o mize d Trial  t o E val uate t he O pti mal D osi n g of Fecal 
Micr o bi ota Tra ns pla ntati o n usi n g t he Pe n n Micr o bi o me T hera p y Pr o d ucts 
f or Rec urre nt Cl ostri di u m difficile  I nfecti o n 
 
S h ort Title  
P M T f or R ec urr e nt -C DI  
I R B N u m ber 
8 3 2 9 6 3  
P h ase  
P hase II  
Met h o d ol o g y  
Ra n d o mize d, o pe n la bel, c o m parati ve  
St u d y D ur ati o n  
T w o years  
St u d y Ce nter  
Pe n n Me dici ne -- U ni versit y of Pe n ns yl va nia H ealt h S yste m 
O bjecti ves  
•  Pri m ar y : T o e v al uate t h e effi cac y of fecal micr o bi ota 
tra ns pla ntati o n ( F M T) perf or me d usi n g t he Pe n n Micr o bi o me 
T hera p y ( P M T) s uite of pr o d ucts t o treat s u bjects wit h rec urre nt 
Cl ostri di u m difficile  i nfecti o n ( R-C DI)  b y c o m pari n g t he cli nical 
o utc o mes of t w o treat me nt strate gi es: ( 1) si n gle-d ose P M T; ( 2) 
t w o d oses of P M T a d mi nistere d wit hi n 2 4 h o urs. 
•  Sec o n d ar y : T o deter mi ne w het her m ass of fecal 
material or q ua ntitati ve c ult ure better pre dicts efficac y 
of P M T pr o d ucts use d t o treat s u bjects wit h R- C DI.  
•  E x pl or a t or y: T o c haract erize differe nces i n t he efficac y 
of fecal micr o bi ota tra ns pla ntati o n f or R- C DI bas e d o n 
r o ute of a d mi nistrati o n, u ni q ue bacteri al c o m m u nit y 
feat ur es of t he a d mi nistere d P M T d ose, a n d h ost 
i m m u ne res p o nse t o i nfecti o n. 
N u m ber of 
S u bjects  
Tar get e nr oll me nt: 3 0 0 s u bjects . 

 
P M T f or Rec urre nt-C DI  
 
P a ge 7 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
M ai n I ncl usi o n 
a n d E xcl usi o n 
Criteri a  
I n cl usi o n Criteria: 
1.  Sec o n d  or greater e pis o de of C DI (first or greater rec urre nce)  
wit hi n 1 2 m o nt hs, wit h s y m pt o ms i ncl u di n g b o w el m o ve me nts 
altere d i n fre q ue n c y or c o nsiste nc y fr o m baseli ne. 
2.  St o ol p ositi ve f or C. difficile  t o xi n b y EI A or t o xi n ge n e b y 
N A A T wit hi n 6 0 da ys of e nr oll me nt. 
3.  At least o ne a d diti o nal pri or p ositi ve st o ol test f or C. difficile  
wit hi n t he pri or 1 2 m o nt hs ( EI A or N A A T as a b o ve). 
4.  A ge ≥ 1 8 years.  
5.  Mi ni m u m of 7 2 h o urs of recei pt of sta n d ar d- of -care ( va nc o m yci n 
or fi da x o mici n) a nti bi otic treat me nt f or R - C DI pri or t o 
i nter ve nti o n. 
 
E x cl usi o n Criteria:  
1.  E vi de nce of c ol o n/s mall b o wel perf orati o n at t he ti me of st u d y 
scree ni n g 
2.  G oals of care are directe d t o c o mf ort rat her t ha n c urati ve 
meas ures.  
3.  M o derate ( A N C < 1 0 0 0 cells/ u L) or se vere ( A N C < 5 0 0 cells/ u L) 
ne utr o pe nia.  
4.  K n o w n f o o d aller g y t h at c o ul d lea d t o a na p h yl a xis. 
5.  Pre g n a nc y  
6.  Meeti n g criteria f or S/ S C/ F - C DI wit hi n 2 4 h o urs of pla n ne d trial 
e nr oll me nt, w hic h we d efi ne as a n y o ne of t he f oll o wi n g: ( 1) 
le u k oc yt osis wit h peri p h eral W B C ≥ 1 5, 0 0 0 cells/ m L; ( 2) 
h y p ote nsi o n wit h s yst olic bl o o d press ure s ustai ne d < 9 0 m m H g f or 
t hree or more h o urs or re q uiri n g press ors; ( 3) pr o vi der 
d oc u me ntati o n of ile us or ra di ol o gic e vi de n ce of b o wel dilati o n or 
me gac ol o n; ( 4) ac ute ki d ne y i nj ur y wit h i ncreas e i n baseli ne 
ser u m creati ni ne le vel b y ≥5 0 % or ne w dial ysis i nitiati o n; ( 5) 
ser u m lactate > 2. 2 m m ol/ L; or ( 6) ≥ 3 s yste mic i nfla m mat or y 
res p o nse s y n dr o me ( SI R S) criteria ( w hic h i ncl u de heart rate > 9 0 
beats per mi n ute, res pirat or y rate > 2 0 breat hs per mi n ute or 
Pa C O 2 < 3 2 m m H g, te m perat ure > 3 8º C or < 3 6º C, W B C > 1 2, 0 0 0 
cells/ u L, < 4,0 0 0 cells/ u L, or > 1 0 % i m mat ure ( ba n d) f or ms ). 
7.  Recei pt of F M T or e nr oll me nt i n a cli nical trial f or F M T wit hi n t he 
last 3 m o nt hs .  

 
P M T f or Rec urre nt-C DI  
 
P a ge 8 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
I n vesti g ati o n al 
Pr o d uct  
 
1.  Pe n n Micr o bi o me T hera p y –  0 0 1 ( P M T -0 0 1): n o m ore t ha n 
1 5 2 m L  s us pe nsi o n f or rectal e ne ma fr o m 4 0 g h u ma n st o ol, 
c o m prisi n g a t otal of 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial 
C F Us/ d ose. 
2.  Pe n n Micr o bi o me T hera p y – 0 0 2 ( P M T- 0 0 2): n o m ore t ha n 1 5 2 
m L  s us pe nsi o n f or i ntra gastric, i ntra d u o de n al, or i ntrajej u nal 
a d mi nistrati o n fr o m 4 0 g h u ma n st o ol, c o m prisi n g 1 x 1 0 8 – 1 x 1 01 2 
a naer o bi c bact erial C F Us/ d ose. 
3.  Pe n n Micr o bi o me T hera p y – 0 0 3 ( P M T- 0 0 3): n o m ore t ha n 3 2 
ca ps ules f or oral a d mi nistrati o n fr o m 4 0 g d o n ate d st o ol, 
c o m prisi n g 1 x 1 0 8– 1 x 1 0 1 2 a naer o bic bacterial C F Us/ d ose. 
 
P M T - 0 0 1, P M T- 0 0 2, P M T- 0 0 3, are p ac k a ge d f or si n gle- d os e 
a d mi nistrati o n . 
 
D ur ati o n of 
a d mi nistr ati o n  
1 0 – 9 0 mi n utes (tar get 3 0 mi n utes)  
Ref ere nce 
t her a p y 
Si n gle d ose of Pe n n Micr o bi o me T hera p y pr o d u ct. 
St atistic al 
Met h o d ol o g y 
Pri mar y o utc o m e will be res ol uti o n of diarr hea wit h o ut rec urre nce 
assesse d at  8 w ee ks ( 5 6 d a ys) after i nter ve nti o n. L o gistic re gressi o n 
a nal ysis will be use d t o assess if re peat d osi n g is s u peri or t o si n gle d os e . 
S af et y 
E v al u ati o ns  
We will m o nit or safet y of a d mi nistrati o n as well as safet y of t he 
i n vesti gati o nal pr o d u cts, i n ter ms of a d vers e e ve nts as liste d i n Secti o n  9 .  
D at a a n d S af et y 
M o nit ori n g Pl a n  See Secti o n 1 0 .  
 
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 9 of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
B ac k gr o u n d a n d St u d y R ati o n ale  
T his st u d y will be c o n d u cte d i n f ull acc or da nce all a p plica ble U ni versit y of Pe n ns yl va nia 
Researc h P olicies a n d Pr oce d ures a n d all a p plica ble Fe d eral a n d st ate la ws a n d  re g ulati o ns 
i ncl u di n g 4 5 C F R 4 6 , 2 1 C F R Parts 5 0 , 5 4 , 5 6 , 3 1 2  a n d G o o d Cli nical Practice : C o ns oli date d 
G ui deli nes a p pr o ve d b y t he I nter n ati o nal C o nfere nce o n Har m o nisati o n (I C H). All e pis o des of 
n o nc o m plia nce will be d oc u me nte d. 
1.  I ntr o d ucti o n 
Fecal micr o bi ota tra ns pla ntati o n ( F M T) is rec o m me n de d treat me nt f or rec urre nt Cl ostri di u m 
difficile  i nfecti on ( R -C DI) base d o n its s uccess i n m ulti ple trials tar geti n g s u bjects wit h mil d or 
m o derate C DI s y m pt o ms ( Mc D o nal d 2 0 1 8; Kell y BJ 2 0 1 8). F M T pr o d uct d osi n g has t y picall y 
bee n defi n e d b y t he mass of h u ma n st o ol use d t o ge nerat e t he d ose. H o we v er, t he F M T pr o d ucts 
use d t o treat R - C DI are n ot sta n dar dize d, a n d trials t o date ha ve de m o nstrate d a lar ge ra n ge of 
efficac y ( Ca m mar ota 2 0 1 4; va n N o o d 2 0 1 3; Y o u n gster 2 0 1 6; K ell y C R 2 0 1 6). A rece nt trial 
utilizi n g a greater mass of starti n g st o ol materi al de m o nstrate d g reater efficac y t ha n pri or tri als 
( Ka o 2 0 1 7), raisi n g t h e q uesti o n of h o w t he mass of st o ol material use d t o ge n erat e F M T pr o d uct 
c o ntri b utes t o t he effi cac y of t he pr o d uct. A n ot her p ossi ble e x pla nati o n f or t he var yi n g efficac y 
of F M T pr o d u cts is t he f act t hat t he y ori gi nate fr o m differe nt st o ol d o n ors, eac h wit h a u ni q u e 
g ut micr o bi o me a n d c o nce ntrati o n of micr o bes ( See katz 2 0 1 4). We will perf or m a ra n d o mize d 
c o ntr olle d trial t o e val uat e t he saf et y a n d efficac y of Pe n n Micr o bi o me T hera p y ( P M T) pr o d u cts 
f or F M T i n s u bjects wit h R - C DI. T h e P M T pr o d u cts c o m prise t hree differe nt f or m ulati o ns of 
F M T f or oral, e nteric ( vi a t u be), or r ectal d eli ver y. T he trial will c o m pare t he effi cac y of 
sta n dar d- d ose F M T ( a si n gle d ose deri ve d fr o m 4 0 g starti n g st o ol mass a d mi nistere d o nce) 
vers us d o u ble- d ose F M T (i.e., t w o si n gle d os es, or t he e q ui vale nt of 8 0 g st arti n g st o ol mass, 
a d mi nistere d wit hi n 2 4 h o urs) i n t he treat me nt of R- C DI. We will f urt her e val uate t he 
c o nce ntr ati o n of a naer o bi c bacteria, w hic h i ncl u d e t he ta x a m ost fre q ue ntl y i de ntifie d as 
pr otecti ve a gai nst C DI ( Lee YJ 2 0 1 7), i n F M T pr o d ucts t o deter mi ne w het her a d mi nistere d st o ol 
mass or bacterial c o nce ntrati o n better pre dict F M T efficac y. We will als o e x pl ore micr o bi o me 
differe n ces b et wee n F M T d o n ors a n d differe n ces i n h ost i m m u ne res p o nse t o C DI pre dict ors of 
F M T efficac y. T her e is n o place b o ar m i n t he trial beca use F M T is alrea d y esta blis he d as 
rec o m me n de d t h era p y f or R-C DI . 
1. 1.  
B ac k gr o u n d a n d Relev a nt Liter at ure  
As rece ntl y as 2 0 1 5, t he Ce nters f or Dis ease  C o ntr ol a n d Pre ve nti o n ( C D C) i de ntifie d Cl ostri di u m 
difficile  i nfecti o n ( C DI) as a n “ ur ge nt” t hreat ass ociate d wit h u p war ds of 5 0 0, 0 0 0 i nfecti o ns i n t he 
U nite d States eac h year a n d res ulti n g i n o ver 1 5, 0 0 0 deat hs. C DI is c haracterize d b y a cli nical 
s y n dr o me t hat t y picall y i ncl u des l o ose, fre q u e nt b o wel m o ve me nts a n d a b d o mi nal pai n, w hic h 
occ ur as a r es ult of t o xi n pr o d ucti o n b y c ol o nic C. difficile . C DI occ urs i n p atie nts c ol o nize d wit h 
t o xi ge nic C. difficile  a n d i n patie nts w h o ha ve n e wl y ac q uire d C. difficile . Esti mates of t he relati ve 
c o ntri b uti o ns of persiste nt c ol o nizati o n a n d ne w ac q uisiti o n t o i nci de nt C DI var y. I n b ot h cases, 
t he pat h o ge nesis of C DI i n v ol ves de pleti o n of n o n-C. difficile  c ol o nic micr o bi ota, altere d bile aci d 
meta b olis m, ger mi nati o n of (r esi de nt or rece ntl y i n geste d) C. difficile  s p ores, e x pa nsi o n of a 
p o p ulati o n of ve getati ve C. difficile , t o xi n pr o d ucti o n, a n d c ol o nic i nfla m mati o n. Ke y c halle n ges 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 0  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
ass ociate d wit h C DI i ncl u de its rec urre n ce aft er a p pr o priate a nti bi otic treat me nt ( R -C DI), a n d its 
pr o gressi o n t o a m or e se v ere disease state wit h s yst e mic si g ns of i nfla m mati o n or e ve n s e psis. T he 
latter, ter me d se ver e or se vere-c o m plicate d/f ul mi na nt C DI ( S/ S C/ F -C DI), ofte n re q uires e xte n de d 
h os pitalizati o ns, ma y re q uire c olect o m y, a n d is ass oc iate d wit h hi g h rates of m ortalit y ( Kell y BJ 
2 0 1 8). At prese nt, a nti bi otic treat me nt is t he rec o m me n de d t hera p y f or earl y R -C DI, a n d a nti bi otic 
treat me nt f oll o w e d b y F M T is t he rec o m me n d e d t hera p y f or later R-C DI. A nti bi otics are t h e 
rec o m me n de d t h era p y f or S/ S C/ F- C DI ( M c D o nal d 2 0 1 8).  
1. 2.  
N a m e a n d Descri pti o n of t he I nvesti g ati o n al Pr o d uct 
 
Pe n n Micr o bi o me T her a p y s uite of i n vesti gati o nal pr o d ucts  
 
•  Pe n n Micr o bi o me T her a p y – 0 0 1, hereafter referre d t o as P M T- 0 0 1 
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol i nt o n o m ore t ha n 1 5 2 m L s us pe nsi o n of 
i n vesti gati o nal pr o d u ct. 
o  E ne ma a d mi nistere d rect all y  
 
•  Pe n n Micr o bi o me T her a p y – 0 0 2, hereafter referre d t o as P M T - 0 0 2,   
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol i nt o n o m ore t ha n 1 5 2 m L s us pe nsi o n of 
i n vesti gati o nal pr o d u ct. 
o  S us pe nsi o n a d mi nistere d i ntra gastric, i ntra d u o d e nal, or i ntrajej u nal 
 
•  Pe n n Micr o bi o me T her a p y – 0 0 3, hereafte r referre d t o as P M T - 0 0 3,   
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol a n d c o nce ntrate d t o fill n o m ore t ha n 3 2 
ca ps ules  
o  All 3 2 c a ps ules t o be a d mi nistere d orall y  
 
C he mical Na me a n d Str u ct ure:  
P M T - 0 0 1: Fecal Micr o bi ota f or Tra ns pla nt, e ne m a pr o d uct  
P M T - 0 0 2: Fecal Micr o bi ota f or Tra ns pla nt, s us pe nsi o n pr o d uct  
P M T - 0 0 3: Fecal Micr o bi ota f or Tra ns pla nt, ca ps ul e pr o d uct  
 
T he t hree i n v esti gati o nal pr o d ucts, P M T- 0 0 1, 0 0 2, 0 0 3, are c o m p os e d of d o nate d st o ol fr o m 
healt h y d o n ors t hat meet t he d o nati o n criteria.  T h e st o ol sa m ple is c o m p ose d of a p pr o xi matel y 
7 5 % water a n d 2 5 % or ga nic a n d i n or ga nic s oli ds.  T y picall y, 1 g of st o ol c o ntai ns a p pr o xi matel y 
1 0 9 bacterial cells.  T he st o ol sa m ple is s u bse q ue ntl y  pr ocesse d wit h p h os p hate-b uffere d sali ne 
( P B S) c o ntai ni n g 1 0 % gl ycer ol a n d f or m ulate d as a s us pe nsi o n f or P M T- 0 0 1 a n d P M T- 0 0 2 or 
c o nce ntr ate d a n d e nca ps ulate d  f or P M T- 0 0 3. 
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 1  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1. 2. 1.  N o n -Cli nic al D at a  
F M T as a tr eat me nt m o d alit y f or C DI di d n ot ta ke t he c o n ve nti o nal pat h of dr u g d e vel o p me nt. 
Fecal tra ns pla nts see m t o date as f ar bac k as 4t h ce nt ur y C hi na, a n d ha v e rece ntl y bec o me 
rec o m me n de d t h era p y f or R- C DI o n t he basis of s e veral ra n d o mize d trials ( Mc D o nal d 2 0 1 8; va n 
N o o d 2 0 1 3; Y o u n gster 2 0 1 6; Kell y C R 2 0 1 6; Ka o 2 0 1 7), e ve n as t here re mai ns si g nifica nt 
heter o ge n eit y a m o n g F M T pr o d ucts. T here is n o esta blis he d sta n dar d f or n o n- cli nical testi n g of 
F M T pr o d ucts gi ve n u n certai nt y as t o w hat micr o bial feat ures deter mi ne p ote nc y ( B oja n o va 
2 0 1 6). T he treat me nt pr ot oc ol o utli ne d here is bas e d o n t he res ults p u blis he d fr o m pri or st u dies 
t hat ha ve dri ve n t he st a n dar ds a d o pte d i n o ur R- C DI a n d S/ S C/ F- C DI pr ot oc ols ( Ha milt o n 2 0 1 2; 
Kell y BJ 2 0 1 8; Ca m mar ota 2 0 1 7 ; Krajice k 2 0 1 8).  
1. 2. 2.  Cli nic al D at a  t o D ate  
T here is n o a v aila ble cli nical researc h d ata t o date o n t he i n vesti gati o nal pr o d ucts P M T - 0 0 1, 0 0 2 
or 0 0 3. F M T has b ee n est a blis he d as effecti ve a n d is rec o m me n de d f or treat me nt of m ulti pl y 
rec urre nt C DI o n t he b asis of se ver al ra n d o mize d c o ntr olle d trials ( Mc D o nal d 2 0 1 8; va n N o o d 
2 0 1 3; Y o u n gster J A M A 2 0 1 4; Kell y C R 2 0 1 6; Ka o 2 0 1 7). See T a ble 1  f or a s u m mar y of t he 
ris ks descri be d i n t he literat ure. 

 
P M T f or Rec urre nt -C DI  
 
P a ge 1 3  of 4 1  
 
 
P M T f or Rec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
 
1. 3.  
D ose R ati o n ale 
T here are n o pre -cli nical or cli nical data f or t he P M T s uite of F M T pr o d u cts t o i nf or m o pti mal 
d ose. H o we v er, t her e ar e e xte nsi ve o bser vati o nal st u dies a n d se veral ra n d o mize d trials t hat 
s u g gest a n F M T d ose d eri ve d fr o m 3 0- 1 0 0 g of h u ma n st o ol is effecti ve t o treat R-C DI 
( Ca m mar ota 2 0 1 4; va n N o o d 2 0 1 3; Y o u n gster J A M A 2 0 1 4; Kell y C R 2 0 1 6). A rece nt trial 
utilizi n g a greater mass ( 8 0 -1 0 0 g) of starti n g st o ol material de m o nstrate d g reater efficac y t ha n 
pri or trials ( Ka o 2 0 1 7), r aisi n g t he q uesti o n of h o w t he mass of st o ol material use d t o ge nerate 
F M T pr o d uct c o ntri b utes t o t he efficac y of t he pr o d uct. We will e val uate t he safet y a n d efficac y 
of P M T pr o d ucts f or F M T t o treat R- C DI, c o m pari n g si n gle - d ose ( 4 0 g starti n g st o ol mass) 
vers us d o u ble- d ose (i.e., t w o P M T d oses a d mi nistere d wit hi n 2 4 h o urs). T h e P M T pr o d ucts 
pr o d uce d fr o m t hese 4 0 g st o ol mass c o ntai n a ra n ge of 1e 8 – 1e 1 2 a naer o bi c bacterial C F Us, s o 
t he d o u ble- d ose i nter v e nti o n will c o ntai n t wice t hat. T h o u g h t he differe nce i n a naer o bi c C F Us is 
mar gi n al bet wee n si n gl e a n d d o u ble- d ose i nter v e nti o ns, ot her bacterial ta x a ma y scale m ore 
directl y wit h st o ol mass, a n d rece nt trial data ( Ka o 2 0 1 7) s u g gest t hat s uc h a differe nce mi g ht be 
cli nicall y mea ni n gf ul.  
2.  St u d y  O bjecti ves  
2. 1. 
Pri m ary O bjective  
T o e val uate t he effi cac y of fecal micr o bi ota tra ns pla ntati o n ( F M T) p erf or me d usi n g t he Pe n n 
Micr o bi o me T her a p y ( P M T) s uite of pr o d ucts t o treat s u bjects wit h rec urre nt Cl ostri di u m 
difficile  i nfecti o n ( R -C DI) b y c o m pari n g t he cli nical o utc o mes of t w o treat me nt strate gies: ( 1) 
si n gle- d os e P M T; ( 2) t w o d oses of P M T a d mi nistere d wit hi n 2 4 h o urs. 
2. 2. 
Sec o n d ary O bjective  
T o deter mi ne w h et her m ass of fecal materi al or q ua ntitati ve c ult ure better pre dicts  efficac y of 
P M T pr o d ucts use d t o treat s u bjects wit h R- C DI . 
2. 3.  
E x pl or at ory O bjective  
T o c har acterize diff ere n ces i n efficac y of fecal micr o bi ota tra ns pla ntati o n f or R - C DI base d o n 
( 1) r o ute of a d mi nistrati o n, ( 2) u ni q ue bacterial c o m m u nit y feat ures of t he a d mi nistere d P M T 
d ose, a n d ( 3) feat ures of h ost i m m u ne res p o nse t o C DI. 
3.  I n vesti g ati o n al Pl a n 
3. 1. 
Ge ner al Desi g n  
We will perf or m a r a n d o mize d, c o ntr olle d, o pe n la bel trial. S u bjects will be scree ne d t o e v al uate 
if t he y meet i ncl usi o n criteria f or rec urre nt C DI. If eli gi ble, s u bjects will partici pate i n t he 
i nf or me d c o nse nt pr o cess. F oll o wi n g i nf or me d c o nse nt s u bject prefere n ce a n d g ui da n ce of t he 
referri n g/ pri mar y car e tea m will be use d t o i de ntif y r o ute of a d mi nistrati o n. Stratifie d 
ra n d o mizati o n will t he n be use d b y r o ute of a d mi nistrati o n t o ra n d o mize s u bjects t o o ne of t w o 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 4  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
ar ms: ( 1) si n gle d ose of P M T, or ( 2) t w o d oses of P M T a d mi nistere d wit hi n 2 4 h o urs. We will 
c o m pare t he t w o treat me nt strate gi es’ s uccess  i n ac hie vi n g cli nical res ol uti o n of diarr hea i n 
s u bjects wit h R- C DI. S u bjects ra n d o mize d t o recei ve t w o d oses of F M T will recei ve t w o d os es 
fr o m t he sa me d o n or ( b ut n ot necessaril y fr o m t he sa me ma n ufact uri n g batc h). T he r o ute of 
a d mi nistrati o n ma y be dif fer e nt f or t he s ec o n d d os e per s u bject’s treati n g p h ysicia n a n d s u bject 
prefere nce. S u bjects will be f oll o we d u ntil 1 8 0 da ys after t heir l ast P M T d ose. 
3. 1. 1.  Scree ni n g P h ase  
Beca use F M T is rec o m me n de d t her a p y f or R -C DI, p ote ntial s u bjects will be i de ntifie d t hr o u g h 
acti ve scr ee ni n g a n d b y r eferral fr o m a care pr o vi der wit hi n t he U ni versit y of Pe n ns yl va ni a 
Healt h S yste m ( Pe n n M e dici ne). P ote ntial s u bjects’ healt h rec or ds will be i nitiall y s cree ne d b y a 
st u d y tea m me m ber t o e v al uate if t he i ncl usi o n/e x cl usi o n criteria ma y b e met. If a p ote ntial 
s u bject ma y m eet i ncl usi o n/e x cl usi o n criteria, t he p ote ntial s u bject ( or t heir desi g nat e d me dical 
decisi o n - ma ker) will be c o ntacte d i n pers o n or b y tele p h o ne t o disc uss partici pati o n. If a 
p ote ntial s u bject is c urre ntl y a d mitte d t o t he h os pital a n d if t he pri mar y tea m is n ot alrea d y  a w are 
of p ote ntial eli gi bilit y, t h e st u d y tea m will c o ntact t he s u bject’s i n patie nt care tea m t o as certai n 
w het her t he car e tea m has a n y o bj ecti o n t o t he st u d y tea m e nr olli n g t h e p ote ntial s u bject. The 
p ote ntial s u bject ( or t heir desi g nat e d me dical d ecisi o n -ma ker) will be c o ntacte d t o disc uss 
partici pati o n, fi nal scr ee ni n g f or i n cl usi o n/e x cl usi o n criteria will be p erf or m e d, a n d i nf or me d 
c o nse nt will be o btai ne d. 
3. 1. 2.  St u d y I nter ve nti o n P h ase  
R- C DI tri al i nter ve nti o ns ma y  b e perf or me d i n pati e nt or o ut patie nt at t he liste d st u d y sites i n 
secti o n 4. 5 . O nce s u bjects are e nr olle d a n d i nf or m e d c o nse nt is o btai ne d, s u bjects will be 
assesse d f or t h eir a bilit y t o t olerate or al ca ps ules, gastric/ d u o de nal /jej u nal i nf usi o n, a n d e ne ma 
( per acti ve pres cri be d me dicati o n list a n d/ or o pi ni o n of referri n g care pr o vi der); t he s u bject’s 
prefere nce a n d t he g ui d a nce of t he ref erri n g care pr o vi der will deter mi ne if P M T - 0 0 1, P M T- 0 0 2, 
or P M T - 0 0 3 will be use d. F oll o wi n g t his, stratifie d ra n d o mizati o n t o si n gle - or d o u ble- d ose 
strate g y will be perf or me d wit hi n r o ute of deli ver y gr o u ps (i.e., wit hi n P M T- 0 0 1, P M T- 0 0 2, or 
P M T - 0 0 3 gr o u ps). A d mi nistrati o n of a si n gle d os e of t he pr o d u ct will ta ke place o ver 1 0 t o 9 0 
mi n utes (tar get 3 0 mi n utes). A sec o n d d ose will be gi v e n bet wee n 4 a n d 2 4 h o urs after t h e first 
d ose. T he r o ute of a d mi nistrati o n ma y be differe nt f or t he sec o n d d ose per s u bject’s treati n g 
p h ysicia n a n d s u bject pr efere n ce. If a s u bject is u na ble t o ta ke at least 5 0 % of a d ose, t he y will 
be per mitte d t o o pt t o  recei ve a diff ere nt r o ute of a d mi nistrati o n f or o ne d ose wit hi n 2 4 h o urs. 
A n y a nti bi otics pre vi o usl y pr escri be d f or t he treat me nt of C DI will be st o p pe d 1 2- 4 8 h o urs 
(tar get 2 4 h o urs) pri or t o t he i nter ve nti o n. 
3. 1. 3.  P ost -P M T A d mi nistr ati o n m o nit ori n g: Be dsi de f or 6 0 Mi n utes  
S u bjects will be m o nit ore d a t 3 0 a n d 6 0 mi n utes f oll o wi n g c o m pleti o n of P M T a d mi nistrati o n. 
S u bjects will be vis uall y o bser ve d f or si g ns of as pirati o n or ot her res pirat or y distress ( P M T- 0 0 2 
a n d P M T- 0 0 3), a b d o mi n al pai n, v o miti n g, ot her si g ns of aller gic reacti o n, a n d c ha n ges i n vital 
si g ns ( P M T- 0 0 1, P M T- 0 0 2, a n d P M T- 0 0 3). Vital si g ns (te m perat ure, h eart rate, res pirat or y rate, 
bl o o d press ure, a n d o x y g e n sat urati o n) will be c h ec ke d . T he f oll o wi n g vital si g n c ha n ges will be 
rec or d e d if o bser v e d, a n d will pr o m pt n otificati o n of t he pri mar y cli nical care tea m:  ( 1) h eart rate 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 5  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
increas e or decrease b y greater t ha n or e q u al t o 3 0 beats per mi n ute ; ( 2) res pirat or y rate i n crease 
or decr ease b y greater t h a n or e q ual t o 1 0 breat hs per mi n ute or if res pirat or y rate dr o ps b el o w 1 0 
or i ncreases a b o v e 2 5 (if res pirat or y r ate n ot alrea d y o utsi de t hese ra n ges) ; ( 3) te m perat ure: 
i ncreas e or decrease b y greater t ha n or e q u al t o 2 de grees Fa hre n heit, or if te m perat ure dr o ps 
bel o w 9 6° F or i n creases a b o ve 1 0 0. 4° F (if te m perat ure n ot alrea d y o utsi de t hese ra n ges); ( 4) 
o x y ge n s at urati o n decrease b y great er t ha n or e q u al t o 5 % (s ustai ne d f or m ore t ha n 2 0 sec o n ds) 
or if o x y ge n sat ur ati o n dr o ps bel o w 9 0 % ( o n c urre nt a m o u nt of o x y ge n d eli vere d, s ustai ne d f or 
m ore t ha n 2 0 sec o n ds) ; ( 5) bl o o d press ure d ecreas e b y m ore t ha n 3 0 m m H g s yst olic or 1 5 m m H g 
diast olic, or if bl o o d press ure dr o ps bel o w 9 0/ 6 0 (if bl o o d press ure n ot alrea d y o utsi de t hese 
ra n ges). 
3. 1. 4.  P ost - P M T A d mi nistr ati o n F oll o w-U p  
F oll o wi n g a s u bject’s fi n al P M T a d mi nistra ti o n, s u bjects e nter t he f oll o w u p p hase. D uri n g t his 
p hase, t he f oll o wi n g will occ ur: ( 1) if s u bjects are i n patie nt, dail y ma xi m u m te m perat ure, 
n u m ber of b o wel m o ve m e nts, a n d a n y e pis o des of e mesis will be rec or de d ( base d o n el ectr o nic 
me dical rec or d) f or  7 cale n dar da ys p ost- F M T; ( 2) i n pre parati o n f or disc h ar ge fr o m t he h os pital, 
s u bjects will rec or d d ail y te m perat ur e, n u m ber of b o wel m o ve me nts, a n d a n y e pis o d es of e mesis 
f or 7 da ys p ost last F M T (all s u bjects will be gi v e n a s y m pt o m diar y car d; a di gital t her m o met er 
will als o be pr o vi de d); ( 3) s u bjects will be c o ntact e d b y t ele p h o ne or i n- pers o n f or a n i nter vie w 
f oc use d o n p ote ntial a d v erse e v e nts at 7 da ys ( or ne xt w or ki n g da y, n ot t o e x cee d 1 0 da ys) after 
fi nal F M T; ( 4) s u bjects will be c o ntacte d b y t ele p h o ne or i n- pers o n at 3 0 da ys ( +/- 3 d a ys) aft er 
fi nal F M T f or a n i nter vie w f oc use d o n p ote ntial a d verse e v e nts; ( 5) s u bjects will be c o ntacte d b y 
tele p h o ne or i n- p ers o n at 5 6 da ys ( +/- 7 d a ys) aft er fi nal F M T f or a n i nter vi e w f oc us e d o n t he 
pri mar y o ut c o me a n d a d verse e v e nts; ( 6) s u bjects will be c o ntacte d b y tele p h o ne or i n - pers o n at 
9 0 da ys ( +/- 7 d a ys) aft er fi nal F M T f or a n i nter vi e w f oc us e d o n p ote ntial a d verse e v e nts; ( 7) 
s u bjects will be c o ntacte d b y tele p h o n e or i n- p ers o n at 1 8 0 da ys ( +/- 7 d a ys ) after fi nal F M T f or 
a n i nter vie w f o c use d o n p ote ntial a d verse e ve nts.  
 
Tele p h o ne vers us i n- pers o n f oll o w- u p will be deter mi ne d base d o n s u bject prefere nce. (If 
s u bjects pref er t o be see n i n pers o n, b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit 
wit h a st u d y tea m me m b er will be arra n ge d).  Su bjects  e nr olle d as o ut patie nts will ha ve at least 
o ne i n- pers o n f oll o w- u p visit sc he d ule d bet wee n 1- a n d 4- w ee ks p ost- F M T. All F M T reci pie nts 
( or t heir s urr o gates) will be gi v e n c o ntact i nf or mati o n f or t he st u d y c o or di n at or. As detaile d 
a b o ve, s u bjects will be f oll o we d f or 1 8 0 da ys f oll o wi n g last i n vesti gati o nal pr o d uct 
a d mi nistrati o n.  All s u bjects will be als o pr o vi de d a st u d y c o ntact tele p h o n e n u m ber o n a c o p y of 
t he i nf or me d c o nse nt f or m, i n case c o ncer ns f or a d verse e v e nt or ot her q u esti o ns arise. S u bjects 
will als o be per mitte d t o i nitiate electr o nic c o m m u nicati o n wit h t he st u d y te a m, alt h o u g h pla n n e d 
f oll o w u p visits will be c o n d ucte d b y tele p h o ne or i n pers o n. T he st u d y tea m ma y reac h o ut t o 
s u bjects electr o nicall y if diffic ulties arise i n reac hi n g t he s u bject b y t ele p h o ne i n or der t o 
sc he d ule visits, b ut st u d y-relate d q u esti o ns will n ot be as ke d electr o nicall y. S u bjects will be 
classifie d as l ost t o f oll o w u p if at least t hree atte m pts are ma de at c o ntact wit h o ut s uccess; 
h o we ver, me di cal r ec or d re vie w will still be use d t o o btai n f oll o w u p i nf or mati o n o n t hese 
s u bjects. If a s u bject is eli gi ble a n d e nr olle d a s ec o n d ( or greater) ti me, t he n t heir s u bse q ue nt 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 6  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
f oll o w u p will be c o n d ucte d acc or di n g t o t he s c he d ule set b y t heir m ost rece nt e nr oll me nt, a n d 
a n y re mai ni n g f oll o w u ps fr o m earlier e nr oll me nt(s) will n ot be perf or me d.  
3. 1. 5.  All oc ati o n t o I nter ve nti o n al Gr o u p  
Stratifie d ra n d o mizati o n will be perf or me d i n a 1: 1 fas hi o n ( o ne t o si n gle-d ose a n d o ne t o d o u ble-
d ose). T he  stratificati o n  will  be  b y  r o ute  of  d eli ver y,  w hic h  will  be  deci de d  o n  f oll o wi n g  
e nr oll me nt b ut pri or t o ra n d o mizati o n.  T h e r o ute of a d mi nistrati o n (i.e., P M T -0 0 1 vers us P M T -
0 0 2 vers us P M T -0 0 3) will be deter mi ne d b y c o u nsel fr o m t he s u bject’s referri n g healt h care 
pr o vi der a n d t h e s u bject’s o w n pref ere n ce.  T h e ra n d o mizati o n strata will i ncl u de: u p per d eli ver y 
( P M T-0 0 2 or P M T -0 0 3) or l o wer deli ver y ( P M T -0 0 1). Stratifie d ra n d o mizati o n b y r o ute will be 
perf or me d  i n  or d er  t o  e ns ure  bala n ce  i n  r o ute  of  d eli ver y  b et wee n  t he  t w o  gr o u ps.  
T he  ra n d o mizati o n sc he d ule will be pre pare d usi n g a ra n d o m-size bl oc k strate g y t o e ns ure bala n ce 
t hr o u g h o ut t he trial. Pri or t o e nr oll me nt of t he first s u bject, a ra n d o mizati o n ta ble will be pr o d uce d 
f or  eac h  cate g or y  usi n g  Stata  statistical  s oft ware a n d  t he  “Rall oc ”  p ac ka ge. T here  is  n o  
ra n d o mizati o n t o a n o-F M T c o ntr ol beca use F M T is alrea d y g ui de li ne-rec o m me n d e d f or t h e 
treat me nt of R- C DI ( M c D o nal d 2 0 1 8).  
3. 2. 
St u dy  E n d p oi nts 
3. 2. 1.  Pri m ar y St u d y E n d p oi nts  
T he pri mar y e n d p oi nt will be pr o p orti o n of s u bjects wit h cli nical res ol uti o n of diarr hea wit h o ut 
rec urre nce i n s u bjects wit h R- C DI at 8 w ee ks ( 5 6 da ys) f oll o wi n g F M T. Cli nical res ol uti o n will 
be defi ne d as f oll o ws:  
•  
≤ 4 st o ols per cale n dar d a y f or t he pri or t w o da ys  wit h n o st o ol of Brist ol st o ol scale t y p e 
7 
•  
N o a d diti o nal st o ol tests wit h a p ositi ve EI A f or C. difficile  t o xi n si nce st u d y e nr oll me nt 
•  
N o a d diti o nal prescri pti o n or use of a nti -C DI a nti bi otics ( u nless gi ve n f or pr o p h yla xis) 
si nce st u d y e nr oll me nt 
•  
N o nee d f or a n a d diti o nal F M T a d mi nistrati o n si nce st u d y e nr oll me nt 
•  
S u bject is ali ve  
3. 2. 2.  Sec o n d ar y St u d y E n d p oi nts  
Sec o n dar y e n d p oi nts i ncl u de: 
•  
All -ca use m ortalit y at 3 0 - a n d 6 0- da ys f oll o wi n g l ast F M T 
•  
C olect o m y or di verti n g il e ost o m y wit hi n 3 0 da ys after last F M T 
•  
C u m ulati ve da ys of h os pitalizati o n fr o m e nr oll me nt u ntil 3 0 da ys after F M T  
•  
C u m ulati ve  da ys i n i nte nsi ve care u nit fr o m e nr oll me nt u ntil 3 0 da ys aft er l ast F M T 
•  
Bact ere mia fr o m e nr oll m e nt u ntil 3 0 da ys after last F M T 
•  
H os pital a d missi o n  wit hi n 6 0 da ys of disc har ge fr o m i n de x h os pitalizati o n 
3. 2. 3.  Pri m ar y S af et y E n d p oi nts  
T he pri mar y safet y e n d p oi nts will i ncl u de:  
•  F re q u e nc y of s olicite d a d verse e v e nts ( A Es) 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 7  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
•  F re q u e nc y of s eri o us a d v erse e v e nts ( S A Es) 
•  F re q u e nc y of A Es of s pecial i nterest ( A E SIs) 
 
See  secti o n 9  f or a d diti o nal details o n a d vers e e ve nt defi niti o ns.   
3. 2. 3. 1.  
P ost -P M T A d mi nistr ati o n m o nit ori n g: Be dsi de f or 6 0 Mi n utes  
Safet y e n d p oi nts f or all r o utes of a d mi nistrati o n will i ncl u de w orse ne d a b d o mi nal pai n, fe ver, 
tac h ycar dia, a n d h y p ote nsi o n (Secti o n 3. 2. 1 ). Safet y e n d p oi nts f or u p p er e nteral deli ver y (i.e., 
P M T - 0 0 2 or P M T- 0 0 3) will i ncl u de e vi de nce of as pirati o n (i ncl u di n g re d uce d o x y ge n s at urati o n, 
tac h y p nea, or res pir at or y distress, as defi ne d a b o ve). 
3. 2. 3. 2.  
P ost -P M T A d mi nistr ati o n F oll o w- U p  
Safet y e n d p oi nts assesse d at t he 7- da y f oll o w- u p a n d all s u bse q ue nt f oll o w- u ps will i ncl u de 
fe ver, di arr h ea, na us ea, a n d v o miti n g. Safet y e n d p oi nts assesse d  at t he 3 0-d a y, 5 6- da y, 9 0- d a y, 
a n d 1 8 0- da y f oll o w- u ps will i ncl u de e vi de nc e of ne w meta b olic diseas e, i ncl u di n g 
h y per gl yce mia, t h yr oi d disease, wei g ht gai n or l oss. 
4.  St u d y P o p ul ati o n a n d D ur ati o n of P artici p ati o n   
4. 1. 
I ncl usi o n Criteri a  
1.  Sec o n d  or greater e pis o de of C DI (first or greater rec urre nce) wit hi n 1 2 m o nt hs, wit h 
s y m pt o ms i ncl u di n g b o w el m o ve me nt altere d i n fre q ue nc y or c o nsiste nc y fr o m baseli ne. 
2.  St o ol p ositi ve f or C. difficile  t o xi n b y EI A or t o xi n ge n e b y N A A T wit hi n 6 0 da ys of 
e nr oll me nt.  
3.  At least o ne a d diti o nal pri or p ositi ve st o ol test f or C. difficile  wit hi n t he pri or 1 2 m o nt hs 
( EI A or N A A T as a b o ve). 
4.  A ge ≥ 1 8 years.  
5.  Mi ni m u m of 7 2 h o urs of recei pt of sta n d ar d-of -care ( va nc o m yci n or fi da x o mici n) 
a nti bi otic treat me nt f or R - C DI pri or t o i nter ve nti o n. 
4. 2. 
E xcl usi o n Criteri a  
1.  E vi de nce of c ol o n/s mall b o wel perf orati o n at t he ti me of st u d y scree ni n g  
2.  G oals of care are dir ecte d t o c o mf ort rat her t ha n c urati ve meas ures.  
3.  M o derate ( A N C < 1 0 0 0 cells/ u L) or se vere ( A N C < 5 0 0 cells/ u L) ne utr o p e nia. 
4.  K n o w n f o o d aller g y t h at c o ul d lea d t o a na p h yl a xis. 
5.  Pre g n a nc y  
a. F or s u bjects of c hil d beari n g p ote ntial (a ges 1 8 t o 5 5), t he s u bject m ust h a ve a 
ne gati ve uri ne pre g n a nc y test wit hi n 4 8 h o urs of c o nse nt a n d n o m ore t ha n 4 8 h o urs 
pri or t o first pr o d uct a d mi nistrati o n 
6.  Meeti n g criteria f or se v er e, se vere -c o m plicate d/f ul mi na nt C DI wit hi n 2 4 h o urs of pla n n e d 
trial e nr oll me nt . We defi ne se vere or se vere-c o m plicate d/f ul mi na nt C DI as a n y o n e of t he 
f oll o wi n g: ( 1) l e u k oc yt osis wit h peri p heral W B C ≥ 1 5, 0 0 0 cells/ m L; ( 2) h y p ote nsi o n wit h 
s yst olic bl o o d press ure s ustai ne d < 9 0 m m H g f or t hree or m ore h o urs or re q uiri n g press ors; 
( 3) pr o vi der d o c u me ntati o n of ile us or ra di ol o gi c e vi de nce of b o w el dilati o n or me gac ol o n; 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 8  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
( 4) ac ute ki d ne y i nj ur y wit h i ncrease i n baseli ne ser u m creati ni ne le vel b y ≥5 0 % or ne w 
dial ysis i nitiati o n; ( 5) ser u m lactate > 2. 2  m m ol/ L;  or  ( 6)  ≥  3  s yste mic  i nfla m mat or y 
res p o nse  s y n dr o me  ( SI R S)  criteria  ( w hic h  i ncl u de  heart  rate  >  9 0  beats  per  mi n ute,  
res pirat or y rate > 2 0 br eat hs per mi n ute or Pa C O 2 < 3 2 m m H g, te m perat ure > 3 8º C or 
< 3 6º C, W B C > 1 2, 0 0 0 cells/ u L, < 4, 0 0 0 cells/ u L, or > 1 0 % i m mat ure ( ba n d) f or ms).   
7.  Recei pt of F M T or e nr oll me nt i n a cli nical trial f or F M T wit hi n t he last  3 m o nt hs. 
4. 3. 
S u bject Recr uit m e nt  
Beca use F M T is rec o m me n de d t her a p y f or R -C DI, p ote ntial s u bjects will be i de ntifie d b y acti ve 
scree ni n g or ref err al fr o m care pr o vi ders wit hi n t he U ni versit y of Pe n ns yl va nia Healt h S yste m 
( Pe n n Me dici ne). P ote ntial s u bjects’ healt h rec or ds will be i nitiall y scree n e d b y a st u d y tea m 
me m ber t o e val uat e if t he i ncl usi o n/e x cl usi o n criteria ma y be  met. If a p ote ntial s u bject ma y 
meet i ncl usi o n/e x cl usi o n criteria, t he p ote ntial s u bj ect ( or t heir d esi g nate d m e dical decisi o n -
ma ker) will be c o ntacte d i n pers o n or b y tele p h o ne t o disc uss partici pati o n. I f a p ote ntial is 
c urre ntl y a d mitte d t o t he h os pital a n d t he pri mar y tea m was n ot t he referri n g tea m, t he st u d y 
tea m will c o ntact t he s u bject’s i n patie nt care tea m t o ascertai n w h et her t he care t ea m has a n y 
o bjecti o n t o t he st u d y tea m e nr olli n g t he p ote ntial s u bject. T he p ote ntial s u bject ( or t heir 
desi g nat e d me dical d ecisi o n -ma ker) will be c o ntacte d t o disc uss partici pati o n . If t he p ote ntial 
s u bject is eli gi ble a n d wa nts t o partici pate, i nf or m e d c o nse nt will be o btai n e d. At t his ti me, 
s u bjects of c hil d beari n g p ote ntial (a ges 1 8 t o 55) will ha ve a uri ne pre g na n c y t est perf or me d. If a 
uri ne pre g n a nc y test is n ot a ble t o be perf or me d or if it is p ositi ve,  t he p ote ntial s u bjects will be 
e x cl u de d.  
4. 4.  
D ur ati o n of St u dy P artici p ati o n 
T he s u bjects will partici p ate i n t he st u d y f or 1 8 0 d a ys ( +/- 7 d a ys) aft er t he last  a d mi nistrati o n of 
t he P M T pr o d uct. St u d y partici pati o n will c o ncl u de wit h t he 1 8 0 - da y f oll o w-u p visit (i n - pers o n 
or b y tel e p h o ne).   
4. 5.  
T ot al N u m ber of S u bjects a n d Sites 
Recr u it me nt will be perf or me d at o ne site wit h  si x partici pati n g Pe n n Me di ci ne U ni versit y of 
Pe n ns yl va nia Healt h S yst e m l ocati o ns: ( 1) t he H os pital of t he U ni versit y of Pe n ns yl va nia ( H U P), 
( 2) Pe n n -Pres b yteria n M e dical Ce nter ( P P M C) , ( 3) Pe n ns yl va ni a H os pital ( P A H), ( 4) La n caster 
Ge ner al H os pital ( L G H), ( 5) C hester C o u nt y H os pital ( C C H), a n d ( 6) Pe n n Me dici ne Pri ncet o n 
Me dical Ce nter ( P M P M C) . E nr oll me nt tar gets 3 0 0 s u bjects.  
4. 6.  
V ul ner a ble P o p ul ati o ns 
C hil dre n, fet uses, or ne o nates ar e n ot i ncl u de d i n t his researc h st u d y b eca use t he gastr oi ntesti nal 
micr o bi o me is si g nifica ntl y diff ere nt bet w ee n c hil dre n a n d a d ults. Pre g n a nt w o me n will n ot be 
eli gi ble t o partici p ate i n t his st u d y d u e t o u n k n o w n ris ks of F M T i n pre g n a nc y. Pris o ners will be 
eli gi ble t o partici p ate i n t his st u d y.  Disa ble d, ec o n o micall y - or e d ucati o nall y- disa d v a nta ge d 
pers o ns will be eli gi ble f or e nr oll me nt. V ul nera ble p o p ulati o ns will be pr otecte d via t he i nf or me d 
c o nse nt pr ocess, w hic h e ns ures t hat e nr olle d s u bjects or s u bject-s urr o gates u n dersta n d st u d y 
ris ks a n d be nefits. V ul nera ble p o p ulati o ns will be pr otecte d fr o m c oerci o n beca use t h ere is n o 
fi na ncial be n efit t o partici pati o n i n t he st u d y. 

 
P M T f or Rec urre nt-C DI  
 
P a ge 1 9  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
5.  St u d y I nter ve nti o n   
5. 1.  
Descri pti o n  
Pe n n Micr o bi o me T her a p y s uite of i n vesti gati o nal pr o d ucts ha ve bee n des cri be d pre vi o usl y i n 
S ecti o n 1. 2 . T he pr o d uct la bel will i ncl u de ( 1) a u ni q ue d ose i de ntifier (a n d barc o de), ( 2) t h e 
P M T f or m ulati o n ( P M T- 0 0 1, P M T- 0 0 2, or P M T- 0 0 3), ( 3) a d o n or i de ntifier, ( 4) t he d ate of 
d o nati o n a n d d ose pr ocessi n g, a n d ( 5) t he e x pirati o n date.  
5. 2. 
I nterve nti o n Re gi m e n  
T his st u d y is  a ra n d o mize d, c o ntr olle d, o pe n la b el trial. S u bjects will be scree ne d t o e v al uate if 
t he y meet i ncl usi o n criteria f or rec urr e nt C DI. If eli gi ble, s u bjects will parti ci pate i n t he i nf or me d 
c o nse nt pr ocess. F oll o wi n g i nf or m e d c o nse nt, t he r o ute of a d mi nistrati o n will be deter mi ne d  b y 
t he a bilit y of t he s u bject t o safel y recei ve oral ca ps ules, i ntra gastric/ d u o de n al/jej u nal i nf usi o n, or 
e ne ma, as d eter mi ne d b y t he s u bject’s treati n g p h ysicia n, a n d b y s u bject prefere n ce. S u bjects 
will t he n be ra n d o mize d t o o ne of tw o  ar ms usi n g stratifie d ra n d o mizati o n b y r o ute of deli ver y: 
( 1) a si n gle a d mi nistrati o n of F M T de v el o pe d fr o m 4 0 g of h u ma n st o ol, w hic h c o ntai ns 1 x 1 0 8 – 
1 x 1 0 1 2 a naer o bic bacterial C F Us (s i n gle d os e), vers us ( 2) t w o a d mi nistrati o ns of t he sa me F M T 
f or m ulati o n a d mi nistere d wit hi n 2 4 h o urs of eac h ot her ( d o u ble d ose). S u bjects ra n d o mize d t o 
recei v e d o u ble- d ose F M T will recei ve t w o d os es fr o m t he sa me d o n or ( b ut n ot necessaril y fr o m 
t he sa me ma n uf act uri n g batc h). If a s u bject is u na ble t o ta ke at least 5 0 % of a d ose, t he y will be 
per mitte d t o o pt t o recei v e a diff ere nt r o ut e of a d mi nistrati o n f or o ne d ose wit hi n 2 4 h o urs. 
S u bjects ra n d o mize d t o t he ar m wit h a d o u ble d os e will recei v e t he sec o n d d ose as l o n g as t he y 
d o n ot ha ve b o wel s ur ger y i n t he i nteri m. S u bjects will be f oll o we d u ntil 1 8 0 da ys after t h eir last 
P M T d ose. A n y a nti bi otics prescri be d as p art of r o uti ne cli nical care f or C DI will be st o p pe d 1 2-
4 8 h o urs (tar get 2 4 h o urs) pri or t o t he i nter ve nti o n. 
5. 3. 
Recei pt  
T he  prescri be d f or m ulati o n of t he i n vesti gati o nal pr o d uct [ P M T- 0 0 1 ( E ne ma), P M T- 0 0 2 
( S us pe nsi o n) or P M T - 0 0 3 (Ca ps ule)] will  be pac k a ge d  o n dr y ice fr o m t he P M T ma n ufact uri n g 
facilit y at t he U ni versit y of Pe n ns yl va ni a. T he ti me of rel ease fr o m fr oze n st ora ge will be 
d oc u me nte d a n d i ncl u d e d i n P M T pr o d uct pac ka gi n g. P M T pr o d ucts will be deli vere d b y st u d y 
staff or c o urier i n si n gle d oses. U p o n recei pt of t h e pr o d uct b y t he I n v esti gat or, pac k a gi n g ( ba gs 
f or P M T- 0 0 1 a n d P M T- 0 0 2; ca ps ule c o ntai ners f or P M T- 0 0 3) will be i ns pecte d f or i nte grit y, a n d 
pr o d uct will be c hec ke d t o e ns ure t hat it is still fr oze n a n d l o g ge d i n t he i n v esti gati o nal pr o d u ct 
acc o u nta bilit y l o g. T h e i n vesti gati o nal pr o d u ct la bel will als o be c hec k e d t o e ns ure t hat t he 
pr o per pr o d u ct is recei ve d, a n d t o e ns ure t hat t he pr o d uct has n ot e x pire d.  
5. 4.  
St or a ge 
I n v esti gati o nal pr o d ucts are tr a ns p orte d fr oze n o n dr y ice b y c o urier or st u d y staff t o t he cli nical 
l ocati o n. I n v esti gati o nal pr o d ucts are tra ns p orte d i n c o ntai ners la b elle d a n d mai ntai ne d at a 
te m perat ur e i n acc or da n ce wit h fe deral a n d l ocal re g ul ati o ns f or t he tra ns p ort of bi ol o gical 
pr o d ucts. 
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 0  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
At t he cli nical l ocati o n , a d mi nistrati o n of P M T - 0 0 1 or P M T - 0 0 2 will be i nitiate d wit hi n 1 8 0 t otal 
mi n utes of pr o d uct releas e fr o m fr oze n st ora ge. At t he cli nical site, a d mi nistrati o n of P M T- 0 0 3 
will be i nitiate d wit hi n 1 2 0 mi n utes of pr o d uct rel ease fr o m fr oze n st ora ge. T he ti me of  release 
fr o m fr oze n st ora ge will be i ncl u de d i n P M T pr o d uct pac ka gi n g (Secti o n 5. 3 ). 
 
P M T - 0 0 1 a n d P M T- 0 0 2 d oses will be t ha we d at r o o m te m perat ure f or 3 0- 6 0 mi n utes pri or t o 
a d mi nistrati o n. T he ba g ma y b e massa ge d d uri n g t ha wi n g. P M T - 0 0 3 will re mai n o n dr y ice u ntil 
t he ti me of a d mi nistrati o n. 
 
A n y d os es release d fr o m fr oze n st ora ge b ut n ot a d mi nistere d wit hi n t he all otte d ti me ( 1 8 0 
mi n utes f or P M T- 0 0 1 a n d P M T- 0 0 2, 1 2 0 mi n utes f or P M T- 0 0 3) after release (e. g., d ue t o d ela ys 
i n tra ns p ort) will be destr o ye d. I n s uc h cases, eli gi ble s u bjects will be offere d a n ot her d os e, a n d 
t he releas e pr ocess will be re-i nitiate d.  
5. 5.  
Pre p ar ati o n a n d P ac k a gi n g 
Pre parati o n of t he t hree i n vesti gati o nal pr o d u cts [ P M T- 0 0 1 ( E ne ma), P M T- 0 0 2 ( S us pe nsi o n) a n d 
P M T -0 0 3 ( Ca ps ule)] will be perf or me d at t he P M T ma n ufact uri n g facilit y at t he U ni versit y of 
Pe n ns yl va nia.  P M T - 0 0 1 a n d P M T- 0 0 2 are p ac k a ge d i n E V A ba gs s uita ble f or st ora ge at  
< - 7 0° C (tar get - 8 0° C). P M T- 0 0 3 is e nca ps ulate d wit hi n t hree neste d gel ati n ca ps ules (sizes 0 0, 
0, a n d 1), t he n pac ka ge d i n a n H D P E ca ps ule c o ntai ner s uita ble f or st ora ge at < - 7 0° C (tar get  
- 8 0° C). T he t hree i n vesti gati o nal pr o d u cts will be pac ka ge d i n si n gle d os es. 
5. 6. 
Bli n di n g  
Neit her s u bjects  n or i n v esti gat ors will  be bli n de d. 
5. 7. 
A d mi nistr ati o n a n d Acc o u nt a bility    
T he i n vesti gati o nal pr o d ucts will be c hec k e d o n recei pt as a b o v e ( Secti o n 5. 3 ). Pri or t o 
a d mi nistrati o n, P M T - 0 0 1 a n d P M T- 0 0 2 will be all o we d t o t ha w at r o o m te m perat ure ( 5 0° F - 
7 5 ° F) f or 3 0- 6 0 mi n utes. A d mi nistrati o n of P M T - 0 0 1 a n d P M T- 0 0 2 will be gi n wit hi n  6 0 
mi n utes of t ha wi n g. Pri or t o a d mi nistrati o n, P M T - 0 0 3 will be ke pt o n dr y i ce; P M T- 0 0 3 will n ot 
be t ha we d b ef or e a d mi nistrati o n.  
 
As state d i n Secti o n 5. 4 , t he t otal ti me fr o m releas e fr o m fr oze n st ora ge at t he ma n ufact uri n g 
facilit y t o i nitiati o n of a d mi nistrati o n will n ot e x cee d 1 8 0 mi n utes f or P M T- 0 0 1 a n d P M T- 0 0 2; it 
will n ot e x cee d 1 2 0 mi n utes f or P M T - 0 0 3.  
 
T he d urati o n of a d mi nistrati o n will ta ke 1 0 - 9 0 (t ar get 3 0) mi n utes f or all pr o d ucts. 
A d mi nistrati o n  of all t hree P M T pr o d ucts will be perf or me d b y a lice ns e d p h ysicia n, a d va nce d 
me dical practiti o ner, or n urse. 
 
P M T -0 0 1 will be a d mi nistere d b y e n e ma  usi n g a n a p pr o ve d e n e ma a d mi nistrati o n kit. P M T- 0 0 2 
will be a d mi nistere d via i ntra gastric , i ntra d u o d e nal, or i ntrajej u nal r o ute, c o nti n ge nt o n t he 
prese nce of a pre -e xisti n g a p pr o ve d i ntra gastric , i ntra d u o de nal, or i ntrajej u nal t u be. P M T- 0 0 3 
will be a d mi nistere d orall y. P ost- pr oce d ure m o nit ori n g will be perf or m e d  as descri be d 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 1  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
else w her e. F or eac h i n vesti gati o nal pr o d uct d ose, t he pr o d uct i de ntit y, d os e tar gete d f or 
a d mi nistrati o n , t he date a n d ti me a d mi nistere d, r o ute of a d mi nistrati o n, s u bject i de ntit y, q ua ntit y 
of pr o d uct act uall y a d mi nistere d, a n d q ua ntit y of pr o d uct re mai ni n g will b e rec or de d via a 
sta n dar d f or m. 
5. 8. 
S u bject C o m pli a nce M o nit ori n g  
P ost- pr oce d ure m o nit ori n g will be perf or me d  as descri be d else w here  (Secti o ns 3. 1. 3  t o 
Secti o n  3. 1. 4 ). F or eac h i n vesti gati o nal pr o d u ct d ose, t he pr o d uct i de ntit y, d ose tar gete d f or 
a d mi nistrati o n, t he date a n d ti me a d mi nistere d, r o ute of a d mi nistrati o n, s u bject i de ntit y, q ua ntit y 
of pr o d uct act uall y a d mi nistere d, a n d q ua ntit y of pr o d uct re mai ni n g will b e rec or de d via a 
sta n dar d f or m. T h e st u d y tea m  will rec or d if t h e s u bject was n ot a ble t o t ol erate or recei ve t he 
f ull d ose d ue t o a d vers e e ve nts or beca use t he all o we d d urati o n of a d mi nistr ati o n was e x cee d e d.  
5. 9. 
Ret ur n or Destr ucti o n of I nvesti g ati o n al Pr o d uct  
F or P M T - 0 0 1 or P M T- 0 0 2, t he v ol u me of i n vesti gati o nal pr o d u ct will be rec or de d at t he ti me of 
dr u g pr o d uct ma n uf act uri n g, a n d t h e v ol u me of resi d ual i n vesti gati o nal pr o d uct (if a n y) will be 
rec or d e d b y t he lice ns e d me dical pr of essi o nal perf or mi n g a d mi nistrati o n aft er a d mi nistrati o n is 
c o m plete d ( or st o p pe d). F or P M T - 0 0 3, t he n u m ber of ca ps ules i n t he d os e will be rec or d e d at t he 
ti me of dr u g pr o d uct ma n ufact uri n g, a n d t h e n u m ber of remai ni n g ca ps ules (if a n y) will be 
rec or d e d b y t he lice ns e d me dical pr of essi o nal perf or mi n g a d mi nistrati o n aft er a d mi nistrati o n is 
c o m plete d ( or st o p pe d). A n y re mai ni n g i n vesti gati o nal pr o d uct will be dis p ose d of at t he cli nical 
site. 
6.  St u d y Pr oce d ures  
T he st u d y pr oce d ures are als o o utli ne d i n detail bel o w. T he sc he d ule of st u d y pr o ce d ures is 
prese nte d  i n Ta bl e 2 .  
6. 1. 
Scree ni n g a n d E nr oll m e nt   
6. 1. 1.  S ur veill a nce Test Re vie w  
P ote ntial  s u bjects  will  be  i de ntifie d  b y  acti ve  scree ni n g  or  referral  f or  F M T  treat me nt  at  
partici pati n g st u d y sites . 
6. 1. 2.  Me dic al Rec o r d Re vie w f or I ncl usi o n/ E xcl usi o n Criteri a  
Referr al f or F M T treat me nt will pr o m pt re vie w  of t he electr o nic healt h  rec or d  t o  deter mi ne 
w het her a p ot e ntial s u bject ma y m eet i ncl usi o n/e x cl usi o n criteria  (Secti o ns 4. 1  a n d 4. 2 ). 
6. 1. 3.  I nf or me d C o nse nt 
If  a  p ote ntial  s u bject  m a y meet  i ncl usi o n/e x cl usi o n  criteria,  t he  st u d y tea m  will  c o ntact  t he  
p ote ntial s u bject ( or t heir desi g n ate d m e dical d ecisi o n-ma ker)  t o disc uss partici pati o n. If t he 
p ote ntial s u bject is eli gi ble a n d w a nts t o partici p ate , i nf or me d c o nse nt will be o btai ne d.  Su bjects  
o f c hil d beari n g p ot e ntial will be teste d usi n g a uri ne pre g n a nc y test if p ossi ble; if uri ne pre g na nc y 
test p ositi ve or n o t p ossi ble, p ote ntial s u bjects will be e x cl u de d . A rec or d of all scree ne d s u bjects 
will be mai ntai ne d t o e val uate t he fr e q ue nc y of i de ntifie d e x cl usi o ns or care- tea m o bjecti o ns. 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 2  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 1. 4.  Decisi o n o n M o de of Deli ver y  
T he e nr olle d s u bject  will be offere d P M T -0 0 1, P M T -0 0 2, or P M T -0 0 3, s o l o n g as t he e nr olle d 
s u bject a n d t heir ref erri n g care pr o vi der dee m t he m o des of deli ver y safe. T he decisi o n o n m o de 
of deli ver y will be det er mi ne d b y s u bject prefere nce . 
6. 1. 5.  R a n d o miz ati o n 
F oll o wi n g e nr oll me nt  a n d t he s u bject’s decisi o n o n  m o de of deli ver y, stratifie d  ra n d o mizati o n will 
be perf or me d as p er Secti o n 3. 1. 5 . 
6. 2. 
St u dy I nterve nti o n P h ase  
6. 2. 1.  P M T Pr o d uct Recei pt  
After t h e tr eat me nt pla n is deter mi ne d b y ra n d o mizati o n, t he P M T pr o d uct t o w hic h t he s u bjects 
is assi g ne d will be pr e par e d a n d recei ve d as descri be d a b o ve ( Secti o n s 5. 2  - 5. 7 ). 
6. 2. 2.  A d mi nistr ati o n  
D uri n g t he i nter ve nti o n peri o d, f oll o wi n g i nf or me d c o nse nt  a n d ra n d o mizati o n, s u bjects will 
recei v e eit her ( 1) si n gl e-d ose P M T a d mi nistrati o n al o ne, or ( 2) o n e -d os e P M T a d mi nistrati o n 
f oll o we d  b y  a  sec o n d  d ose  wit hi n  2 4  h o urs ( wit h  at  least  4  h o urs  se parati n g  d oses).  Eac h  
ad mi nistrati o n of t he pr o d uct ( P M T-0 0 1, P M T -0 0 2, or P M T - 0 0 3) will ta ke place o ver 1 0 t o 9 0 
mi n utes (tar get 3 0 mi n utes). A nti bi otics prescri be d as p art of r o uti ne cli nical care f or C DI will be 
st o p pe d 1 2- 4 8 h o urs (tar get 2 4 h o urs) pri or t o t he i nter ve nti o n. 
6. 2. 3.  P ost -I nter v e nti o n 6 0 mi n utes 
S u bjects  will  be  m o nit ore d  f or  a  peri o d  of  6 0  mi n utes  f oll o wi n g  c o m pleti o n  of  eac h P M T 
a d mi nist rati o n. S u bjects will be vis uall y o bs er v e d f or si g ns of as pirati o n or ot her res pirat or y 
distress, a b d o mi nal pai n, v o miti n g, ot her si g ns of aller gic reacti o n, a n d c ha n ges i n vital si g ns. Vital 
si g ns (t e m perat ure, h eart rate, res pir at or y rate, bl o o d press ure, a n d o x y ge n sat urati o n) will be 
c hec k e d i m me diatel y p ost -a d mi nistrati o n a n d at 3 0 a n d 6 0 mi n utes f oll o wi n g c o m pleti o n of P M T 
a d mi nistrati o n. T he f oll o wi n g vital si g n c ha n ges will be rec or de d if o bser ve d, a n d will pr o m pt 
n otificati o n of t he pri mar y cli nica l care t ea m: ( 1) i ncreas e or d ecreas e b y greater t h a n or e q ual t o 
3 0 beats per mi n ute; ( 2) r es pirat or y r ate i ncrease or decrease b y greater t ha n or e q ual t o 1 0 breat hs 
per mi n ute or if res pir at or y rate dr o ps b el o w 1 0 or i ncreas es a b o ve 2 5 (if res pirat or y r ate n ot 
alrea d y o utsi de t hes e ra n ges); ( 3) te m perat ure: i ncreas e or decrease b y greater t ha n or e q ual t o 2 
de grees Fa hre n h eit, or if te m perat ur e dr o ps bel o w 9 6 °F or i ncreases a b o ve 1 0 0. 4 °F (if te m perat ure 
n ot alrea d y o utsi de t hes e ra n ges); ( 4) o x y ge n sat ur ati o n decreas e b y greater t ha n or e q u al t o 5 % 
(s ustai ne d f or m ore t ha n 2 0 sec o n ds) or if o x y ge n sat urati o n dr o ps b el o w 9 0 % ( o n c urre nt a m o u nt 
of o x y ge n deli ver e d, s ustai ne d f or m ore t ha n 2 0 sec o n ds); ( 5) bl o o d press ure decrease b y m ore 
t ha n 3 0 m m H g s yst olic or 1 5 m m H g di ast olic, or if bl o o d press ure dr o ps bel o w 9 0/ 6 0 (if bl o o d 
press ure n ot alrea d y o utsi de t hese ra n ges).  

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 3  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 3. 
St u dy F oll o w - u p P h ase  
6. 3. 1.  F oll o w- u p 7 d a ys 
F oll o wi n g a s u bject’s fi nal P M T a d mi nistrati o n, s u bjects e nter t he f oll o w u p p hase. D uri n g t his 
p hase, vital si g ns, s y m pt o ms, a n d la b orat or y v al ues s u g gesti ve of a d v erse e ve nts will be trac k e d 
a n d rec or de d. S pecifi call y, w hile r e mai ni n g i n p atie nt, dail y ma xi m u m te m perat ure, n u m ber of 
b o wel m o ve me nts, a n d a n y e pis o des of e mesis will be rec or de d ( base d  o n electr o nic me dical 
rec or d) f or 7 cale n dar da ys  p ost-F M T.  I n pre parati o n f or disc har ge, s u bjects will be gi ve n a diar y 
f or tr ac ki n g d ail y t e m per at ure, n u m ber of b o wel m o ve me nts, a n d a n y e pis o des of e mesis f or 7 da ys 
p ost last F M T (all s u bjects will be gi ve n a s y m pt o m diar y car d; a di gital t her m o meter will als o be 
pr o vi de d). S u bjects will be c o ntacte d b y t ele p h o ne or i n -pers o n f or a n i nter vie w f oc us e d o n 
p ote ntial a d verse e ve nts at 7 da ys aft er fi nal F M T; t he first atte m pt at c o nt act will be ma de b y t h e 
first w or ki n g da y at 7 da ys or later ( n ot t o e x cee d 1 0 da ys) f oll o wi n g t he fi nal F M T. (I n case of 
tele p h o ne f oll o w-u p, t he 7 -da y s y m pt o m diar y car d will be tra nscri be d b y st u d y staff o v er t he 
p h o ne /a n d or c ollecte d d uri n g t he i n-pers o n f oll o w -u p visit.  See  Secti o n 6. 3. 2 ). Tele p h o ne vers us 
i n-pers o n f oll o w -u p will be deter mi ne d b ase d o n s u bject prefere nce. If s u bj ects prefer t o b e see n 
i n pers o n, b ut ha v e b ee n disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y tea m me m ber will 
be arr a n ge d.  
 
T o a d dress t he e x pl orat or y ai ms, if bl o o d t hat was c ollecte d f or cli nical p ur p oses w o ul d ot her wise 
be discar d e d, it will be ca pt ure d f or i m m u ne res p o nse p he n ot y pi n g.  Bl o o d will be c ollecte d fr o m 
resi d ual materi al a vaila ble i n E D T A (“ p ur ple t o p”) vac utai ner t u b es alrea d y c ollecte d i n t he 
cli nical la b orat or y. If n o resi d ual bl o o d is a vaila ble, or if s u bjects are o ut patie nts or ha ve bee n 
disc har ge d fr o m t he h os pital, n o bl o o d will be c oll ecte d. B l o o d s p eci me n a n al ysis will be directe d 
b y t he pri n ci pal i n vesti gat or a n d st u d y tea m.  
6. 3. 2.  F oll o w- u p 3 0 d a ys 
S u bjects will be c o ntacte d a gai n b y tel e p h o ne or i n- pers o n at 3 0 da ys ( +/- 3 da ys) aft er fi nal F M T 
f or a n i nter vie w f oc us e d o n p ote ntial a d verse e ve nts. Tele p h o ne vers us i n -pers o n f oll o w -u p will 
be deter mi ne d b ase d o n s u bject pref er e nce.  S u bjects e nr olle d as o ut patie nts  will ha ve at least o n e 
i n-pers o n f oll o w -u p visit sc he d ule d b et wee n 1 - a n d 4 wee ks p ost -F M T.  (If s u bjects prefer to be 
see n i n pers o n, b ut ha v e b ee n disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y tea m me m ber 
will be arra n ge d).   
6. 3. 3.  F oll o w- u p 5 6 d a ys 
S u bjects will be c o ntacte d  b y tele p h o n e or i n -pers o n at 5 6  da ys ( +/ - 7 d a ys) after fi n al F M T f or a n 
i nter vie w f o cuse d o n t he pri mar y o utc o me a n d p ote ntial a d vers e e v e nts . Tele p h o ne vers us i n -
pers o n f oll o w -u p will be deter mi ne d bas e d o n s u bj ect prefere nce. (If s u bjects prefer t o be s ee n i n 
pers o n, b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y  tea m me m ber will 
be arr a n ge d).  
6. 3. 4.  F oll o w- u p 9 0 d a ys 
S u bjects will be c o ntacte d b y tele p h o n e or i n -pers o n at 9 0 da ys ( +/ - 7 d a ys) after fi n al F M T f or a n 
i nter vie w f o c use d o n p ote ntial a d vers e e v e nts. Tele p h o ne v ers us i n -p ers o n f oll o w -u p will be 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 4  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
deter mi ne d base d o n s u bject pref ere n ce. (If s u bjects prefer t o be see n i n pers o n, b ut ha ve bee n 
disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y tea m me m b er will be arra n ge d).  
6. 3. 5.  E n d - of-st u d y visit at 1 8 0 d a ys  
T he  st u d y will  c o ncl u d e  after  s u bjects  are  c o ntacte d  b y tele p h o n e  or  i n -pers o n  at  1 8 0  d a ys  
( +/- 1 0 da ys) after fi nal F M T f or a  fi nal i nter vie w f oc use d o n p ote ntial a d verse e ve nts. Tele p h o n e 
vers us i n -pers o n f oll o w -u p will be deter mi ne d base d o n s u bject prefere nce. (If s u bjects prefer t o 
be see n i n pers o n,  b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y tea m 
me m ber will be arra n ge d).  
 
S u bjects will be per mitte d t o i nitiate electr o nic c o m m u nicati o n wit h t he st u d y tea m, alt h o u g h 
pla n ne d f oll o w u p visits will be c o n d ucte d b y tele p h o ne or i n pers o n. T h e st u d y tea m ma y reac h 
o ut t o s u bjects electr o nicall y if diffi c ulties arise i n reac hi n g t he s u bj ect b y t ele p h o ne i n or der t o 
sc he d ule visits, b ut st u d y-relate d q u esti o ns will n ot be as ke d electr o nicall y. S u bjects will be 
classifie d as l ost t o f oll o w u p if at least t hree atte m pts are ma de at c o ntact wit h o ut s uccess; 
h o we ver, me di cal r ec or d re vie w will still be use d t o o btai n f oll o w u p i nf or mati o n o n t hese 
s u bjects. If a s u bject is eli gi ble a n d e nr olle d a s ec o n d ( or greater) ti me, t he n t heir s ubse q ue nt 
f oll o w u p will be c o n d ucte d acc or di n g t o t he s c he d ule set b y t heir m ost rece nt e nr oll me nt, a n d 
a n y re mai ni n g f oll o w u ps fr o m earlier e nr oll me nt(s) will n ot be perf or me d.  
 
6. 4. 
Resc ue T her a py  
If a s u bject is t h o u g ht t o ha ve a se ver e a d verse e v e nt it will be rec or de d b y t he st u d y tea m a n d t he 
s u bject will be f oll o we d u ntil res ol uti o n a n d referre d t o s u bject’s pri mar y cli nical care tea m. I n t he 
case of a n i na de q u ate cli nical res p o ns e , t he s u bj ect’s pri mar y cli nical care tea m will be c o ntact e d,  
s o t hat t he s u bject ca n p urs ue treat me nt at t heir discreti o n. Re gar dless of resc ue t hera p y  use d, 
s u bjects will c o nti n ue t o be f oll o we d u ntil t he e n d of t he st u d y. 
6. 5. 
U nsc he d ule d Visits  
Data c ollecte d fr o m s u bjects w h o c o ntact  t he st u d y tea m ( b y tele p h o n e, electr o nicall y, or i n -
pers o n) o utsi de of t he sc h e d ule d visits (as a b o ve) will be ass ociate d wit h t he ne xt sc he d ule d st u d y 
visit, as eac h st u d y visit is i nte n de d t o retr os pecti vel y c o ver t he ti me p eri o d si nce t h e last st u d y 
visit.   
6. 6. 
S u bject Wit h dr a w al  
S u bje cts ma y wit h dra w fr o m t he st u d y at a n y ti me wit h o ut i m pact t o t heir re g ular me dical care, 
b ut  t he y  will  recei ve  n o  f urt her  tr eat me nt  wit h  i n vesti gati o nal  pr o d u ct .  T he y  ma y  als o  be  
disc o nti n ue d  fr o m  t h e  st u d y  at  t he dis creti o n  of  t he  I n ves ti gat or  f or  lac k  of  a d h ere n ce  t o  
i nter ve nti o n or st u d y pr o ce d ures or visit sc he d ules, a d verse e v e nt s, or d ue t o ot her c o ncer ns. T h e 
I n v esti gat or or t he S p o ns or ma y wit h dra w s u bjects w h o vi olate t he st u d y pla n, or t o pr otect t he 
s u bject f or r eas o ns of s af et y or f or a d mi nistrati ve reas o ns.  It will be d o c u me nte d w het her or n ot 
eac h  s u bject  c o m pletes  t he  cli nical  st u d y.  T h e  tar gete d  st u d y  e nr oll me nt  is  3 0 0 s u bjects 
ra n d o mize d; s u bjects w h o wit h dra wal after ra n d o mizati o n will n ot be re place d. 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 5  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 6. 1.  D at a C ollecti o n  
Data will be o btai ne d fr o m direct s u bject o bser v ati o n, re vie w of t he s u bject’s electr o nic me dical 
rec or d, sc h e d ule d a n d u nsc he d ule d f oll o w-u p visits ( w hic h ma y be i n -p ers o n or b y t ele p h o ne), as 
detaile d a b o ve. F or s u bjects w h o wit h dra w c o nse nt t o partici pate i n t he st u d y, dat a c ollect e d u p 
u ntil t he ti me of wit h dra wal will be ke pt, b ut n o f urt her data will be c ollect e d.  
6. 6. 2.  E arl y Ter mi n ati o n Visits   
If t he s u bject deci d es t o wit h dra w fr o m t he st u d y after ra n d o mizati o n, t he s u bject will be as ke d t o 
c o m plete all f oll o w- u p acti vities t hat w o ul d ha ve bee n perf or me d at t he n e xt sc he d ule d f oll o w-u p 
visit .  

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 7  of  4 1  
 
P M T f or Rec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
 
7.  St u d y E v al u ati o ns a n d Me as ure me nts  
7. 1. 
Me dic al Rec or d Revie w  
T he me dical r ec or d will be re vie w e d pri or t o e nr oll me nt, i n or der t o assess eli gi bilit y, as o utli ne d 
a b o ve. T he me di cal rec or d will be re vie we d at 7 - d a y, 3 0- da y, 5 6-d a y, 9 0- d a y, a n d 1 8 0- d a y 
f oll o w- u ps t o hel p ascertai n pri mar y a n d sec o n dar y o utc o mes, as well as a d verse e v e nts  
(Secti o ns 3. 2  a n d 9. 1. 3 ). HI P A A a ut h orizati o n will be o btai ne d wit h i nf or m e d c o nse nt. 
7. 2.  
P hysic al E x a mi n ati o n 
P h ysical e x a mi nati o n will i ncl u de o nl y of vital si g n meas ure me nts, as b el o w.  
7. 3. 
Vit al Si g ns  
Vital si g ns will be c hec k e d b y st u d y tea m pers o n n el d uri n g t he 6 0 mi n ute o bser vati o n peri o d 
after pr o d u ct a d mi nistrati o n. Para meters f or n otif yi n g t he cli nical care tea m of a b n or malities are 
o utli ne d i n t he st u d y i nter ve nti o n p hase secti o n a b o ve. Vital si g ns will be c hec ke d w hile s u bjects 
are eit her sitti n g or l yi n g d o w n, as per t heir prefere nce.  
7. 4.  
L a b or at ory Ev al u ati o ns 
N o la b orat or y e val uati o ns will be perf or me d as a part of t his st u d y. L a b orat or y val u es will be 
c ollecte d fr o m re vie w of t he s u bject’s electr o nic me dical rec or d, i n or der t o ascert ai n o utc o me 
data  a n d a d v erse e ve nts, as descri be d a b o ve.   
7. 5. 
Pre g n a ncy Testi n g  
Uri ne p re g n a nc y testi n g usi n g a n F D A- cleare d test will be perf or me d as a p art of t his st u d y.  
7. 6. 
Ot her Ev al u ati o ns, Me as ures  
S u bjects w h o are disc h ar ge d fr o m t he h os pital pri or t o 7 da ys f oll o wi n g t h eir last F M T will be 
pr o vi de d wit h a diar y a n d t her m o meter t o kee p trac k of t heir t e m perat ure ( o nce a d a y), st o ol 
fre q ue n c y, an d a n y e mesis. T his diar y will be re vie we d wit h s u bjects at t heir 7- da y f oll o w- u p 
visit.   
 
F or t he e x pl orat or y ai m, i m m u ne p he n ot y pic a nal ysis usi n g fl o w c yt o metr y ma y b e perf or me d 
o n a s u bset of s u bjects usi n g w h ole bl o o d c ollecte d f or cli nical p ur p os es, w hic h w o ul d ot her wise 
be discar d e d.  Bl o o d will be c ollecte d fr o m resi d u al material a vaila ble i n E D T A (“ p ur ple t o p”) 
vac utai ner t u b es alrea d y c ollecte d i n t he cli nical l a b orat or y.  
7. 7. 
Effic acy Ev al u ati o ns  
T he pri mar y o utc o me (ti me t o res ol uti o n of R- C DI s y m pt o ms)  will be assesse d at 8 wee ks ( 5 6 
da ys) f oll o wi n g t he i nter ve nti o n. T he criteri a will be assesse d via p atie nt i nter vie w a n d electr o nic 
me dical rec or d r e vie w as per Secti o n 3. 2. 1 . 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 8  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
7. 8. 
Ge netic Testi n g ( o nl y if a p plic a ble) 
N o h u ma n ge netic testi n g will be perf or me d. F or t he e x pl orat or y ai m, st o ol micr o bi o me a nal ysis 
will be perf or me d o n st o ol sa m ples o btai ne d as descri be d i n Secti o n 7. 6 . T hese st o ol sa m ples 
w o ul d ot her wise be discar de d. T his will i n v ol ve se q ue nci n g of micr o bial n u cleic aci ds. T his will 
n ot i n v ol ve h u ma n D N A se q ue nci n g a n d t h us d oes n ot c o m prise ge netic testi n g. Li ke wise, 
p he n ot y pi n g of i m m u ne r es p o nse via fl o w c yt o metr y ma y b e perf or me d o n a s u bset of s u bjects, 
usi n g w h ole bl o o d c ollecte d f or cli nical p ur p os es t hat w o ul d ot he r wise be discar de d. T his will 
n ot i n v ol ve h u ma n D N A se q ue nci n g a n d or  ge neti c testi n g.  
7. 9. S afety Ev al u ati o ns 
7. 9. 1.  De vi ati o ns a n d E xc e pti o ns  
E xce pti o n  ( Pr os pecti ve acti o n): 
A n e xce pti o n  is defi ne d as a o ne-ti me, i nte nti o nal acti o n or pr ocess t hat de parts fr o m t he 
a p pr o ve d st u d y pr ot oc ol, i nte n de d f or o ne o cc urre nce.  If t h e acti o n disr u pts t he st u d y pr o gress, 
s uc h t hat t he st u d y d esi g n or o utc o mes ma y be c o m pr o mise d, or t he acti o n c o m pr o mises t he 
safet y a n d/ or welfare of st u d y s u bjects, a d v a nce d oc u me nte d a p pr o v al fr o m t he Re g ulat or y 
S p o ns or a n d l ocal re g ulat or y re vie w c o m mittees, per i nstit uti o nal g ui deli nes, is re q uire d.  
A p pr o val fr o m t he Re g ul at or y S p o ns or m ust be recei ve d pri or t o s u b missi o n t o t he l ocal 
re g ulat or y re vie w c o m mittees. 
 
De vi ati o n  ( Retr os pecti ve acti o n): 
A devi ati o n is defi ne d as a o ne-ti me, u ni nte nti o nal acti o n or pr ocess t hat de parts fr o m t he 
a p pr o ve d st u d y pr ot oc ol, i n v ol vi n g o ne i nci de nt a n d i de ntifie d retr os pecti vel y.  If t h e de viati o n 
disr u pts st u d y pr o gress, s uc h t hat t he st u d y d esi g n or o utc o mes ma y be c o m pr o mise d, or t he 
de viati o n c o m pr o mises t he safet y a n d/ or welfare of st u d y s u bjects, t he de viati o n m ust be 
re p orte d t o t he Re g ulat or y S p o ns or wit hi n 2 da ys of PI k n o wl e d ge a n d t o l ocal re g ulat or y re vie w 
c o m mittees per i nstit uti o nal g ui deli nes.  
Re p ort t he f oll o wi n g i nf or mati o n o n t he S p o ns or’s e x ce pti o n/ de viati o n f or m:  
•  Pr ot oc ol n u m ber 
•  S u bject n u m ber 
•  Descri pti o n of t he e x ce pti o n or de viati o n 
•  I m pact o n s u bject safet y 
•  I m pact o n data i nte grit y  
De viati o ns t hat are assesse d b y t h e PI t o n ot disr u pt t he st u d y pr o gress, s uc h as n ot affecti n g t h e 
st u d y desi g n or o utc o me, or c o m pr o misi n g t he s afet y a n d/ or welfare of st u d y s u bjects, s h o ul d be 
d oc u me nte d i n site rec or ds a n d c o ntai n d oc u me nt ati o n of t he PI’s assess m e nt. 
7. 9. 2.  S af et y P ar a met ers  
Safet y will be m o nit ore d i n se veral w a ys:  
•  
3 0- a n d 6 0- mi n ute  o bser vati o ns wit h vital si g n c h ec ks aft er i n vesti gati o nal pr o d uct 
a d mi nistrati o n . 

 
P M T f or Rec urre nt-C DI  
 
P a ge 2 9  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
•  
F oll o w- u p at 7 da ys, 3 0 d a ys, 9 0 d a ys, a n d 1 8 0 da ys as o utli ne d i n t he sc h e d ule of st u d y 
pr oce d ur es  (Ta bl e 1 ). 
•  
E x a mi nati o n of safet y -rel ate d sec o n d ar y o utc o mes , i ncl u di n g: bact ere mia, m ortalit y, 
h os pital a d missi o n, c olect o m y or di verti n g ile ost o m y . 
8.  St atistic al Pl a n  
8. 1.  
Pri m ary E n d p oi nt 
T he pri mar y e n d p oi nt will be pr o p orti o n of s u bjects wit h cli nical res ol uti o n of diarr hea wit h o ut 
rec urre nce i n s u bjects wit h R-C DI at 8 wee ks ( 5 6 da ys) f oll o wi n g F M T . T o a d dress t he p ote ntial 
f or misclassificati o n of s u bjects w h o are o nl y N A A T-p ositi ve f or C.  difficile  ( Mc D o n al d 2 0 1 8), 
the pri mar y a n al ysis will be stratifie d b as e d o n t h e m ost rece nt p ositi ve C DI test ( N A A T vers us 
EI A) pri or t o e nr oll me nt. 
8. 2.  
Sec o n d ary E n d p oi nts  
Sec o n dar y e n d p oi nts  ar e detaile d i n Secti o n 3. 2. 2 . Sec o n dar y e n d p oi nts will i ncl u de   all-ca us e 
m ortalit y ( 3 0- a n d 6 0-da ys f oll o wi n g last F M T ), colect o m y or di verti n g ile ost o m y wit hi n 3 0 da ys 
after last F M T , c u m ulati ve da ys of h os pitalizati o n fr o m e nr oll me nt u ntil 3 0 da ys aft er F M T, 
cu m ulati ve da ys i n i nte nsi ve care u nit fr o m e nr oll me nt u ntil 3 0 da ys after last F M T , bactere mia 
fr o m e nr oll me nt u ntil 3 0 da ys after l ast F M T, h os pital a d missi o n wit hi n 6 0 da ys of i nter ve nti o n. 
8. 3.  
S a m ple Size a n d P o wer Deter mi n ati o n 
T he pri mar y a n al ysis will be stratifie d base d o n t h e m ost rece nt p ositi ve C DI test ( N A A T v ers us 
EI A) pri or t o e nr oll me nt. Gi ve n t he a ntici pate d e nr oll me nt of 3 0 0 s u bjects ( 1 5 0 per i nter v e nti o n 
gr o u p),  a c ons er vati ve esti mate t hat 1 0 % of s u bjects will be l ost t o f oll o w - u p (i.e., mi ni m u m 
s u bject n u m ber 9 0 % of t otal), a n d t he e x pectati o n t hat t he rati o of EI A -p ositi ve/ N A A T - p ositi ve 
s u bjects will be 1: 2, t he e x pecte d sa m ple size will be 9 0 f or EI A a n d 1 8 0 f or NA A T 
( 1 5 0 * 0. 9 = 1 3 5 per ar m, wit h a 4 5: 9 0 rati o f or EI A/ N A A T). T h e l o w -d ose c ure rat e is a ntici pate d 
t o be a b o ut 5 0 % i n t he N A A T gr o u p a n d 7 0 % i n t he EI A gr o u p. Bas e d o n t hese ass u m pti o ns, t he 
detecta ble differ e nce  bet wee n t he c ure rates f or t he l o w a n d hi g h d ose gr o u ps f or 8 0 % p o wer a n d 
var yi n g t y p e I err o r rates, base d o n a C hi-s q uare test (t w o-si de d), are pr o vi d e d bel o w. 
 
Str atifie d 
P o p ul ati o n  
N u m ber  of 
s u bjects (s u bjects 
per ar m)  
T y pe 1 Err or  
P o w er  
Detect a ble 
differe nce i n 
pr o p orti o ns 
c o m p are d t o 5 0 %  
EI A  
9 0 ( 4 5)  
0. 0 5  
0. 8  
0. 7 7 2 5  
EI A  
9 0  ( 4 5) 
0. 1  
0. 8  
0. 7 4 5 8  
EI A  
9 0  ( 4 5) 
0. 2  
0. 8  
0. 7 1 3 3  
N A A T  
1 8 0  ( 9 0) 
0. 0 5  
0. 8  
0. 7 0 0 3  
N A A T  
1 8 0  ( 9 0) 
0. 1  
0. 8  
0. 6 7 9 3  
N A A T  
1 8 0  ( 9 0) 
0. 2  
0. 8  
0. 6 5 4 3  
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 0  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
F or p has e II st u dies it is t y pical t o acce pt a t y pe 1 err or of greater t ha n 0. 0 5 ( Sc h oe nfel d 1 9 8 0; 
K ha n 2 0 1 2). F or t his p hase II st u d y, we will acce pt a differe nce b et wee n i nter ve nti o n gr o u ps t hat 
meets a t y p e I err or t hres h ol d of 0. 2. T heref ore, w e will ha ve 8 0 % p o w er t o detect a  differe nce of 
0. 2 1 3 3 ( 5 0 % t o 7 1. 3 3 %) i n t he EI A gr o u p, a n d a differe n ce of 1 5. 4 3 % ( 5 0 % t o 6 5. 4 3 %) i n t he 
N A A T gr o u p.   T h e p o wer calc ulati o ns w ere p erf or me d usi n g P A S S 1 6 (P o wer A n al ysis a n d 
Sa m ple Size S oft ware ( 2 0 1 8). N C S S, L L C. Ka ys ville, Uta h, U S A, ncss.c o m/s oft ware/ pass. ). 
8. 4. 
St atistic al Met h o ds  
8. 4. 1.  B aseli ne D at a 
Baseli ne a n d de m o gr a p hic c har acteristics, as well as vital si g ns , la b orat or y val ues, a n d ra di ol o gic 
st u d y res ults, will be s u m marize d b y sta n d ar d des cri pti ve statistics (i ncl u di n g mea n a n d sta n dar d 
de viati o n f or c o nti n u o us varia bles s uc h as a ge a n d sta n d ar d perce nta ges f or cate g orical varia bl es 
s uc h as ge n der). C ollecte d varia bles will i ncl u de b ut n ot be li mite d t o: b o d y mass i n de x ( B MI), 
c o m or bi d me dical c o n diti o ns, use of i m m u n os u p pressi ve me dicati o ns, use of pr ot o n p u m p 
i n hi bit or ( P PI) or H 2 a nta g o nist me dicati o ns, use of c o nc urre nt n o n- C DI directe d a nti bi otics, 
h os pital le n gt h of sta y a n d le vel of care. Ti me b et wee n C DI dia g n osis a n d i nter ve nti o n will als o 
be assesse d .  
8. 4. 2.  Effic ac y A n al ysis  
A n i nte nti o n t o treat a nal ysis will be perf or me d f or t he pri mar y  o utc o me of cli nical res ol uti o n of 
diarr hea wit h o ut rec urre n ce i n s u bjects wit h R -C DI at 8 wee ks f oll o wi n g F M T. A l o gistic 
re gressi o n m o del will be use d t o c o m pare t h e t w o st u d y gr o u ps (si n gle- d os e vers us d o u ble- d os e) 
t o detect s u peri orit y of a d ose. A p-val ue ( o ne -si d e d) of < 0. 2 will be c o nsi dere d si g nifica nt. As 
a b o ve, t he pri mar y a nal ysis will be stratifie d base d o n t he m ost rece nt p ositi ve C DI test ( N A A T 
vers us EI A) pri or t o e nr oll me nt . Per pr ot oc ol a nal ysis will als o be perf or m e d, base d o n recei ve d 
(rat her t h a n ra n d o mize d) treat me nt. 
8. 4. 3.  I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d.  
8. 4. 4.  S af et y A n al ysis  
All s u bjects e ntere d i nt o t he st u d y a n d ra n d o mize d will ha ve detaile d i nf or mati o n c ollecte d o n 
a d verse e ve nts starti n g at e nr oll me nt a n d f or t he d urati o n of f oll o w- u p, as d escri be d else w here. 
T he pri mar y safet y e n d p oi nts of fre q ue n c y of A Es, S A Es, a n d A E SIs will be descri b e d.  
8. 4. 5.   E x pl or at or y A n al yses 
T o c har acterize ( 1) t he b acterial c o m m u nit y c o m p ositi o n of t he a d mi nistere d P M T pr o d uct, we 
will a p p l y 1 6 S ri b os o mal R N A (r R N A) ge ne se q u e nci n g t o t he dr u g s u bsta nce. T o c h aracterize 
( 2) t he h ost i m m u ne p he n ot y pe ass ociate d wit h R- C DI, we will perf or m L u mi ne x bea d assa y 
(c yt o ki n e/c he m o ki ne le v els) a n d fl o w c yt o metric a nal ysis ( gra n ul oc yt e/ m o n o n uclear cell c o u nts) 
t o ser u m a n d bl o o d s peci me ns c ollecte d as p art of r o uti ne cli nical care pri or t o F M T.  
 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 1  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
8. 5. 
S u bject P o p ul ati o n(s) f or A n alysis  
F or t he pri mar y a nal ysis, a n i nte nti o n-t o-treat (I T T) p o p ulati o n Sec o n dar y per -pr ot oc ol a nal yses 
will als o be perf or m e d. All ra n d o mize d s u bjects will be i ncl u de d i n t he latter a nal yses.  
9.  S af et y a n d A d verse E ve nts  
9. 1. 
Defi niti o ns  
9. 1. 1.  A d verse E ve nt  
A n a d vers e e ve nt ( A E) is a n y u nt o w ar d me dical o cc urre nce ass ociat e d wit h t he use of a dr u g i n 
h u ma ns, w het her or n ot c o nsi dere d dr u g relate d. I nterc urre nt ill nesses or i nj uries s h o ul d be 
re gar d e d as a d v erse e ve nts.   
 
A pre - e xisti n g c o n diti o n s h o ul d be rec or de d as a n a d verse e ve nt if t he fre q u e nc y, i nte nsit y or t he 
c haracter of t he c o n diti o n c ha n ges.  
9. 1. 2.  Seri o us A d verse E ve nt  
A d verse e ve nts ar e classifie d as seri o us or n o n -seri o us.  A seri o us a d vers e e ve nt ( S A E) is a n y 
A E t hat, i n t he vie w of eit her t he i n vesti gat or or t h e s p o ns or, is:  
•  fatal 
•  life-t hreat e ni n g 
•  re q uires or pr ol o n gs h os pital sta y 
•  res ults i n persiste nt or si g nifica nt disa bilit y or i nca pacit y 
•  a c o n ge nital a n o m al y or birt h defect  
•  a n i m p orta nt me dical e v e nt  
 
I m p ort a nt me dical e v e nts are t h ose t hat ma y n ot b e i m me diatel y life t hreat e ni n g, b ut are cl earl y 
of maj or cli nical si g nifica nce.  T h e y ma y je o par di ze t he s u bject, a n d ma y re q uire i nter v e nti o n t o 
pre ve nt o ne of t he ot her s eri o us o utc o mes n ote d a b o ve.  F or e x a m ple, dr u g o ver d ose or a b use, a 
seiz ure t hat di d n ot res ult i n i n- patie nt h os pitalizati o n, or i nte nsi ve treat me nt of br o nc h os pas m i n 
a n e mer ge nc y de p art me nt w o ul d t y picall y be c o nsi dere d seri o us. 
9. 1. 3.  A d verse E ve nts of S peci al I nterest ( A E SI)  
Base d o n pri or p u blis he d e x perie nce wit h F M T- ass ociate d ris ks ( Ta bl e 1 ), we ha ve d efi ne d 
se veral a d vers e e ve nts of s pecial i nterest.  
 
I n t he i nitial, 6 0- mi n ute be dsi de o bser v ati o n peri o d f oll o wi n g a d mi nistrati o n of i n vesti gati o nal 
pr o d uct, s u bjects will be m o nit ore d wit h cl ose atte nti o n t o t he f oll o wi n g:  
•  aller gic r eacti o n (te m p er at ure, s ki n ras h, h eart rat e, or bl o o d press ure c h a n ge as alrea d y 
descri be d)  -- P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  se psis or s h oc k (te m perat ure, heart rate, or bl o o d press ure c ha n ge as alrea d y descri be d) 
– P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  b o wel i nj ur y (a b d o mi nal pai n c ha n ge as alrea d y d escri be d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 2  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
•  as pirati o n (res pir at or y r ate or o x y ge n sat urati o n c h a n ge as alrea d y d escri b e d)  – P M T -
0 0 2 a n d 0 0 3 o nl y 
 
I n t he s u bs e q ue nt, 7- d a y m o nit ori n g peri o d f oll o wi n g a d mi nistrati o n of i n v esti gati o nal pr o d u ct, 
s u bjects will be m o nit ore d wit h cl ose atte nti o n t o t he f oll o wi n g: 
•  d o n or- deri ve d i nfecti o n (te m perat ure or a b d o mi nal pai n c ha n ge as alrea d y descri be d)  – 
P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  w orse ni n g C DI (te m p erat ure,  c ha n ge i n st o ol fre q u e nc y/ q ua ntit y or a b d o mi nal pai n, or 
e mesis as alrea d y descri b e d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 
 
I n t he s u bs e q ue nt, 3 0-, 5 6 -, 9 0-, a n d 1 8 0- d a y m o nit ori n g peri o ds, s u bjects will be m o nit ore d wit h 
cl ose atte nti o n t o t he f oll o wi n g:  
•  tra ns mitte d i nfecti o n (te m perat ure or a b d o mi nal pai n c ha n ge as alrea d y d escri be d) – 
P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  rec urre nt C DI (t e m perat ure, c ha n ge i n st o ol fre q u e nc y/ q u a ntit y or a b d o mi nal pai n, or 
e mesis as alrea d y descri b e d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  meta b olic c ha n ges ( p ol y d i psia, p ol y uria, w ei g ht gai n or wei g ht l oss) – P M T - 0 0 1, 0 0 2, 
a n d 0 0 3 
9. 1. 4.  E x pecte d A d verse E ve nts  
Base d o n o ur o w n e x peri e nce a n d t he p u blis he d literat ure ( Ta bl e 1 ), we e x pect t hat 
gastr oi ntesti nal s y m pt o ms (i ncl u di n g fe ver, as pirati o n, belc hi n g, bl oati n g, n a usea or v o miti n g, 
gastr o es o p ha geal refl u x, a b d o mi nal cra m ps, a b d o mi nal pai n, diarr hea, c o nsti pati o n) ma y be 
co m m o n p ost a d mi nistrati o n of all t hree  i n vesti gati o nal pr o d ucts, b ot h as a c o nse q ue nce of t he 
u n derl yi n g disease bei n g tr eate d, a n d p ot e ntiall y as a n a d vers e effect of t he a d mi nistere d 
pr o d uct. 
 
T o disti n g uis h a ca us al relati o ns hi p bet wee n t hese A Es a n d t he i n vesti gati o nal pr o d uct, we will 
set a t hres h ol d of > = 5 0 % i ncrease i n gastr oi ntesti nal s y m pt o m se v erit y  (e. g., n u m ber of st o ols or 
v ol u me of diarr hea; n u m ber of v o miti n g e pis o des or h o urs/ da y of na us ea) as c o m pare d t o 
s y m pt o m se verit y i n t he 4 8- h o ur peri o d s urr o u n di n g t he i nter v e nti o n. 
9. 2. 
Rec or di n g of A dverse E ve nts  
Safet y will be assesse d b y m o nit ori n g a n d rec or di n g p ote ntial a d v erse effects usi n g t he C o m m o n 
T o xicit y Criteria v ersi o n 5. 0 ( C T C A E V 5. 0) at eac h st u d y visit. Partici pa nts will be m o nit ore d 
b y me dical hist ories, p h ysical e x a mi nati o ns, a n d ot her st u dies.  If C T C A E V 5. 0  gra di n g d oes n ot 
e xist f or a n a d verse e ve nt, t he se verit y of mil d, m o derate, s e vere, life-t hreat e ni n g, a n d deat h, 
c orres p o n di n g t o Gr a des 1- 5, will be use d w he n e v er p ossi ble. 
 
At eac h c o ntact wit h t he s u bject, t he i n vesti gat or will see k i nf or mati o n o n a d verse e ve nts b y n o n-
directi ve q uesti o ni n g a n d, as a p pr o priat e, b y e x a mi nati o n. A d verse e v e nts ma y als o be detecte d 
w he n t he y ar e v ol u nteere d b y t he s u bject d uri n g t he scree ni n g pr ocess or bet wee n visits, or 
t hr o u g h p h ysical e x a mi nati o n, la b orat or y test, or ot her assess me nts. I nf or mati o n o n all a d verse 
e ve nts will be rec or de d i n t he s o urce d o c u me ntati o n. T o t he e xte nt p ossi ble, a d vers e e v e nts will 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 3  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
be rec or de d as a dia g n osis a n d s y m pt o ms use d t o ma ke t he dia g n osis rec or de d wit hi n t he 
dia g n osis e v e nt.   
 
As m uc h as p ossi ble, eac h a d verse e ve nt or f oll o w- u p i nf or mati o n will be e val uate d t o 
deter mi ne:  
1.  Se verit y gra de ( C T C A E V 5. 0  Gra d e 1 - 5)  
2.  D urati o n (start a n d e n d d ates) 
3.  Relati o ns hi p t o t he st u d y treat me nt or pr o cess – [ Reas o na ble p ossi bilit y t hat A E is 
relate d: N o ( u nrelate d/ n ot s us pecte d) or Y es (a s us pecte d a d v erse reacti o n)].  If yes 
(s us pecte d) - is t he e ve nt p ossi bl y, pr o ba bl y or d efi nitel y relat e d t o t he i n vesti gati o nal 
treat me nt?  
4.  Acti o n ta ke n wit h res p ect t o st u d y or i n vesti gati o nal treat me nt or pr o cess ( n o ne, d ose 
a dj uste d, te m p oraril y i nterr u pte d, p er ma ne ntl y disc o nti n ue d, u n k n o w n, n ot 
a p plica ble)  
5.  W het her me dicati o n or t hera p y ta k e n ( n o c o n c o mita nt me dicati o n/ n o n- dr u g t hera p y, 
c o nc o mita nt me dicati o n/ n o n- dr u g t hera p y)  
6.  W het her t he e ve nt is seri o us 
 
O nce a n a d vers e e v e nt is detecte d, it s h o ul d be f oll o we d u ntil its res ol uti o n or u ntil it is j u d ge d t o 
be per ma n e nt, a n d assess me nt s h o ul d be ma de at eac h visit ( or m ore fre q u e ntl y, if necessar y) of 
a n y c ha n ges i n se verit y, t he s us pecte d relati o ns hi p t o t h e st u d y treat me nt, t he i nter ve nti o ns 
re q uire d t o treat it, a n d t he o utc o me.   
9. 3. 
Re p orti n g of A dverse Eve nts  a n d U n a ntici p ate d Pr o ble ms 
 
Re p orti n g peri o d  
A d verse e ve nts will be re p orte d fr o m t he ti me of i nf or me d c o ns e nt u ntil st u d y c o m pleti o n.  
 
I n vesti g at or re p orti n g: n otif yi n g t he st u d y s p o ns or  
T he s p o ns or m ust be n otifie d wit h i n 2 4 h o urs of lear ni n g of a n S A E o cc urre nce, re gar dless of 
s us pecte d ca usalit y (e. g., relati o ns hi p t o st u d y dr u g(s) or st u d y pr oce d ure or disease pr o gressi o n).   
 
At t he ti me of t he i nitial n otificati o n, t he f oll o wi n g i nf or m ati o n s h o ul d be pr o vi de d: 
•  St u d y i d e ntifier  
•  S u bject n u m ber 
•  A descri pti o n of t he e v e nt 
•  Date of o nset  
•  C urre nt stat us 
•  W het her st u d y treat me nt was 
disc o nti n ue d 
•  T he reas o n t he e ve nt is cl assifie d as 
seri o us 
•  I n v esti gat or assess me nt of t he 
ass ociati o n bet wee n t he e ve nt a n d 
st u d y treat me nt 
 
F oll o w- u p i nf or mati o n o n S A Es s h o ul d be re p orte d w he n u p dates are a vail a ble, as a f oll o w- u p t o 
t he i nitial S A E re p ort, a n d s h o ul d i ncl u de b ot h t he f oll o w- u p n u m ber a n d re p ort date.  Ne w 
i nf or mati o n o n o n g oi n g s eri o us a d vers e e v e nts s h o ul d be pr o vi de d pr o m ptl y t o t he s p o ns or. T he 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 4  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
f oll o w- u p i nf or mati o n s h o ul d descri be w h et her t h e e ve nt has res ol ve d or c o nti n ues, if t here are 
a n y c ha n ges i n assess me nt, if a n d h o w it was treat e d, a n d w het h er t he patie nt c o nti n ue d or 
wit h dre w fr o m st u d y partici pati o n.  T he i n vesti gat or m ust f oll o w t he e ve nt t o res ol uti o n or u ntil 
t he e ve nt is dee me d a n d d oc u me nte d irre versi ble, w hic he ver is l o n ger.  
 
Rec urre nt e pis o des, c o m plicati o ns, or pr o gressi o n of t he i nit ial S A E m ust be re p ort e d as t he 
f oll o w- u p t o t he ori gi n al e pis o de wit hi n 2 4 h o urs of t he i n vesti gat or recei vi n g t he f oll o w- u p 
i nf or mati o n. A n S A E c o nsi dere d c o m pletel y u nrelate d t o a pre vi o usl y re p orte d o ne s h o ul d be 
re p orte d se p ar atel y as a n e w e ve nt.  
 
In a d diti o n, all u ne x pecte d fatal or life -t hreat e ni n g s us pecte d a d v erse reacti o n will be re p orte d t o 
t he F D A as s o o n as p ossi ble b ut i n n o case later t ha n 7 cale n d ar da ys after t he s p o ns or’s i nitial 
recei pt of t h e i nf or mati o n.  Ot her S A Es t hat are b ot h, u ne x pecte d a n d relat e d t o t he st u d y dr u g 
( S U S A R) will be re p orte d t o t he F D A as s o o n as p ossi ble b ut n o later t ha n 1 5 cale n dar da ys after 
t he s p o ns or k n o wle d ge of t he e ve nt. 
 
 
I n vesti g at or Re p orti n g: L oc al Re p orti n g Re q uire me nts  
T he i n vesti gat or will re p ort A Es a n d S A Es t o his/ her I R B/ E C of rec or d a n d ot her l ocal 
re g ulat or y gr o u ps p er t he l ocal re q uir e me nts.  
9. 3. 1.  Pre g n a nc y  
Pre g n a nc y, i n a n d of itself, is n ot re gar d e d as a n A E u nless t here is s us pici o n t hat st u d y dr u g or 
pr ocess ma y h a ve i nterf ere d wit h t he effecti ve n ess of a c o ntrace pti ve me di cati o n or met h o d. 
W he n a pre g na n c y has b ee n c o nfir me d i n a s u bject d uri n g mat er nal or p at er nal e x p os ure t o st u d y 
dr u g a n d/ or pr o cess, t he f oll o wi n g pr oce d ures s h o ul d be f oll o we d t o e ns ure s u bject safet y: 
 
Data o n fet al o utc o me ar e c ollecte d f or re g ulat or y re p orti n g a n d dr u g s afet y e v al uati o n. F oll o w-
u p s h o ul d be c o n d ucte d f or eac h pre g n a nc y t o det er mi ne o utc o me, i ncl u di n g s p o nta n e o us or 
v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese nce or a bs e nce of a n y birt h defects, 
c o n ge nital a b n or malities, or mater nal a n d/ or ne w b or n c o m plicati o ns. A cas e re p ort f or m will 
ca pt ure t hes e o utc o mes f or pre g na nt s u bjects, a n d t he s p o ns or will be n otifie d wit hi n 2 4 h o urs of 
rec or d e d a n a d vers e e ve nt relate d t o pre g n a nc y. 
9. 4.  
 T o xicity M a n a ge m e nt, St o p pi n g R ules a n d St u dy Ter mi n ati o n   
E nr oll me nt a n d a d mi nistrati o n of t he st u d y pr o d u ct will be halte d pe n di n g re vie w b y t he st u d y 
staff a n d D ata Saf et y M o nit ori n g B o ar d  ( D S M B) if a n y s u bject e x perie n ces an A E t hat is  
assesse d as ( 1) seri o us (i. e., t hat res ults i n si g nifica nt s y m pt o ms pre ve nti n g n or mal dail y 
acti vities or re q uiri n g  h os pitalizati o n ), ( 2) u ne x pecte d  treat me nt e mer ge nt, a n d ( 3) relate d t o 
a d mi nistrati o n of t he st u d y pr o d u ct. E nr oll me nt a n d a d mi nistrati o n of t he st u d y pr o d u ct will be 
halte d pe n di n g re vie w b y t he st u d y staff a n d D ata Safet y M o nit ori n g B oar d ( D S M B) if a n y 
s u bject e x perie nces a s us pected or pr o ve n i nfecti o n assesse d as relate d t o t he st u d y pr o d u ct. T he 
re vie w of t h ese a d v erse e ve nts, a n d a n y decisi o n t o pre mat urel y st o p s u bject e nr oll me nt, will be 
deter mi ne d b y t he Me di cal Direct or a n d D S M B.   

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 5  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
9. 5. 
Me dic al M o nit ori n g  
It is t he r es p o nsi bilit y of t he Pri nci pal I n vesti gat or t o o versee t he s afet y of t he st u d y at his/ her 
site.  T his safet y m o nit ori n g will i ncl u de caref ul assess me nt a n d a p pr o pri ate re p orti n g of a d vers e 
e ve nts as n ote d a b o v e.   
9. 5. 1.  D at a a n d S af et y M o nit ori n g Pl a n 
A Dr u g Safet y M o nit ori n g Pla n has b ee n de v el o pe d base d o n ris k a n d is des cri be d i n a se p arat e 
d oc u me nt.  T he m o nit ori n g pla n will  i ncl u de the f oll o wi n g  c o m p o ne nts: 
 
•  Pri nci pal I n v esti gat or m o nit ori n g  
•  T he S p o ns or Me dical Dir ect or 
•  Data Safet y a n d M o nit ori n g B oar d ( D S M B)   
9. 5. 2.  D at a S af et y M o nit ori n g B o ar d  
A n i n de pe n de nt D S M B will perf or m e val u ati o ns of safet y dat a at s pecifie d i nter vals t hr o u g h o ut 
t he st u d y a n d ma k e r ec o m me n dati o ns t o t he S p o ns or re gar di n g f urt her c o n d uct of t he st u d y. T h e 
D S M B will e val uate s u bj ect saf et y as s pecifi e d i n t he D S M B C harter.  
1 0.  S t u d y A d mi nistr ati o n, D at a H a n dli n g a n d Rec or d Kee pi n g 
1 0. 1.  C o nfi de nti ality  
I nf or mati o n a b o ut st u d y s u bjects will be ke pt c o nfi de ntial a n d ma na ge d acc or di n g t o t he 
re q uire me nts of t h e Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 ( HI P A A).  
T h ose re g ulati o ns re q uire a si g ne d s u bj ect a ut h orizati o n i nf or mi n g t he s u bject of t he f ol l o wi n g:  
•  W hat pr otecte d healt h i nf or mati o n ( P HI) will be c ollecte d fr o m s u bjects i n t his st u d y  
•  W h o will ha ve access t o t hat i nf or mati o n a n d w h y 
•  W h o will use or discl ose t hat i nf or mati o n  
•  T he ri g hts of a r esearc h s u bject t o re v o ke t heir a ut h orizati o n f or use of t heir P HI.  
 
I n t he e ve nt t hat a s u bj ect re v o kes a ut h orizati o n t o c ollect or use P HI, t he i n vesti gat or, b y 
re g ulati o n, retai ns t he a bilit y t o use all i nf or mati o n c ollecte d pri or t o t he re v ocati o n of s u bject 
a ut h orizati o n.  F or s u bjects t hat ha ve re v o k e d a ut h orizati o n t o c ollect or use P HI, atte m pts 
s h o ul d be ma de t o o btai n per missi o n t o c ollect at least vital stat us (i.e. t hat t he s u bject is ali ve) at 
t he e nd of t heir sc h e d ule d st u d y peri o d. 
1 0. 2.  F ut ure Use of St ore d S peci m e ns a n d D at a  
St o ol a n d bl o o d  s peci me ns c ollecte d as a b o ve (Secti o n 7. 6 ) ma y be preser v e d i n fr oze n st ora ge f or 
f ut ure a n al ys es. T he d ata ge n erat e d fr o m t h ose s p eci me ns will o nl y be use d f or res earc h p ur p os es. 
It will n ot be s har e d wit h s u bjects or be use d t o direct treat me nt.  
1 0. 3.  D at a C ollecti o n a n d M a n a ge m e nt  
Case Re p ort F or ms ( C R Fs) will be c o m plete d, wit h  c o pies eit her pri nte d a n d st ore d i n bi n ders i n 
a sec ur e l ocati o n or s ec ur el y st or e d i n a n a p pr o v e d electr o nic s yste m t o w hi c h o nl y st u d y 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 6  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
pers o n nel will ha ve acc ess. S u bject diaries will als o be c ollecte d a n d st ore d i n a sec ure l ocati o n. 
S u bjects will be assi g ne d a u ni q ue st u d y i de ntifi cati o n n u m ber , a n d P HI will be ke pt se paratel y 
wit h a master file st ore d o n a sec ur e, pass w or d - pr otecte d c o m p uter. Li n k a ge t o P HI will be 
st ore d u ntil st u d y a nal ysis a n d p u blicati o n c o m pleti o n, a n d t he n will be destr o ye d.  
 
E x pl orat or y micr o bi o me a nal ysis will be p erf or m e d  o n st o ol s peci me ns a n d e x pl orat or y i m m u ne 
res p o nse p he n ot y pi n g usi n g fl o w c yt o metr y will be  perf or me d usi n g a u ni q ue st u d y 
i de ntificati o n n u m ber, wit h n o ass ociate d P HI. T h e e x pl orat or y a nal ysis of s u bject micr o bi o me 
c o m p ositi o n ( will or will n ot) be s hare d wit h t he s u bjects treati n g p h ysicia n.  
 
St o ol a n d bl o o d s peci me ns will be c o de d t o mai ntai n patie nt c o nfi de ntialit y a n d will be st ore d 
acc or di n g t o r e g ulati o ns. T he s u bject s pecific st o ol sa m ples be trac k e d wit h a master file li n ki n g 
P HI t o st u d y I D n u m bers, w hic h will be ke pt o n a sec ure, p ass w or d- pr otect e d c o m p uter.  
1 0. 4.  R ec or ds Rete nti o n  
Data (el ectr o nic  a n d pa p er) will be st ore d i n a sec ure l ocati o n u ntil st u d y a nal ysis a n d 
p u blicati o n c o m pleti o n, after w hic h a n y li n ka ge t o P HI will be  d estr o ye d. A n o n y mize d micr o bial 
n ucleic aci d se q ue nce dat a a n d ass oci ate d meta d ata will be u pl oa de d o n p u blic data bases (i. e., 
t he Nati o nal Ce nter f or Bi otec h n ol o g y I nf or mati o n’s Se q ue nce R ea d Arc hi ve) as re q uire d b y 
f u n di n g a ge ncies. 
1 1.  St u d y M o nit ori n g, A u diti n g, a n d I ns pecti n g  
1 1. 1.  St u dy M o nit ori n g Pl a n  
T his st u d y will be m o nit ore d acc or di n g t o t he dat a safet y m o nit ori n g pla n. T he i n vesti gat or will 
all ocate a d e q uate ti me f or s uc h m o nit ori n g acti vities.  T he I n vesti gat or will als o e ns ure t hat t he 
m o nit or or ot her c o m plia nce or q ualit y ass ura nce re vie wer is gi ve n access t o all t he a b o ve n ote d 
st u d y-r elate d d oc u m e nts a n d st u d y r elate d facilities (e. g. p har mac y, dia g n ostic la b orat or y, etc.), 
a n d has a de q u ate s pace t o c o n d uct t he m o nit ori n g visit. 
1 1. 2.  D at a Q u ality Ass ur a nce  
D uri n g  m o nit ori n g visits,   t he m o nit or will  re vie w C R Fs  t o  e ns ure data acc urac y, 
c o m plete ness, a n d clarit y, i ncl u di n g la b orat or y re p orts a n d ot her s u bject rec or ds wit h t he 
sti p ulati o n t hat s u bject c o nfi de ntialit y will be stri ctl y mai ntai ne d i n acc or d a nce wit h l ocal a n d 
fe der al re g ulati o ns, i ncl u di n g HI P A A re q uire me nts. I nsta n ces of missi n g or u ni nterr u pti ble data 
will be res ol ve d i n c o or di nati o n wit h t he I n vesti gat or. 
1 1. 3.  A u diti n g a n d I ns pecti n g 
T he i n vesti gat or will per mit st u d y -relate d m o nit ori n g, a u dits, a n d i ns pecti o ns b y t he E C/I R B, t h e 
s p o ns or, g o v er n me nt r e g ulat or y b o dies, a n d U ni v ersit y c o m plia nce a n d q u alit y ass ura nce gr o u ps 
of all st u d y r elate d d oc u me nts (e. g. s o urce d oc u me nts, re g ulat or y d oc u m e nts, data c ollecti o n 
i nstr u me nts, st u d y d ata et c.).  T he i n vesti gat or s h all n otif y t he S p o ns or of all a u dits a n d 
i ns pecti o ns b y r e g ulat or y b o dies.  T he i n vesti gat or will e ns ure t he ca pa bilit y f or i ns pecti o ns of 
a p plica ble st u d y-r elate d f acilities (e. g. p har m ac y, dia g n ostic la b orat or y, et c.). Partici pati o n as a n 

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 7  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
i n vesti gat or i n t his st u d y i m plies acce pta n ce of p ot e ntial i ns pecti o n b y g o v er n me nt re g ulat or y 
a ut h orities a n d a p plica b l e U ni versit y c o m plia nce a n d q ualit y ass ura nce offices. 
1 2.  Et hic al C o nsi der ati o ns 
T his st u d y is t o be c o n d u cte d i n acc or da n ce wit h a p plica ble U S g o v er n me nt re g ulati o ns a n d 
i nter nati o nal sta n dar ds of G o o d Cli nical Practice, a n d a p plica ble i nstit uti o nal researc h p olicies 
a n d pr oce d ures.  
 
T his pr ot oc ol a n d a n y a m e n d me nts will be s u b mitte d t o a pr o perl y c o nstit ute d i n de pe n de nt 
Et hics C o m mittee ( E C) or I nstit uti o nal Re vie w B o ar d (I R B), i n a gree me nt wit h l ocal le gal 
prescri pti o ns, f or f or mal a p pr o val of t he st u d y c o n d uct.  T he decisi o n of t he E C/I R B c o ncer ni n g 
t he c o n d uct of t he st u d y will be ma de i n writi n g t o t he i n vesti gat or a n d a c o p y of t his decisi o n 
will be pr o vi de d t o t he s p o ns or bef or e c o m me nce me nt of t his st u d y.  
 
Pr ot oc ol m o dificati o ns, e x ce pt t h ose i nte n de d t o re d uce i m me diate ris k t o st u d y s u bjects, ma y b e 
ma de o nl y b y t h e U ni versit y of Pe n ns yl va nia a n d t he S p o ns or. A pr ot oc ol c ha n ge i nte n d e d t o 
eli mi nate a n a p pare nt i m me diate hazar d t o s u bjects ma y be i m ple me nt e d i m me diatel y, pr o vi d e d 
t he I R B/I E C is n otifie d wit hi n 5 da ys. 
A n y p er ma ne nt c ha n ge t o t he pr ot oc ol m ust be ha n dle d as a pr ot oc ol a me n d me nt. T he writte n 
a me n d me nt m ust be s u b mitte d t o t he I R B/I E C a n d t he i n vesti gat or m ust a wait a p pr o val bef ore 
i m ple me nti n g t he c ha n ges. T he S p o ns or will s u b mit pr ot oc ol a me n d me nts t o t he a p pr o priat e 
re g ulat or y a ut h orities f or a p pr o val. 
1 2. 1.  Ris ks 
T he mai n ris ks of t his st u d y are r elate d t o a d mi nistrati o n  of t he i n vesti gati o nal pr o d uct. T he m ost 
se vere p ossi ble ris ks i ncl u de: aller gic reacti o n,  d o n or-deri ve d i nfecti o n , as pirati o n (f or u p per 
gast r oi ntesti nal a d mi nistr ati o n), b o wel perf orati o n (f or l o wer gastr oi ntesti nal a d mi nistrati o n), 
a n d deat h. Ot her ris ks i ncl u de: na usea, v o miti n g, a b d o minal pai n, diarr h ea, flat ule nce, fe ver.  
Pr o d uct s pecific ris ks are descri be d i n Secti o n  9. 1. 4 . 
 
T he oretical  l o n g-t er m ris ks ma y i ncl u de: c ha n ges i n meta b olis m, wei g ht c h a n ges, de vel o p me nt 
of a ut oi m m u ne c o n diti o ns.  
 
Ot her ris ks i ncl u de l oss of pri vac y or c o nfi de ntialit y, as a res ult of st u d y staff i nteracti n g wit h 
s u bjects. 
 
T hese ris ks will be disc usse d wit h s u bjects d uri n g t he i nf or me d c o nse nt pr ocess. T he eli gi bilit y 
criteria will hel p miti gat e t hese ris ks (e. g., e x cl u di n g s u bjects wit h ne utr o p e nia or b o wel 
perf or ati o n, a n d n ot per mitti n g s u bjects at ris k f or as pirati o n t o recei ve i n vesti gati o nal pr o d uct 
via u p per gastr oi ntesti nal  deli ver y). T o mi ni mize t he ris k of pri vac y a n d c o nfi de ntialit y l oss, t he 
mi ni m u m n u m ber of re q uire d st u d y staff will i nteract wit h s u bjects, a n d all c ollecte d data will be 
pr otecte d as a b o ve.  

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 8  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1 2. 2.  Be nefits  
P ote ntial direct be nefits i ncl u de: c ure or i m pr o ve me nt of C DI s y m pt o ms m ore q uic kl y t h a n wit h 
sta n dar d of car e, re d u cti o n i n ris k of c o m plicati o ns of C DI ( deat h, nee d f or s ur ger y), re d ucti o n i n 
ris k of rec urre n ce of C DI, w hic h ha ve b ee n s u g geste d b y o bs er vati o nal st u dies t o date (Ta ble 1 ). 
I n dir ect be n efits i ncl u de c o ntri b uti n g t o me dical k n o wle d ge a b o ut t he utilit y of F M T i n t his 
st u d y p o p ulati o n a n d t her ef ore h el pi n g p atie nts w h o ha ve t his disease i n t he f ut ure. 
1 2. 3.  Ris k Be nefit Assess m e nt  
Base d o n t h e ris ks a n d be nefits o utli ne a b o ve, t he be nefits of t his st u d y o ut wei g h t h e p ote ntial 
ris ks. T his is a patie nt p o p ulati o n wit h si g nifica nt ill ness at hi g h ris k f or c o m plicati o ns, a n d t he 
i n vesti gati o nal pr o d u cts are li kel y t o re d u ce t his ris k. W hile t here are p ote ntial a d verse o utc o m es 
ass ociate d wit h t his pr o d uct, pri or st u dies h a ve d e m o nstrate d t hat t he ris k of t hese occ urri n g is 
relati vel y l o w.  
1 2. 4.  I nf or m e d C o nse nt Pr ocess / HI P A A A ut h oriz ati o n  
I nf or me d c o ns e nt m ust be o btai ne d bef ore a n y of t he baseli ne pr o ce d ures are perf or me d. T h e 
c o nse nt pr ocess will occ ur i n t he setti n g of t he p ote ntial s u bject’s re g ularl y sc he d ule d cli nical 
care or b y tele p h o n e after referral fr o m t he p ote nti al s u bject’s cli nical care t ea m. Writte n 
i nf or me d c o nse nt will be o btai ne d w he ne v er p ossi ble. I n cas es w here C O VI D- 1 9 is olati o n stat us 
or visit or p olicies precl u de a n i n- pers o n c o nse nt pr ocess, ver bal c o ns e nt will be o btai ne d 
utilizi n g a wit nesse d c o nse nt. T his will be t h e n d oc u me nte d i n b ot h t he electr o nic healt h rec or d 
a n d t he data c ollecti o n s yste m. A n e x pla nati o n of t he trial a n d disc ussi o n of t he p ossi ble ris ks 
a n d disc o mf orts will be gi ve n b y t he I n vesti gat ors a n d/ or st u d y staff. O nl y t h ose p ote ntial 
s u bjects w h o f ulfill all eli gi bilit y criteria will be e ntere d i nt o t he trial. I nf or me d c o nse nt will ta ke 
place as a n o n g oi n g di al o g ue b et wee n t he I n vesti gat or/st u d y staff a n d s u bjects d uri n g t he e ntire 
d urati o n of t heir partici pati o n. P ote ntial s u bjects t hat are u n a ble t o rea d t he st u d y c o nse nt a n d/ or 
d o n ot ha ve t he o p p ort u nit y t o ta ke h o me a n d re vi e w wit h fa mil y/frie n ds or d o n ot prese nt i n t he 
cli nic wit h a fa mil y m e m ber will ha ve t he c o nse nt rea d t o t he m b y a st u d y t ea m me m ber i n t he 
prese nce of a n o n- partial pers o n t hat will verif y t h e c o nse nt has b ee n rea d i n f ull t o t he patie nt. 
Pri vac y will be preser ve d b y mi ni mizi n g t he n u m ber of st u d y staff i n c o ntact wit h t he p ote ntial 
s u bject. C oerci o n will be a v oi de d b y clearl y stati n g t hat decli ni n g t o partici pate will n ot affect 
cli nical car e. T he i nf or me d c o nse nt a n d HI P A A a ut h orizati o n will be d oc u me nte d o n pa per, a n d 
c o m plete d pa per rec or ds will be sca n ne d f or di gital st ora ge o n sec ure u ni versit y ser v ers. 
1 3.  St u d y Fi n a nces  
1 3. 1.  F u n di n g S o urce  
Pr o gr a m s u p p ort fr o m Pe n n Me dici ne, De p art me nt of Me dici ne, a n d Ce nt ers f or Diseas e C o ntr ol 
a n d Pre ve nti o n ( C D C) U 5 4 C K 0 0 0 4 8 5.   
1 3. 2.  C o nflict of I nterest  
All U ni versit y of Pe n ns yl va nia I n vesti gat ors will f oll o w t he U ni versit y of Pe n ns yl va nia P olic y 
o n C o nflicts of I nterest R elate d t o Researc h .  

 
P M T f or Rec urre nt-C DI  
 
P a ge 3 9  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1 3. 3.  S u bject Sti pe n ds or P ay m e nts 
T here are n o s u bject pa y me nts or sti pe n ds. 
1 4.  P u blic ati o n Pl a n  
T he i n vesti gat or is res p o nsi ble f or a ut h ori n g a fi n al cli nical st u d y re p ort a n d s hari n g wit h  t he 
s p o ns or tea m. T he Cli nical St u d y Re p ort will be iss ue d wit hi n 1 2 m o nt h s of data l oc k a n d t he 
res ults s u m mar y will be p oste d t o cli nicaltrials. g o v. as re q uire d b y le gal a gree me nt, l ocal la w, or 
re g ulati o n. A ma n uscri pt will be pr o gresse d f or p u blicati o n i n t he scie ntific literat ure if t he 
res ults pr o vi de i m p orta nt scie ntific or me dical k n o wle d ge. T his st u d y will be p u blis he d b y t he 
pri nci pal i n vesti gat or, Dr. La ut e n bac h. 
1 5.  Ref ere nces  
 
A gra w al M, Ar o nia dis O C, Bra n dt LJ, K ell y C, Free ma n S, S ura wicz C, Br o ussar d E, St oll ma n 
N, Gi o va nelli A, S mit h B, Ye n E, Tri ve di A, H u b ble L, K a o D, B or o d y T, Fi nla ys o n S, Ra y A, 
S mit h R. T he L o n g- ter m Efficac y a n d Safet y of Fecal Micr o bi ota Tra ns pla nt f or Rec urre nt, 
Se vere, a n d C o m plicat e d Cl ostri di u m difficile I nfecti o n i n 1 4 6 El derl y I n di vi d uals. J Cli n 
Gastr oe nter ol. 2 0 1 6 M a y; 5 0( 5): 4 0 3 – 4 0 7. P MI D: 2 6 3 5 2 1 0 6 
 
Ar o nia dis O C, Br a n dt LJ, Gree n b er g A, B or o d y T, Kell y C R, Mell o w M, S ura wicz C, Ca gle L, 
Nes hatia n L, St oll ma n N, Gi o va nelli A, Ra y A, S mit h R. L o n g- t er m F oll o w- u p St u d y of Fecal 
Micr o bi ota Tra ns pla n tati o n f or Se ver e a n d/ or C o m plicate d Cl ostri di u m difficile I nfecti o n: A 
M ultice nter E x perie nce. J Cli n Gastr oe nter ol. 2 0 1 6 Ma y; 5 0( 5): 3 9 8 – 4 0 2. P MI D: 2 6 1 2 5 4 6 0 
 
B oja n o va D P, B or d e nstei n S R. Fecal Tra ns pla nts: W hat Is Bei n g Tra nsferre d? P L o S Bi ol. 2 0 1 6 
J ul; 1 4( 7):e 1 0 0 2 5 0 3. P M CI D: P M C 4 9 4 2 0 7 2 
 
Ca m mar ota G, Ia nir o G, Gas barri ni A. Fecal micr o bi ota tra ns pla ntati o n f or t he treat me nt of 
Cl ostri di u m difficile i nfecti o n: a s yste matic re vie w. J Cli n Gastr oe nter ol. 2 0 1 4 Se p; 4 8( 8): 6 9 3 –
7 0 2. P MI D: 2 4 4 4 0 9 3 4 
 
Ca m mar ota G, Ia ni r o G, Til g H, Rajilić-St oja n o vić M, K u m p P, Sat o kari R, S o k ol H, Ar k kila P, 
Pi nt us C, Hart A, Se gal J, Al oi M, Mas ucci L, M oli nar o A, Scal daferri F, G as barri ni G, L o p ez-
Sa nr o ma n A, Li n k A, de Gr o ot P, de V os W M, H ö ge n a uer C, M alfert hei n er P, Mattila E, 
Mil osa vlje vić T, Nie u w d or p M, Sa n g ui netti M, Si mre n M, Gas barri ni A, E ur o pea n F M T 
W or ki n g Gr o u p. E ur o p ea n c o nse ns us c o nfere n ce o n faecal micr o bi ota tra ns pla ntati o n i n cli nical 
practice. G ut. B MJ P u blis hi n g Gr o u p; 2 0 1 7 A pr; 6 6( 4): 5 6 9 – 5 8 0. P M CI D: P M C 5 5 2 9 9 7 2 
 
Fis c her M, Si pe B, C he n g Y- W, P hel ps E, R o gers N, Sa gi S, B o h m M, X u H, Kassa m Z. Fecal 
micr o bi ota tra ns pla nt i n se vere a n d se v ere -c o m plicate d Cl ostri di u m difficile: A pr o misi n g 
treat me nt a p pr o ac h. G ut Micr o bes. 2 0 1 7 Ma y 4; 8( 3): 2 8 9 – 3 0 2. P M CI D: P M C 5 4 7 9 3 9 3 
 
Fis c her M, Si pe B W, R o gers N A, C o o k G K, R o b b B W, V u p pala nc hi R, Re x D K. Faecal 
micr o bi ota tra ns pla ntati o n pl us selecte d use of v a nc o m yci n f or se v ere- c o m plicate d Cl ostri di u m 

 
P M T f or Rec urre nt-C DI  
 
P a ge 4 0  of 4 1  
 
 
P M T f or R ec urre nt -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
difficile i nfecti o n: descri pti o n of a pr ot oc ol wit h hi g h s uccess rat e. Ali me nt P har mac ol T her. 
2 0 1 5 A u g; 4 2( 4): 4 7 0 – 4 7 6. P MI D: 2 6 0 9 6 3 2 0 
 
Ha milt o n MJ, Wei n gar de n A R, Sa d o ws k y MJ, K h or uts A. Sta n dar dize d fr o ze n pre parati o n f or 
tra ns pla ntati o n of fecal micr o bi ota f or rec urre nt Cl ostri di u m difficile i nfecti o n. A m J 
Gastr oe nter ol. A merica n C olle ge  of Gastr oe nt er ol o g y; 2 0 1 2 Ma y; 1 0 7( 5): 7 6 1 – 7 6 7. P MI D: 
2 2 2 9 0 4 0 5 
 
Ka o D, R oac h B, Sil va M, Bec k P, Ri o u x K, Ka pla n G G, C ha n g H-J, C o war d S, G o o d ma n KJ, 
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