Clinical trial NCT03973697
Conditions: Recurrent Clostridium Difficile Infection
Sponsor: University of Pennsylvania
Start date: 2020-01-13; Completion date: 2021-12-31
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, open label, comparative, Phase II study to determine which dose of fecal microbiota transplant using Penn Microbiome Therapy (PMT) products is most effective in treating and preventing recurrence of Clostridium difficile infection (C diff).

Detailed description:

Arms: arm 1: None arm 2: Administered within 24 hours
Interventions: intervention 1: Penn Microbiome Therapy - 001 intervention 2: Penn Microbiome Therapy - 002 intervention 3: Penn Microbiome Therapy - 003
Intervention descriptions: intervention 1: Fecal Microbiota for Transplant, enema product intervention 2: Fecal Microbiota for Transplant, suspension product intervention 3: Fecal Microbiota for Transplant, capsule product

Protocol documents:
Prot_SAP_000.pdf: 


 
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  
 
 
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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  
 
 
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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  
 
 
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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  
 
 
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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 
 
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2 2 2 9 0 4 0 5 
 
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K ha n I, Sar k er S -J, Hac ks ha w A. S maller sa m ple sizes f or p hase II tri als base d o n e x act tests 
wit h act ual err or r ates b y tra di n g - off t heir n o mi nal le vels of si g nifi ca nce a n d p o wer. Br J Ca ncer. 
2 0 1 2 N o v 2 0; 1 0 7( 1 1): 1 8 0 1 – 1 8 0 9. P M CI D: P M C 3 5 0 4 9 4 1 
 
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Lee YJ, Ar g uell o E P, J e n q R R, Litt ma n n E, Ki m GJ, Miller L C, Li n g L, Fi g uer oa C, R o bil otti E, 
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t he-I ntesti nal- Micr o bi o m e P MI D: 2 8 3 2 9 0 3 0 
 
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P M T f or Rec urre nt-C DI  
 
P a ge 4 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  
 
 
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P M CI D: P M C 4 0 6 8 2 5 7 
 
va n N o o d E, Vrieze A, Nie u w d or p M, F u e ntes S, Z oet e n dal E G, d e V os W M, Visser C E, 
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3 1; 3 6 8( 5): 4 0 7 – 4 1 5. P MI D: 2 3 3 2 3 8 6 7 
 
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2 0 1 3 Se p; 4 7( 8): 7 3 5 – 7 3 7. P M CI D: P M C 3 7 3 5 6 2 1 
 
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Y o u n gster I, Sa u k J, Pi n dar C, Wils o n R G, Ka pla n J L, S mit h M B, Al m EJ, Ge vers D, R ussell 
G H, H o h ma n n E L. Fecal micr o bi ota tra ns pla nt f or rela psi n g Cl ostri di u m difficile i nfecti o n usi n g 
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I nfect Dis. 2 0 1 4 J u n; 5 8( 1 1): 1 5 1 5 – 1 5 2 2. P M CI D: P M C 4 0 1 7 8 9 3 
 
Y o u n gster I, R ussell G H, Pi n dar C, Zi v- Bara n T, Sa u k J, H o h ma n n E L. Oral, ca ps ulize d, fr oze n 
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5; 3 1 2( 1 7): 1 7 7 2 – 1 7 7 8. P MI D: 2 5 3 2 2 3 5 9