Conditions: Clostridioides Difficile Infection
Keywords: Clostridioides difficile infection (CDI) ridinilazole Adolescents vancomycin C. Diff Clostridium difficile Diarrhea Infection Pediatric
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 2
Healthy volunteers: no

Brief summary:
Study to evaluate the safety of ridinilazole in adolescent subjects and how ridinilazole is metabolized.

Detailed description:

Arms:
arm 1: Ridinilazole dosed BID and a comparator placebo dosed QID, to maintain blind, for 40 doses over 10 days. arm 2: Vancomycin dosed QID and a Ridinilazole placebo dosed BID, to maintain blind, for 40 doses over 10 days.

Interventions: intervention 1: Ridinilazole intervention 2: Vancomycin
Intervention descriptions: intervention 1: Ridinilazole 200mg dosed BID for 10 days. intervention 2: Vancomycin 125mg dosed QID for 10 days.

Protocol document:
Prot_000.pdf: 
Study Number SMT19969-C006 
Ridinilazole 
Protocol 
Version 4.0, 12 Nov 2021 
CONFIDENTIAL 
Page 1 of 72 
Protocol Title: A Randomized, Double Blind, Active Controlled Study to Evaluate the Safety 
and Tolerability of Ridinilazole Compared with Vancomycin and to Assess the Pharmacokinetics 
of Ridinilazole in Adolescent Subjects (Aged 12 to <18 years) with Clostridioides difficile 
Infection  
Protocol Number: SMT19969/C006 
Protocol Amendment Number: 3 
Compound Number: SMT19969 (Ridinilazole) 
Short Title: Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent 
Subjects 
Sponsor Approval Date: 12 November 2021 
Regulatory Agency Identifying Number(s): IND No: 119,626 
 
EudraCT Number: 2021-006259-32 
 
 
Sponsor Name and Legal Registered Address:  
Summit Therapeutics, Inc. 
One Broadway, 14th Floor 
Cambridge MA 02142 
USA 
 
 
 
                                                              
 
 
The information contained in this document is the property of Summit Therapeutics, Inc. and may not be produced, 
published, or disclosed to others without written authorization from Summit Therapeutics, Inc. 


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Sponsor Signatory 
Priyanka Mandava 
Vice President, Global Clinical Operations 
Head of Clinical Operations 
Date 
Annie Hung, MA 
Executive Director, Biostatistics 
Study Statistician 
Date 
Lori Styles, MD 
Executive Medical Director 
Medical Science 
Date 
Medical Monitor Contact Information can be found in the Investigator Trial Site File. 


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Investigator Signature Page 
I agree to conduct this Study in accordance with the requirements of this document (the Clinical 
Study Protocol), the Study Reference Manual and in accordance with the following: 
• Declaration of Helsinki (revised version of Edinburgh, Scotland, 2000, Note of 
Clarification on Paragraph 29 added by the World Medical Association General 
Assembly, Washington 2002). 
• INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL 
• REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE (ICH): Guideline 
for GCP E6 (R2) 
• Any amendments to these regulations 
• Local laws and regulations. 
 
 
Investigator Name and Qualifications: 
 
 
 
Investigator Signature 
Date 


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Page 4 of 72 
Protocol Amendment Summary of Changes Table 
Note: Please refer to separate rationale of changes document for full explanation of and 
justification for protocol updates. 
DOCUMENT HISTORY 
Document 
Date 
Original Protocol Version 1.0  
(not submitted to any Competent Authority or EC/IRB) 
03 Sep 2020 
Amendment 1; Protocol Version 2.0 
Added the option to complete the 12-lead ECG assessment at screening or baseline 
17 Sep 2020 
Amendment 2; Protocol Version 3.0 
Minor typographical and formatting changes 
Changed sponsor name to Summit Therapeutics, Inc. 
Deletion of primary endpoint, secondary endpoint, and assessment of clinical 
response referenced below schema 
Format changes to stool sample, physical exam, and ECG rows to further emphasize 
assessments can be performed once between 2 visits, as per corresponding footnote 
Clarification on requirements for stool collections and that GI pathogen test is part 
of the standard diagnostic workup for patients who present with diarrhea 
Consistency of Clinical Cure definition provided across sections 
Clarification of instructions on IP return by patient to site 
Addition of sponsor name on IP label to include both Summit Therapeutics, Inc., 
and Summit (Oxford) Limited 
Change on instructions for patients in the event of a missed dose, to allow intake of 
missed dose prior to or concurrently with the next scheduled dose but no more than 
2 doses should be taken at any one time. 
Correction to text on the sponsor's use of previously collected patient data upon 
withdrawal of consent/assent 
Clarification on what data will be monitored by a DSMB 
Removal of compliance with GDPR 
Removal of registration in EU Clinical Trials Register 
03 Dec 2020 
Amendment 3; Protocol Version 4.0 
Minor typographical and formatting changes 
Inclusion criteria were updated to provide clearer instruction on stool sample 
eligibility 
Exclusion criteria were updated to provided clearer instruction and examples for 
confounding conditions and exclusions for bone marrow or hematopoietic stem cell 
transplantation were removed 
Edited concomitant medication rules to avoid the potential that needed medication 
might be withheld due to interpretation of disallowed concomitant medicines 
12 Nov 2021 


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DOCUMENT HISTORY 
Document 
Date 
Secondary endpoints of Clinical Response and Sustained Clinical Response, by 
Clinical Response, at 30-days post-End-of-Treatment was added to allow for 
extrapolation of results with the efficacy endpoint in the adult study 
Daily contact at EOT (including window) have been added to the study activities to 
capture data for the efficacy endpoint 


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TABLE OF CONTENTS 
SPONSOR SIGNATORY ...............................................................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................4 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
1.1. 
Synopsis ......................................................................................................................10 
1.2. 
Schedule of Activities (SoA) ......................................................................................15 
2. 
RATIONALE FOR STUDY ......................................................................................19 
2.1. 
Introduction .................................................................................................................19 
2.2. 
Background .................................................................................................................19 
2.3. 
Clostridioides difficile Infection in Children ..............................................................20 
2.4. 
Treatment ....................................................................................................................20 
2.5. 
Study Rationale ...........................................................................................................22 
2.6. 
Dose Justification of Study Medications ....................................................................22 
2.7. 
Benefit/Risk Assessment ............................................................................................23 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................25 
4. 
STUDY DESIGN .......................................................................................................27 
4.1. 
Subject Enrolment and Overall Design ......................................................................27 
4.2. 
End of Study Definition ..............................................................................................30 
5. 
STUDY POPULATION .............................................................................................31 
5.1. 
Inclusion Criteria ........................................................................................................31 
5.2. 
Exclusion Criteria .......................................................................................................32 
5.2.1. 
Subject Suitability .......................................................................................................33 
5.3. 
Lifestyle Considerations .............................................................................................33 
5.3.1. 
Meals and Dietary Restriction ....................................................................................33 
5.3.2. 
Caffeine, Alcohol, and Tobacco .................................................................................33 
5.3.3. 
Activity .......................................................................................................................33 
5.4. 
Screen Failures ............................................................................................................33 
6. 
STUDY TREATMENT ..............................................................................................34 
6.1. 
Administration of the Study Treatment ......................................................................34 
6.2. 
Preparation, Handling, Storage and Accountability ...................................................34 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................35 


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6.4. 
Study Treatment Compliance .....................................................................................36 
6.5. 
Concomitant Therapy .................................................................................................36 
6.5.1. 
Potential Confounding Medications ...........................................................................36 
6.6. 
Dose Modification ......................................................................................................38 
7. 
DISCONTINUATION OF STUDY TREATMENT AND WITHDRAWAL 
FROM STUDY ...........................................................................................................39 
7.1. 
Discontinuation of Study Treatment ...........................................................................39 
7.2. 
Withdrawal from Study ..............................................................................................39 
7.2.1. 
Withdrawal of Consent/Assent ...................................................................................40 
7.2.2. 
Lost to Follow Up .......................................................................................................40 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................41 
8.1. 
Safety Assessments .....................................................................................................41 
8.1.1. 
Medical History (Including CDI History) ..................................................................41 
8.1.2. 
Physical Examinations ................................................................................................41 
8.1.3. 
Vital Signs ..................................................................................................................42 
8.1.4. 
Electrocardiograms .....................................................................................................42 
8.1.5. 
Clinical Safety Laboratory Assessments ....................................................................42 
8.2. 
Adverse Events and Serious Adverse Events .............................................................43 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................43 
8.2.2. 
Method of Detecting AEs and SAEs ..........................................................................43 
8.2.3. 
Follow-up of AEs and SAEs .......................................................................................43 
8.2.4. 
Regulatory Reporting Requirements for SAEs ...........................................................44 
8.2.5. 
Events NOT Meeting the AE/SAE Definition: ..........................................................44 
8.2.6. 
Disease-Related Events Not Qualifying as AEs or SAEs ..........................................44 
8.3. 
Pregnancy ...................................................................................................................45 
8.4. 
Treatment of Overdose ...............................................................................................45 
8.5. 
Pharmacokinetics ........................................................................................................45 
8.5.1. 
Plasma PK Samples ....................................................................................................45 
8.5.2. 
Fecal PK Samples .......................................................................................................46 
8.6. 
Efficacy Assessments .................................................................................................46 
8.6.1. 
Assessment of Cure/Sustained Clinical Response ......................................................46 
8.6.2. 
Weekly Unformed Bowel Movement Contact ...........................................................47 
8.6.3. 
Daily Unformed Bowel Movement Contact ...............................................................47 


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8.6.4. 
Signs and Symptoms of CDI ......................................................................................47 
8.6.5. 
Suspected Recurrence .................................................................................................47 
8.6.5.1. 
Recurrence Visit .........................................................................................................48 
8.7. 
Stool (Feces) Collection for Future Research .............................................................49 
8.8. 
Pharmacodynamics .....................................................................................................49 
8.9. 
Genetics ......................................................................................................................49 
8.10. 
Biomarkers ..................................................................................................................49 
8.11. 
HEOR, Medical Resource Utilization ........................................................................50 
9. 
STATISTICAL CONSIDERATIONS .......................................................................51 
9.1. 
Sample Size Determination ........................................................................................51 
9.2. 
Populations for Analyses ............................................................................................51 
9.3. 
Statistical Analyses .....................................................................................................51 
9.3.1. 
Safety Analyses ..........................................................................................................51 
9.3.2. 
Pharmacokinetic Analyses ..........................................................................................52 
9.3.3. 
Efficacy Analyses .......................................................................................................52 
9.4. 
Interim Analyses .........................................................................................................52 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................53 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ......................53 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................53 
10.1.2. 
Financial Disclosure ...................................................................................................53 
10.1.3. 
Informed Consent/Assent Process ..............................................................................53 
10.1.4. 
Data Protection ...........................................................................................................54 
10.1.5. 
Dissemination of Clinical Study Data ........................................................................55 
10.1.6. 
Data Quality Assurance ..............................................................................................55 
10.1.7. 
Source Documents ......................................................................................................55 
10.1.8. 
Study and Site Closure ................................................................................................56 
10.1.9. 
Publication Policy .......................................................................................................56 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................57 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................58 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................64 


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10.5. 
Appendix 5: Bristol Stool Chart .................................................................................67 
10.6. 
Appendix 6 Abbreviations ..........................................................................................68 
10.7. 
References ...................................................................................................................71 
 
LIST OF TABLES 
Table 1: 
Dosing schedule per 24 hours (four doses) .................................................................34 
Table 2: 
Potentially Confounding Medications Which May Not Be Permitted During 
Study Treatment (Day 1 to Day 12 and/or during Follow-up (Day 12 to 
Day 100) .....................................................................................................................37 
Table 3: 
Protocol-Required Safety Laboratory Assessments ...................................................57 
Table 4: 
Highly Effective Contraceptive Methods ...................................................................65 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title 
A Randomized, Double Blind, Active-Controlled Study to Evaluate the Safety and Tolerability 
of Ridinilazole Compared with Vancomycin and Assess the Pharmacokinetics of Ridinilazole in 
Adolescent Subjects (Aged 12 to <18 years) with Clostridioides difficile Infection 
Short Title 
Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects  
Rationale 
Clostridioides difficile (formerly known as Clostridium difficile) Infection (CDI) is an infection 
of the colon that often develops following prior antibiotic use. An increase in the incidence of 
CDI in the pediatric population has been reported (Schutze, 2013). Although current standard 
treatments are effective with initial cure there is a considerable risk of recurrence, leaving the 
need for improved treatment options (Martin, 2016).   
Summit is developing ridinilazole as a novel antimicrobial for CDI with the goal of achieving 
comparable cure rates to standard of care but reducing rates of recurrent disease. A Phase 2 proof 
of concept study in adults, comparing ridinilazole with vancomycin (the current standard of 
care), demonstrated a lower recurrence rate for ridinilazole. The confirmation of this 
improvement is currently being investigated in two Phase 3 studies in adults. The rationale for 
the Phase 3 study described in this protocol is to evaluate the safety, tolerability and the 
pharmacokinetics of ridinilazole in subjects aged 12 to <18 years old with CDI. 
Objectives and Endpoints 
Primary Objectives 
• To assess the safety and tolerability of ridinilazole (200 mg bid), compared with 
vancomycin (125 mg qid), in adolescent subjects aged 12 to <18 years with 
Clostridioides difficile infection (CDI). 
• To assess the pharmacokinetics, including plasma and fecal concentrations, of 
ridinilazole in adolescent subjects aged 12 to <18 years with CDI. 
Secondary Objective 
• To assess the efficacy of ridinilazole (200 mg bid), compared with vancomycin 
(125 mg qid), in adolescent subjects with CDI. 


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Exploratory Objective 
• To explore the medical resource utilization of adolescent subjects with CDI being 
treated with ridinilazole 
Primary Endpoints 
• Incidence and severity of treatment-emergent adverse events 
• Plasma and fecal concentrations of ridinilazole 
Secondary Endpoints 
• Sustained clinical response (SCR) over 30 days post end of treatment (EOT) - defined 
as clinical cure at the assessment of cure (AOC) visit and no recurrence of CDI within 
30 days post EOT 
• Clinical cure at the AOC visit 
• Sustained clinical response over 60 days post EOT – defined as clinical cure at the 
AOC visit and no recurrence of CDI within 60 days post EOT 
• Sustained clinical response over 90 days post EOT – defined as clinical cure at the 
AOC visit and no recurrence of CDI within 90 days post EOT 
• SCR based on clinical response - defined as clinical response with no recurrence 
assessed through 30 days post-EOT 
• Clinical response at the AOC visit 
Exploratory Health Economics and Outcome Research (HEOR) Endpoint 
• Medical resource utilization and health economics endpoints 
Definitions 
Clinical cure 
The investigator assessment of clinical cure at the AOC visit is defined by the following: 
The resolution of diarrhea (< 3 unformed stools in a 1-day period) while on treatment, that is 
maintained until the AOC (EOT +2 days) visit, and no further requirement for further CDI 
antimicrobial therapy is needed through EOT + 2 days. 
Recurrence 
Recurrence is defined as a new episode of diarrhea and other signs and symptoms of C. difficile 
with a positive C. difficile free toxin test that requires CDI treatment. 


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Clinical response 
Clinical response is defined as:  
• less than 3 UBMs for 2 consecutive days and maintained through the EOT without further 
CDI antimicrobial treatment at EOT+2 days or  
• the investigator’s assessment that the subject no longer needs specific CDI antimicrobial 
treatment after completion of the course of study medication. 
Overall Design 
This is a Phase 3, multicenter, randomized, double blind, active-controlled, parallel group study 
designed to investigate the safety and tolerability of ridinilazole 200 mg bid, compared with 
vancomycin 125 mg qid, both administered for 10 days to adolescent subjects aged 12 to 
<18 years with CDI. The study will also assess the pharmacokinetics of ridinilazole, including 
plasma and fecal concentrations, in this population. Efficacy will be assessed as a secondary 
objective. 
Subjects must have the presence of toxin A and/or B of C. difficile in a stool sample as 
confirmed by a positive free toxin test using sponsor-approved assays. Suitable tests will have 
appropriate FDA approval. 
The study is comprised of a screening visit, a 10-day treatment period and a follow-up period of 
up to 90 days, to monitor safety and CDI recurrence. Following screening assessments and 
confirmation of eligibility, subjects will be randomized to receive ridinilazole or vancomycin in a 
3:1 fashion.  
An in-clinic or home visit will occur on Day 5 and a telephone check or clinic visit will be 
conducted at the end of treatment (EOT, Day 10). On Day 12, at least 48h after EOT, the AOC 
takes place and subjects will either attend an in-clinic visit, have a combined home/video visit or 
a videoconference visit with self-assessed vital signs (see Section 1.2, Schedule of Activities 
[SoA]). If the subject’s 10 days of dosing is completed on Day 11, the AOC visit will be 
conducted on Day 13. All subjects will remain in the study until at least Day 40, when they will 
have a study visit in the form of either an in-clinic visit, combined home/video visit or a 
videoconference visit with self-assessed vital signs (with help from guardian(s)). A daily UBM 
contact will occur at EOT -2, EOT -1, EOT, EOT +1, and EOT +2 to collect UBM data. 
Subsequently weekly telephone contact will be made with subjects until Day 40 and at Day 70 
and Day 100. 
Subjects not cured at AOC or experiencing recurrent CDI prior to or at Day 40, will receive 
standard-of-care in accordance with the Investigators’ clinical judgment and local practices. 
They will be encouraged to remain in the study and be monitored until Day 40. If the subject has 
a suspected recurrence prior to Day 40, the subject is to have either an in-clinic visit, a combined 
home/video visit or a videoconference visit with self-assessed vital signs for confirmation. 


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Those subjects cured at AOC and without a CDI recurrence by Day 40 will continue to be 
followed until Day 100 or recurrence (whichever comes earlier). If the subject has suspected 
recurrence after Day 40, the subject is to have either an in-clinic visit, a combined home/video 
visit or a videoconference visit with self-assessed vital signs for confirmation; if recurrent CDI is 
confirmed this visit will also serve as the subject’s end-of-study visit. If the subject remains free 
of recurrence, the end-of-study visit will be on Day 100. 
During the treatment period, subjects will be assessed for safety, tolerability, pharmacokinetics, 
and efficacy by reporting of clinical signs and symptoms, including adverse events, clinical 
laboratory assessments (including pharmacokinetics, chemistry and hematology), physical 
examinations, and vital signs. 
Note: the term “Investigator” refers to the Principal Investigator of the clinical site or a delegate 
as documented on the Delegation of Authority log. 
Number of Subjects 
The sample size has not been chosen on the basis of a formal hypothesis test. However, at least 
40 subjects (with a 3:1 allocation) are considered sufficient to investigate the safety of 
ridinilazole compared to vancomycin and approximately 30 subjects are sufficient to assess the 
pharmacokinetics of ridinilazole in this subject population.  
Key Inclusion/Exclusion Criteria 
Subjects aged 12 to <18 years are eligible to be included in the study if they meet the following 
criteria: 
• Has signs and symptoms of CDI, including diarrhea, such that, in the investigator’s 
opinion, CDI antimicrobial therapy is required, and the subject has tested positive for 
toxin A and/or B of C. difficile in the stool 
o Diarrhea is defined ≥3 UBMs based on types 5, 6, 7 on the Bristol stool chart and 
diarrhea information is within 24 hours prior to randomization 
Subjects are excluded from the study if any of the following criteria apply: 
• Has received treatments for CDI confounding with the study treatment as follows: 
o Has had more than the equivalent of 48 hours of dosing of antimicrobial treatment 
active against the current episode of CDI prior to randomization or  
o Has received ridinilazole or an investigational vaccine against C. difficile any time 
in the past; anti-toxin antibodies including bezlotoxumab within the past 
6 months; or any other investigational medicinal product for treatment of CDI or 
fecal microbiota replacement therapy within the past 3 months 
• Has a clinically relevant positive stool test for pathogens other than C. difficile, within 
48 hours of randomization 
• Has life-threatening or fulminant CDI with evidence of hypotension, septic shock, 
peritoneal signs or absence of bowel sounds, toxic megacolon, or ileus 


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• Has had major GI surgery (e.g., significant bowel resection or pancreatectomy, but not 
including appendectomy or cholecystectomy) within the past 3 months or has the 
presence of a colostomy or ileostomy or has the likely requirement of an ostomy during 
the study 
• Is receiving treatment that generally is associated with severe diarrhea, intractable 
vomiting, severe nausea, or inability to swallow that cannot be managed with antiemetics 
or antidiarrheals and that limits the ability to take oral medications. Cancer treatment that 
does not compromise ability to take study medication or cause severe diarrhea is allowed. 
Data and Safety Monitoring Board 
There is no plan to conduct a formal interim analysis. An independent DSMB will review 
unblinded safety data on a regular basis during the course of the study. Following each review, 
the DSMB will recommend action regarding the study (continue, continue with changes, 
temporarily stop or stop). The DSMB will comprise of 3 independent medical experts and an 
independent statistician. The specifics regarding the DSMB organization and procedures will be 
outlined in the DSMB Charter.  
Schema 
 
AOC = Assessment of Cure; EOT = End of Treatment; EOS = End of Study; SCR = Sustained Clinical Response 
Assessment 


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1.2. 
Schedule of Activities (SoA) 
Phase 
Screening 
Treatment Period 
Follow-Up Period 
Recurrence 
Day(D) 
D-3 to 
D11,3 
D11,2 
D53 
D103 
D124 ≥48 h 
from last dose 
D404 or early 
term pre-D40 
D703,5 
D1003,5 or early 
term post-D40 
Day 12 to 
D1004,5 
Assessment 
Screening 
Baseline 
Check-in 
End of 
Treatment 
Assessment of 
Cure 
Sustained Clinical 
Response 
Assessment 
Sustained Clinical 
Response 
Assessment 
Sustained Clinical 
Response 
Assessment 
Suspected 
Recurrence 
Visit window 
 
 
±1 day 
±1 day 
+ 3 days 
+5 days 
±5 days 
± 5 days 
≤48 h of 
identification 
Visit format 
Clinic/ 
Tel1,3 
Clinic/ HHC 
with VC1,2 
Clinic/ 
HHC with 
VC3 
Clinic/Tel3 
Clinic/ HHC/ 
VC4 
Clinic/ HHC/ VC4 
Clinic/Tel3 
Clinic/Tel3 
Clinic/ HHC/ 
VC4 
Written informed 
consent/assent6 
X 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
C. diff free toxin test7 
X 
 
 
 
 
 
 
 
X 
Medical/CDI history + 
prior/current 
medications8 
X 
X 
 
 
 
 
 
 
 
Stool sample9 
[X 
X]9 
 
X 
[X 
X]9 
X 
 
 
X 
Weekly UBM 
Review10 
 
 
 
 
X 
X 
 
Daily UBM Contact 
 
 
 
X11 
 
 
 
 
 
Height and Weight12 
X 
 
 
 
X 
X 
 
 
 
Physical exam and 
vital signs13 
[X 
X]13 
 
 
X 
X 
 
 
X 
12-lead ECG14 
[X 
X]14 
 
 
 
 
 
 
 
Blood samples 
(hematology and 
clinical chemistry) 
 
X 
 
 
X 
X 
 
 
 


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Phase 
Screening 
Treatment Period 
Follow-Up Period 
Recurrence 
Day(D) 
D-3 to 
D11,3 
D11,2 
D53 
D103 
D124 ≥48 h 
from last dose 
D404 or early 
term pre-D40 
D703,5 
D1003,5 or early 
term post-D40 
Day 12 to 
D1004,5 
Assessment 
Screening 
Baseline 
Check-in 
End of 
Treatment 
Assessment of 
Cure 
Sustained Clinical 
Response 
Assessment 
Sustained Clinical 
Response 
Assessment 
Sustained Clinical 
Response 
Assessment 
Suspected 
Recurrence 
Visit window 
 
 
±1 day 
±1 day 
+ 3 days 
+5 days 
±5 days 
± 5 days 
≤48 h of 
identification 
Visit format 
Clinic/ 
Tel1,3 
Clinic/ HHC 
with VC1,2 
Clinic/ 
HHC with 
VC3 
Clinic/Tel3 
Clinic/ HHC/ 
VC4 
Clinic/ HHC/ VC4 
Clinic/Tel3 
Clinic/Tel3 
Clinic/ HHC/ 
VC4 
Urine pregnancy test 
(dipstick) for 
WOCBP15 
 
X 
 
 
X 
X 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
IMP Dosing  
(four times daily for 
10 days)16 
 
 
 
 
 
 
 
Signs and symptoms of 
CDI 
 
X 
 
X 
X 
 
 
 
X 
Investigator assessment 
of cure/sustained 
clinical response17 
 
 
 
 
X 
X 
X 
X 
X 
PK Stool Sample18 
 
X 
X 
 
 
 
 
 
 
PK Blood Sample 
(4 hours post dose)19 
 
X 
X 
 
 
 
 
 
 
Medical resource 
utilization questions 
 
X 
 
 
X 
X 
X 
X 
X 
Concomitant 
medications 
 
AE reporting20 
 
 
 
X 
SAE reporting 
 
Note: Unscheduled telephone calls and/or visits may be conducted, if necessary, for the subject’s safety. 


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Numbered notes: 
1. Screening and D1/baseline assessments may occur on the same day or within a 1 to 3-day window. Subjects can be rescreened once for this study.   
2. Preferably the Baseline visit should be completed as an in-clinic visit; however, to maximize potential enrolment (e.g., during a pandemic) the visit may 
be conducted remotely. If so, a sponsor-contracted home healthcare vendor or properly trained and delegated site staff must conduct assessments at the 
subject’s home. The Investigator will join by video conference to perform their assessments. All assessments should be completed prior to 
randomization except for the following, which must still be conducted prior to their 1st dose of study medication: weight, blood samples (hematology 
and clinical chemistry), stool collection (if required, to collect a sample for microbiology/microbiome that is <24h old), and medical resource utilization 
questions.   
3. The Day 5 visit will preferably be an in-clinic visit; however, if this is not appropriate (e.g., during a pandemic) a sponsor-contracted home healthcare 
vendor or properly trained and delegated site staff can conduct assessments and collect samples at the subject’s home. The visits for screening, D10, 
D70 and D100 may be conducted in-clinic or by telephone. If Day 10 conducted by telephone, stool sample drop off or collection of the sample from the 
subject’s home must be arranged.  
4. D12, D40 and recurrence visits are preferably in-clinic visits; however, these visits may be conducted remotely. If so, the following approaches may be 
taken: 
a. 
if the subject has been provided with vital sign equipment by the site, the visit may be conducted with only a video conference between the 
Investigator and the subject in the presence of a guardian.  
b. a sponsor-contracted home healthcare vendor or properly trained and delegated site staff may conduct the visit at the subject’s home with a 
guardian present and with the Investigator joining by video conference 
5. Subjects who are cured at AOC and have SCR at Day 40 will continue to be followed until Day 100 or recurrence (whichever comes earlier).  
6. Documented informed consent/assent must be provided by the subject/guardian prior to any study procedure being conducted. Electronic consent 
(eConsent) should be used; however, subject may sign a paper consent form when the screening visit is performed in-clinic.  If the visit is performed 
remotely and the subject cannot adhere to eConsenting, they may receive an email copy of the consent/assent form and carry out a synchronous consent 
discussion over the phone.  
7. Free Toxin Test: sites may use an established local free toxin test laboratory service if it is a suitable test and is prospectively agreed with the Sponsor. 
Suitable tests will have appropriate regulatory approvals (FDA approval). Subjects with a negative free toxin test will be excluded from the study. 
Suspected recurrence: the local free toxin test (FTT) must be conducted as soon as possible and at a maximum of 48 hours after identifying a suspected 
recurrence. Cell Cytotoxicity Neutralization Assay (CCNA) will be conducted at a specialized central laboratory for negative free toxin tests. 
a. 
Negative or invalid free toxin test results: A negative free toxin test may be repeated once for baseline and suspected recurrence. The same 
sample may be used if collected within 24 hours, otherwise a fresh sample must be used. Invalid test results should be repeated. 
8. Record all known historical CDIs along with associated treatment, information on the baseline CDI including signs and symptoms, any potential 
confounding medications taken up to 4 weeks prior to randomization, relevant medical history and all prior and current medications taken up to 4 weeks 
prior to randomization. 
9. Stool samples should be aliquoted and frozen within 24 hours of sample being produced. Aliquots should be sent to the Central Laboratory. Only one 
sample is required at either Screening or D1. Only one sample is required at either D10 or D12. One other sample is required at D40. An additional stool 
sample is required at recurrence. If the visit is conducted remotely, stool sample drop off or collection from the subject (e.g., courier) must be arranged. 


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a. 
Screening: GI pathogen test (as part of standard diagnostic workup) and C. diff toxin test.  Suspected recurrence: C. difficile toxin test (refer to 
footnote 7). All stool samples: sample should be aliquoted and frozen within 24 hours of sample being produced where possible and sent to the 
central laboratory for future research. 
10. Weekly Unformed Bowel Movement (UBM) Contact: Weekly telephone contact will be made with subjects until Day 40, and thereafter on Day 70 and 
Day 100. Over the daily UBM contact period, it is not necessary to conduct separate weekly phone calls.  
11. Daily Unformed Bowel Movement (UBM) Contact: Daily contact (either by telephone or in clinic) to collect the total number of UBMs in a 1-day 
period at the following timepoints: EOT -2 days, EOT -1 day, EOT, EOT +1 and EOT +2. Contacts should be made +/- 2 days of the expected EOT 
timepoint. 
12. Height will be collected at screening only. 
13. Vital signs include blood pressure, pulse, and body temperature. The physical exam may be conducted at the screening or baseline visit; if conducted at 
screening, the vital sign assessment will still need to be repeated at baseline. 
14. ECG: The ECG may be performed at the screening or baseline visit. The ECG does not need to be performed if most recent ECG was normal (using the 
parameters and qualifications mentioned in Section 8.1.4) and was done in the 12 months prior to randomization. 
15. Post-menarche female subjects testing to be performed on D1 and D12. Testing in the case of missed menses should also be conducted up to 30 days 
following the last dose of study treatment. 
16. Subjects who have discontinued study drug early should remain in the study and be monitored, e.g., for adverse events. 
17. Clinical response is defined as less than 3 UBMs for 2 consecutive days and maintained through the EOT without further CDI antimicrobial treatment at 
EOT+2 days or the investigator’s assessment that the subject no longer needs specific CDI antimicrobial treatment after completion of the course of 
study medication. The investigator assessment of clinical cure at the AOC visit is defined by the following: The resolution of diarrhea (< 3 unformed 
stools in a 1-day period) while on treatment, that is maintained until the AOC (EOT +2 days) visit, and no further requirement for further CDI 
antimicrobial therapy is needed through EOT + 2 days. Recurrence is defined as a new episode of diarrhea with a positive C. difficile free toxin test that 
requires CDI antimicrobial treatment. Sustained Clinical Response is defined as clinical response with no recurrence assessed through 30 days post- 
EOT. 
18. A PK Stool Sample will be collected on Day 1 (after dosing) or Day 2, and on Day 5 or Day 6. If the day of last dose is prior to Day 5, stool sampling is 
to be done on that last dosing day. 
19. One blood PK sample will be collected at approximately 4 hours (+ 1 hour) post-dose on Day 1 or Day 2 (following either Dose 1, 3, 5 or 7) and Day 5 
or Day 6 (following either Dose 17, 19, 21 or 23), or the subject’s last ‘odd’ dose of study treatment (if earlier than Day 5). An accurate date and time of 
dose and sampling is required.  
a. 
A home healthcare vendor or appropriately trained and delegated site staff may perform this procedure at the subject’s home. 
20. AEs only need to be reported up to the D40 visit. AE’s meeting the definition of serious should be reported throughout the study. Recurrence Visit: 
AE’s to be reviewed if the recurrence is before D40. 
 


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2. 
RATIONALE FOR STUDY 
2.1. 
Introduction 
Clostridioides difficile (formerly known as Clostridium difficile) Infection (CDI) is an infection of 
the colon that invariably develops following prior antibiotic use. An increase in the incidence of 
CDI in the pediatric population has been reported (Schutze, 2013). Recurrence of CDI occurs in 
up to 30% of pediatric patients following initial therapy, hence the prevention of recurrent disease 
remains a key unmet medical need in the management of CDI (Nicholson, 2017). Each episode of 
recurrent disease is associated with an increased risk of further recurrent episodes placing a 
significant burden on patients through increased morbidity and diminished quality of life. 
Identified risk factors for recurrence of CDI in children include malignancy, recent surgery, 
antibiotic exposures, and the presence of a tracheostomy tube (Sammons, 2013; El Feghaly, 2013). 
While administration of standard CDI antibiotics (vancomycin or metronidazole) may result in a 
reduction in C. difficile and subsequent relief of symptoms, these antibiotics have been shown to 
have ongoing and deleterious effects to the gut microbiome. As such, repeated courses of treatment 
for CDI may exacerbate the situation with ongoing disturbance of the microbiome leaving patients 
prone to further episodes of CDI. Therefore, therapeutic approaches that allow restoration of the 
gut towards a normal microbiome and resistance to C. difficile colonization, especially with narrow 
spectrum C. difficile-targeted antibiotics, are expected to reduce rates of recurrent disease. 
Summit is developing ridinilazole which is associated with a highly targeted activity that has been 
shown to result in minimal collateral impact on the gut microbiota during therapy; therefore, it is 
expected that treatment with ridinilazole will lead to reduced rates of CDI recurrence. Reduced 
risk of recurrence was demonstrated in a Phase 2 proof of concept study in adults where superior 
efficacy was observed with ridinilazole treatment compared to vancomycin. There was a marked 
reduction in rates of CDI recurrence (ridinilazole: 14% recurrence; vancomycin: 36%) and hence 
improved sustained clinical response rates (Vickers, 2017). 
Nonclinical and prior clinical studies have shown that ridinilazole is retained in the gastrointestinal 
(GI) tract following oral dosing, therefore maximizing exposure of ridinilazole at the site of 
infection and minimizing systemic exposure. A detailed description of the chemistry, 
pharmacology, efficacy, and safety of ridinilazole is provided in the Investigator’s Brochure. 
2.2. 
Background 
C. difficile is an anaerobic Gram-positive spore-forming species of bacteria which is responsible 
for epidemics and individual cases of CDI, with symptoms ranging from mild, self-limiting 
diarrhea to more severe and potentially life-threatening manifestations such as pseudomembranous 
colitis and toxic megacolon (Smits, 2016). 
C. difficile can often be a harmless resident of the GI tract with levels typically kept in check by 
the complex community of microorganisms that make up the indigenous gut microbiota and 
metabolome. However, disruption to the healthy ecological balance of the gut, typically by 
antibiotic use, diminishes the ability of the host to resist germination of spores and colonization 
by C. difficile, leading to toxin production and disease symptoms (Rupnik, 2009; Kelly, 2008). 


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CDI is a leading cause of nosocomial infectious diarrhea in adults (Smits, 2016). It is recognized 
as a significant concern within the healthcare system and is increasingly becoming a recognized 
issue in the community as well. Currently, up to 30% of patients who are treated for an initial 
episode of CDI experience a recurrence of infection once therapy is discontinued. This recurrence 
can occur within days or weeks of completing initial treatment. The risk of recurrence increases 
with each episode; following a second recurrence, 40% to 60% of patients may experience a 
subsequent episode (Kelly, 2012). 
2.3. 
Clostridioides difficile Infection in Children 
C. difficile clearly has a pathogenic role in adults and older children. However, in infants and 
neonates, C. difficile is more commonly found as a commensal organism and is recovered from an 
average of 37% (range 25% to 80%) of stools from healthy infants <1 month of age. Colonization 
rates fall slightly to an average of 30% by 6 months of age and to approximately 10% by 1 year of 
age. By the time a child reaches approximately 3 years of age, the colonization rate is similar, at 
approximately 0% to 3%, to that of asymptomatic adults (Schutze, 2013; Jangi, 2010). 
An increase in the incidence of CDI in the pediatric population has been reported, especially in 
those children who are hospitalized but also in the community setting (Schutze, 2013; 
Sammons, 2013). 
CDI in children is typically associated with co-morbidities such as underlying gastrointestinal 
disease (e.g., IBD), gastrointestinal surgery, renal insufficiency, and malignancy (El-Matary, 
2019). Of note is the association of gastrointestinal disease, such as IBD or Hirschsprung’s disease, 
with pediatric CDI (Kim, 2018). 
2.4. 
Treatment 
The most recent Infectious Diseases Society of America (IDSA) guidelines on the treatment of 
CDI include specific recommendations for the treatment of pediatric patients (McDonald, 2018). 
Metronidazole or vancomycin are recommended for treatment of a first episode or first recurrence 
of non-severe CDI. In severe disease and in cases of second recurrences, oral vancomycin is 
recommended over metronidazole (El Feghaly, 2013). 
Fidaxomicin was recently approved in the US and European Union (EU) for the treatment of 
Clostridioides difficile-associated diarrhea (CDAD) and has been shown to be non-inferior on 
clinical response to vancomycin at the end of treatment and superior to vancomycin on sustained 
clinical response to 28 days post end of therapy. However, fidaxomicin was not shown to be 
superior to vancomycin on sustained clinical response for patients infected with BI/NAP1/027 
strains (Louie, 2011; Cornely, 2012). 
Since the IDSA guidelines have been published, data on fidaxomicin in children have been 
published. One study in 38 patients has been completed with fidaxomicin in the pediatric 
population where fidaxomicin was demonstrated to be well tolerated (Sears, 2014). Overall, the 
early clinical response rate was 92.1%. and the rate of sustained clinical response through 28 days 
after treatment was 65.8% (O'Gorman, 2018). Subsequently, in a Phase 3 study in pediatric 
patients, the clinical response rates were 77.6 % (76/98) and 70.5% 931/41 for fidaxomicin and 
vancomycin respectively. Global cure (end of therapy cure and no recurrence at 30 days) rates 
were 68.4% (67/98) and 50% (22/44) respectively (Wolf, 2019). 


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As fidaxomicin was not approved for use in pediatric patients at the time of compiling the most 
recent IDSA guidelines, no recommendation on its use was made. Recently, FDA approved the 
use of fidaxomicin in the pediatric population (aged 6 months to <18 years; January 2020). 
Given the paucity of therapeutic options that reduce the risk of recurrence of CDI and the increased 
incidence of CDI in children, there continues to be an unmet medical need for improved 
antimicrobial treatment in the pediatric population including those who are undergoing antibiotic 
therapy, suffer IBD, or who have immunodeficiency, a poor diet, super-infections, cancer, or 
similar comorbidities (Ghose, 2013). 
Ridinilazole is being developed with the objective to reduce the risk of recurrence of CDI. A 
Phase 2 randomized, double blind, active comparator study (SMT19969/C002) conducted in 
100 adult patients with CDI comparing the safety and efficacy of ridinilazole 200 mg bis in die 
(bid) for 10 days versus the approved dose of vancomycin 125 mg quarter in die (qid) in the 
treatment of CDI has been completed. In the modified intent to treat population (confirmed 
diagnosis with positive free toxin test) the incidence of recurrence was 14.3% for ridinilazole- 
treated patients and 34.8% for vancomycin-treated patients, contributing to the sustained clinical 
response (clinical response at test of cure and no recurrence in 30 days) rates of 24/36 (66.7%) and 
14/33 (42.4%) for patients on ridinilazole and vancomycin, respectively. The estimated difference 
of 21.2% (90% CI: 3.1%, 39.1%) between the two groups indicated superiority of ridinilazole 
compared to vancomycin at the pre-specified 10% level of significance. Furthermore, ridinilazole 
tested non-inferior for cure compared to vancomycin (cure rate for ridinilazole 77.8%, for 
vancomycin 69.7%) (Vickers, 2017). 
In addition, the study showed that ridinilazole was well tolerated, with an adverse event profile 
comparable to that of vancomycin. In the safety population (all treated patients), 82% (41/50) and 
80% (40/50) in the ridinilazole and vancomycin groups, respectively, reported adverse events, 
while 16% (8/50) and 18% (9/50) of patients in the respective groups reported serious adverse 
events. There were no study drug-related adverse events that led to discontinuation in the 
ridinilazole group. Full details of the study results are provided in the Investigators Brochure. 
An exploratory Phase 2, multi-centre, open-label, randomized, active-controlled, parallel-group 
study in adults (SMT19969/C003) was conducted to evaluate the safety and tolerability of 10 days 
of dosing with ridinilazole (200 mg bid) compared with fidaxomicin (200 mg bid). A total of 
27 patients (14 ridinilazole: 13 fidaxomicin) were randomized to study treatment and all were 
included in the safety and efficacy analysis populations. Sustained clinical response was 
comparable between the ridinilazole group (50.0%) and the fidaxomicin group (46.2%) with an 
overall treatment difference of 2.9% (95% CI: -30.8%, 36.7%). The ridinilazole group had a higher 
proportion of patients with risk factors for CDI recurrence than fidaxomicin including concomitant 
antibacterial use, severe disease, and age ≥65 years. 
Overall, ridinilazole was considered safe and generally well tolerated. All patients in the safety 
population, except two patients in the fidaxomicin group, experienced treatment-emergent adverse 
events (TEAEs). The majority of TEAEs were mild in severity and resolved without treatment and 
there were no discontinuations due to TEAEs. 


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Analysis of the microbiome of the patients showed that ridinilazole was associated with reduced 
negative impact on the indigenous microbiota as measured through reduced alpha-diversity and 
changes in major taxa identified via 16S rRNA sequencing. Full details of the study results are 
provided in the Investigators Brochure. 
2.5. 
Study Rationale 
As discussed above, there is an unmet medical need for improved treatment options in children 
with CDI. Ridinilazole is being developed by Summit for the use in the pediatric population. 
Ridinilazole is a novel antibiotic currently being investigated for the treatment of CDI and reducing 
the recurrence of CDI in adults. Ridinilazole has been shown to exert potent growth inhibition with 
a narrow minimum inhibitory concentration (MIC) range against a broad range of C. difficile 
ribotypes collected from both the US and Europe. This includes hyper virulent ribotypes such as 
027 and isolates showing reduced susceptibility to vancomycin and metronidazole. Ridinilazole is 
a non-absorbed and effective GI drug, with a narrow spectrum of activity; typically, >1000-fold 
selectivity for C. difficile over Gram-positive and Gram-negative anaerobic and facultative 
members of the gut microbiota. This feature of ridinilazole has been shown to result in minimal 
collateral damage to the gut microbiota compared with vancomycin (Thorpe, 2018), giving it a 
very good safety profile and excellent tolerability throughout the course of treatment of CDI during 
a Phase 2 clinical trial, and ultimately led to a marked reduction in rates of recurrent CDI. 
The primary objective of this study is the evaluation of the safety and tolerability of ridinilazole in 
adolescents with CDI. The safety results of the Phase 2 studies and the currently ongoing Phase 3 
studies have demonstrated a benign safety profile to date. Similarly, animal toxicology studies 
showed few adverse events. This benign safety profile probably relates to the very limited systemic 
exposure of ridinilazole. Prior adult studies have indicated that most plasma samples from adult 
humans are near or below the limit of quantification of the assay. To further assess and confirm 
the low systemic exposure in adolescents, the current study will collect one PK sample at 
approximately 4 hours (±1 hour) post-dose on Day 1 (or 2) and Day 5 (or 6), or on the day of the 
subject’s last dose of study medication if earlier. 
2.6. 
Dose Justification of Study Medications 
Vancomycin 
The most recent IDSA guidelines on the treatment of CDI include specific recommendations for 
the treatment of pediatric patients (McDonald 2018). Metronidazole is only recommended for 
treatment of a first episode or first recurrence of non-severe CDI. In contrast, vancomycin or 
fidaxomicin are recommended for all disease severities, based on data showing metronidazole to 
be inferior to vancomycin across all disease severities in adults (Johnson 2014). However, the 
IDSA guidelines note the lack of comparative data between vancomycin and metronidazole in 
pediatric patients and consequently make no specific recommendation of using vancomycin over 
metronidazole in non-severe disease in pediatric patients. In severe disease and in cases of second 
recurrences, oral vancomycin is recommended over metronidazole. As such, Summit will use 
125 mg of vancomycin dosed four times daily as the active comparator in the Phase 3 adolescent 
study. 


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Ridinilazole 
In a Phase 2 study in adults, 50 patients were administered ridinilazole 200 mg bid for 10 days for 
treatment of CDI. The dose was shown to be safe and well-tolerated and demonstrated superiority 
in sustained clinical response over vancomycin at the 10% level of significance (2-sided test). 
At this dose there was negligible systemic exposure of ridinilazole with mean (SD) plasma 
concentrations of 0.06 (0.11), 0.16 (0.26), and 0.18 (0.22) ng/mL at nominal 4 hours post-dose on 
Days 1, 5, and 10, respectively. Furthermore, there was no notable effect on systemic exposure 
due to food, gender, concomitant medication, age, or disease severity. Corresponding fecal 
concentrations of drug (Day 10 mean =1,373 µg/g) were significantly above the MIC90 value of 
0.125 µg/mL for C. difficile. 
Additionally, ridinilazole demonstrated negligible absorption in healthy adult volunteers. Provided 
there is similarly negligible absorption of ridinilazole from the gut in adolescents and local gut 
toxicity in adolescents is similar to that observed in adults, the adult dose of 200 mg is also 
considered suitable to adolescents. 
2.7. 
Benefit/Risk Assessment 
In 28-day oral toxicity studies in rats and dogs up to ridinilazole 1000 mg/kg/day no adverse study 
findings were seen with associated plasma levels below the lower limit of quantification (LLOQ). 
Assessment of the systemic toxicity of ridinilazole for 28 days by the i.v. route in the rat and the 
dog identified the liver, lungs (findings possibly caused by particulate deposition of ridinilazole in 
capillary beds due to plasma saturation), spleen and kidneys (rat only), thymus and gall bladder 
(dog only) as target organs from a dose-level of ridinilazole 0.5 mg/kg/day. The associated 
ridinilazole plasma levels were several hundred-fold higher than the plasma levels observed in 
humans so far. 
In a Phase 1 study, 42 healthy male subjects received single oral doses of up to 2000 mg in the 
fasted state, a single oral dose of 1000 mg in the fed state or repeated doses at up to 500 mg bid 
for 9 days in the fed state, with ridinilazole being considered safe and well tolerated. The most 
frequent drug-related AEs were classified as GI disorders: diarrhea and abdominal distension/pain. 
In Phase 2 studies a total of 64 patients (SMT19969/C002 50 patients; SMT19969/C003 
14 patients) received ridinilazole 200 mg bid with no additional safety signals observed. The 
most frequent AEs were GI related. The safety profile of ridinilazole in Study SMT19969/C002 
was comparable to the comparator, vancomycin, which will be used in this proposed study. 
In the Phase 2 study SMT19969/C002 ridinilazole was shown to be superior at the pre-specified 
10% level of significance (2-sided test) over standard of care vancomycin with respect to its 
primary endpoint of SCR and non-inferior with respect to its key secondary endpoint at AOC. 
In Study SMT19969/C003 ridinilazole displayed comparable clinical efficacy to fidaxomicin on 
sustained clinical response (SCR). 
In both Phase 2 clinical studies the plasma concentrations of ridinilazole were either below or close 
to the LLOQ, with a maximum systemic concentration of 1.31 ng/mL across all patients and 
assessment days. Therefore, GI related local tolerability AEs can be expected to be the main 
potential safety risks for ridinilazole. 


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Although this will be the first-time adolescent patients are evaluated with this drug, it is expected 
that the maturity of the GI tract in this age group will be comparable to adults and as such the 
safety profile and the tolerability should be comparable to adults. However, this will need to be 
monitored carefully during the duration of the trial, particularly in view of the multiple 
comorbidities that these patients may have, including cancer, cystic fibrosis, and inflammatory 
bowel disease (IBD). 
Together with non-clinical data showing ridinilazole has a narrow spectrum activity against 
C. difficile and microbiome sparing properties, these clinical data are considered to provide a 
positive benefit-risk profile for subjects in this study. Safety procedures during this clinical trial 
consist of vital signs, physical examinations, and laboratory assessments. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of ridinilazole may be found in the Investigator’s Brochure. A risk 
assessment for vancomycin can be found in the package insert. 
Summit Therapeutics believes it is important to continue developing ridinilazole for patients with 
CDI while ensuring the safety of study subjects, study personnel, and the public during 
Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-COV-2. We have carefully 
assessed the Ri-CoDIFy studies in the context of the COVID-19 pandemic. Both CDI and 
COVID-19 are emerging infections that occur in at-risk populations (e.g., those with pre-existing 
medical conditions) and can result in significant morbidity and mortality. Like SARS-COV-2, 
Clostridioides difficile is a transmissible pathogen and infection rates may be lower initially with 
the recent implementation of COVID-19 public health actions. However, antibacterial treatments 
used empirically when a patient is being assessed with a respiratory infection or complicated by 
post-COVID-19 bacterial pneumonias could lead to an increase in CDI infections and associated 
changes to the gut microbiome. New therapies for CDI that are effective, safe and have lower post- 
treatment recurrences are needed. 


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3. 
OBJECTIVES AND ENDPOINTS 
Primary Objectives 
• To assess the safety and tolerability of ridinilazole (200 mg bid), compared with 
vancomycin (125 mg qid), in adolescent subjects aged 12 to <18 years with 
Clostridioides difficile infection (CDI). 
• To assess the pharmacokinetics, including plasma and fecal concentrations, of 
ridinilazole in adolescent subjects aged 12 to <18 years with CDI. 
Secondary Objective 
• To assess the efficacy of ridinilazole (200 mg bid), compared with vancomycin 
(125 mg qid), in adolescent subjects with CDI. 
Exploratory Objective 
• To explore the medical resource utilization of adolescent subjects with CDI being 
treated with ridinilazole 
Primary Endpoints 
• Incidence and severity of treatment-emergent adverse events 
• Plasma and fecal concentrations of ridinilazole 
Secondary Endpoints 
• Sustained clinical response (SCR) over 30 days post end of treatment (EOT) - defined 
as clinical cure at the assessment of cure (AOC) visit and no recurrence of CDI within 
30 days post EOT 
• Clinical cure at the AOC visit 
• Sustained clinical response over 60 days post EOT – defined as clinical cure at the 
AOC visit and no recurrence of CDI within 60 days post EOT 
• Sustained clinical response over 90 days post EOT – defined as clinical cure at the 
AOC visit and no recurrence of CDI within 90 days post EOT 
• SCR based on clinical response - defined as clinical response with no recurrence 
assessed through 30 days post-EOT 
• Clinical response at the AOC visit 
Exploratory Health Economics and Outcome Research (HEOR) Endpoint 
• Medical resource utilization and health economics endpoints 


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Definitions 
Clinical cure 
The investigator assessment of clinical cure at the AOC visit is defined by the following: 
The resolution of diarrhea (< 3 unformed stools in a 1-day period) while on treatment, that is 
maintained until the AOC (EOT +2 days) visit, and no further requirement for further CDI 
antimicrobial therapy is needed through EOT + 2 days. 
Recurrence 
Recurrence is defined as a new episode of diarrhea and other signs and symptoms of C. difficile 
with a positive C. difficile free toxin test that requires CDI treatment. 
Clinical response 
Clinical response is defined as:  
• less than 3 UBMs for 2 consecutive days and maintained through the EOT without further 
CDI antimicrobial treatment at EOT+2 days or  
• the investigator’s assessment that the subject no longer needs specific CDI antimicrobial 
treatment after completion of the course of study medication. 


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4. 
STUDY DESIGN 
4.1. 
Subject Enrolment and Overall Design 
Enrollment 
SMT19969/C006 is a randomized, double blind, active-controlled study to evaluate the safety 
and tolerability of ridinilazole compared with vancomycin and to assess the pharmacokinetics of 
ridinilazole in adolescent subjects (aged 12 to <18 years) with Clostridioides difficile infection. 
At least 40 subjects with a confirmed diagnosis of CDI will be randomized into the study. 
The study includes a screening visit, a 10-day treatment period (beginning on the day of 
screening or the following day) and up to 90-day follow-up period. 
Due to the acute nature of CDI and typical requirement for immediate treatment it is expected 
that the screening and the baseline/Day 1 assessments will be conducted on the same day, but it 
is allowed to conduct the screening visit within 3 days prior to the baseline/Day 1 visit if 
required for practical reasons. Due to the potential impact of the COVID-19 pandemic, there is 
flexibility built into the protocol to allow all study visits to be completed remotely, however, 
subjects should continue to attend in-clinic visits wherever possible. 
Study Periods 
Randomization will occur after confirmation of eligibility is established at the 
Screening/Baseline clinic visit. Subjects will be randomized to receive ridinilazole or 
vancomycin in a 3:1 ratio.  
Dosing with study treatment starts on Day 1 continuing for 10 days. Another in-clinic visit 
(or alternative, see the SoA) will be scheduled at Day 5 (or 6) in order to collect samples for PK 
analysis. A telephone check or clinic visit will be conducted at Day 10 to confirm completion of 
study treatment, end of treatment (EOT). At Day 12, at least 48h after EOT, there is an in-clinic 
visit (or alternative, see the SoA) for Assessment Of Cure (AOC). If the subject's 10 days dosing 
is completed on Day 11, the EOT + 2 days visit will be conducted on Day 13. A daily UBM 
contact will occur at EOT -2, EOT -1, EOT, EOT +1, and EOT +2 to collect UBM data. 
Subsequently there are weekly telephone checks until Day 40 and at Day 70 and Day 100.  
All subjects will remain in the study until at least Day 40, when they will attend an in-clinic visit 
(or alternative, see the SoA). Subjects not cured at AOC or experiencing recurrent CDI prior to 
or at Day 40, will receive standard-of-care in accordance with the investigators’ clinical 
judgment and local practices for treatment of their CDI. Subjects not cured at the AOC visit or 
having recurrence nevertheless must remain in the study and be monitored, e.g., for adverse 
events, until Day 40. Those subjects cured at AOC and without a CDI recurrence by Day 40 will 
continue to be followed until Day 100 or recurrence (whichever comes earlier). If the subject has 
suspected recurrence after Day 40, the subject should make an in-clinic visit (or alternative, see 
the SoA) for confirmation and for providing a stool sample; if recurrent CDI is confirmed this 
visit will also serve as the subject’s end of study visit. Following Day 40, a telephone call to 
check for CDI recurrence will be made on Day 70. If the subject remains free of recurrence, 
he/she will have the end of study visit at Day 100 either by a telephone call or clinic visit.  


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All subjects considered cured at AOC who experience suspected CDI recurrence are expected to 
provide a stool sample for free toxin testing no later than 48 hours after identifying the suspected 
recurrence. Details on the timing of treatment and assessments are given in the Schedule of 
Activities Table (Section 1.2). 
PK plasma sampling will occur on Day 1 or Day 2 and on Day 5 or Day 6. If the last day of 
dosing with study medication occurs prior to Day 5, the sample is to be taken on the last dosing 
day. The PK fecal (stool) samples will be collected on Day 1 (after dosing) or Day 2 and on 
Day 5 or Day 6. If the last day of dosing with study medication occurs prior to Day 5, the sample 
is to be taken on the last dosing day.   
Unscheduled visits may occur at the Investigator’s discretion (e.g., in the case of AEs) and 
subjects should be requested to attend for a recurrence visit (or alternative, see the SoA) in the 
event of suspected recurrences of CDI. Of note, the term “Investigator” refers to the Principal 
Investigator of a clinical site or a delegate as documented on the site Delegation of Authority log. 
COVID-19 
Where possible, it is preferred for visits with an in-clinic option to be done in-clinic, especially 
the highly complex baseline visit, however, subjects may need to carry out one or more study 
visits remotely to ensure their safety during the global COVID-19 pandemic. Modifications for 
subjects needing remote visits include: 
Screening visit 
The assent process (informed consent process) should be captured electronically via eConsent 
with an impartial witness, however, subjects may sign a paper consent form when the screening 
visit is conducted in-clinic. If the visit has to be conducted remotely and the subject cannot 
adhere to eConsenting, they may have the consent/assent form(s) emailed to them and carry out a 
synchronous consent discussion over the phone. Consent/assent form(s) must be received and 
acknowledged by the site prior to the commencement of any study procedures. The original 
signed consent/assent form(s) must be returned to the site either at the next in-clinic visit, posted 
to the site, or returned via courier or any other approved alternate method. The stool sample may 
be couriered to the site. 
The ECG and physical exam may be conducted at the screening visit to allow the subject to 
return home while awaiting FTT results. If the physical exam is conducted at screening, the vital 
sign assessment will still need to be repeated at baseline. An ECG does not need to be performed 
if most recent ECG was normal (using the parameters and qualifications mentioned in 
Section 8.1.4 ) and was done in the 12 months prior to randomization. 
Baseline visit 
A sponsor contracted home healthcare vendor or appropriately trained and delegated site staff 
may assist with the baseline visit in extreme cases where the subject is unable to complete the 
visit in- clinic for safety reasons. 
The home healthcare vendor or site staff may bring vitals equipment to the subject’s home to 
collect baseline assessments and leave the equipment with the subject for use during follow up 
visits at Days 12, 40, and/or recurrence. The ‘physical exam and vital signs’ and ‘signs and 
symptoms of CDI’ assessments must be performed via synchronous sponsor approved video 


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conferencing with the Investigator. It is imperative for any visit completed by home healthcare 
vendor or site staff that the physical exam and vitals be the first study procedures completed, 
once consent/assent has been collected, so the subject may be sent to an acute care clinic should 
they require immediate care. 
Blood and urine samples should be collected by the home healthcare vendor or site staff at the 
subject’s home at the baseline visit if the visit is conducted remotely. 
Following Investigator assessment of eligibility and randomization, IMP may be shipped directly 
to the subject’s home, delivered by courier, or delivered by a home healthcare vendor or site 
staff. 
Day 5 visit 
The Day 5 visit is preferably an in-clinic visit. However, if a subject is unable to complete the 
visit in-clinic for safety reasons, a sponsor-contracted home healthcare vendor or properly 
trained and delegated site staff can conduct assessments and collect samples at the subject’s 
home. 
Day 10 visit 
The Day 10 visit may be conducted in-clinic or by telephone. If conducted by telephone, stool 
sample drop off or collection of the sample from the subject’s home must be arranged. 
Used IMP wallets and any unused medication should be returned to the site during a visit, or 
couriered to site as soon as study treatment has been completed. 
Day 12, Day 40 and recurrence visit 
Day 12, Day 40, and/or any recurrence visit(s) are preferably in-clinic visits, however, may be 
completed remotely. If so, the following approaches may be taken: 
• if the subject has been provided with vital sign equipment by the site, the visit may be 
conducted with only a video conference between the Investigator and the subject in the 
presence of a guardian, including a focused physical exam and vital signs by the subject 
themself with the help of a guardian or 
• a sponsor-contracted home healthcare vendor or properly trained and delegated site staff 
may conduct the visit at the subject’s home with a guardian present and with the 
Investigator joining by video conference. 
If Day 12 and/or Day 40 visits are completed at home over video conference without the 
presence of site staff or a home healthcare vendor, the site will need to arrange for an 
appropriately qualified person to collect the blood (hematology and clinical chemistry) and urine 
samples. 
If utilizing a home healthcare vendor or site staff for remote Day 12 and/or Day 40 visits, they 
may complete the blood (hematology and clinical chemistry) and urine collections. 
If Day 12, Day 40 or Recurrence visits are completed at home stool sample drop off or collection 
of the sample from the subject’s home must be arranged. 


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4.2. 
End of Study Definition 
A subject is considered to have completed the study if he/she has attended the following visit: 
• Day 40 visit: if not cured at AOC or if cured at AOC but experiences CDI recurrence prior 
to Day 40 
• Recurrence visit: if the subject has SCR to Day 40 but has a confirmed recurrence between 
Day 40 and Day 100. 
• Day 100 visit: if the subject is cured at AOC and has no recurrence of CDI up to Day 100 
The end of the study is defined as the date of the last study assessment of the last subject in the 
study. 


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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
At screening, subjects are eligible to be included in the study only if all the following criteria 
apply. 
Legal 
1. Has signed informed consent by parents or legally authorized representatives and assent 
by the child according to local requirements (e.g., Protected Health Information [PHI]) 
prior to initiation of any study-mandated procedure. 
2. Is aged 12 to <18 years. 
Disease Characteristics 
3. Has signs and symptoms of CDI including diarrhea such that in the Investigator’s opinion 
CDI antimicrobial therapy is required. Diarrhea is defined as a change in bowel habits, 
with ≥3 UBMs (5, 6 or 7 on the Bristol Stool Chart, see Appendix 5) in the 24 h prior to 
randomization. 
4. Has tested positive for toxin A and/or B of C. difficile in the stool determined by a positive 
free toxin test (using a Sponsor agreed test).  
Contraception 
5. Has contraceptive measures in place as follows (see Appendix 4 for details): 
Male subject: 
• Agrees to use a highly effective contraceptive method as detailed in Appendix 4 
of this protocol during the treatment period and for at least 30 days after the last 
dose of study treatment 
OR 
• Agrees to adhere to abstinence 
• Refrains from donating sperm during the treatment period and for at least 30 days 
after the last dose of study treatment 
Female subject: 
• Is not pregnant or breastfeeding and must have a documented negative 
pregnancy test at screening 
• Complies with one of the following three conditions: 
i. 
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
ii. 
A WOCBP who agrees to follow the guidance in Appendix 4 on highly 
effective contraceptive methods during the treatment period and for at least 
30 days after the last dose of study treatment. 


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iii. 
A WOCBP adhering to abstinence. 
5.2. 
Exclusion Criteria 
At screening, subjects are excluded from the study if any of the following criteria apply. 
Treatments for CDI confounding with the study treatment 
1. Has received treatments for CDI confounding with the study treatment as follows: 
• Has had more than the equivalent of 48 hours of dosing of antimicrobial treatment 
active against the current episode of CDI prior to randomization or  
• Has received ridinilazole or an investigational vaccine against C. difficile any time 
in the past; anti-toxin antibodies including bezlotoxumab within the past 
6 months; or any other investigational medicinal product for treatment of CDI, or 
fecal microbiota replacement therapy within the past 3 months 
Conditions confounding with the assessments of CDI 
2. Has a clinically relevant positive stool test for pathogens other than C. difficile, within 
48 hours of randomization. Routine stool cultures and examinations for other pathogens 
are not required by the protocol unless they are suspected by the investigator and 
performed as part of standard of care.  
3. Has life-threatening or fulminant CDI with evidence of hypotension, septic shock, 
peritoneal signs or absence of bowel sounds, toxic megacolon, or ileus. 
4. Has had major GI surgery (e.g., significant bowel resection or pancreatectomy, but not 
including appendectomy or cholecystectomy) within the past 3 months or has the 
presence of a colostomy or ileostomy or has the likely requirement of an ostomy during 
the study 
5. Is receiving treatment that generally is associated with severe diarrhea, intractable 
vomiting, severe nausea, or inability to swallow that cannot be managed with antiemetics 
or antidiarrheals and that limits the ability to take oral medications. Cancer treatment that 
does not compromise ability to take study medication or cause severe diarrhea is allowed. 
Conditions confounding with the safety assessments 
6. Has been involved in a clinical trial and received an investigational medicinal product for 
an indication other than CDI within the past month or five half-lives (whichever is longer). 
Compliance with the study protocol 
7. Is unable to tolerate oral medications 
8. Has a known history of hypersensitivity or allergic reaction to vancomycin or any excipient 
of vancomycin or ridinilazole. 


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9. Is, in the Investigator’s judgment, inappropriate for participation in the study including for 
example those subjects 
a. with any other (medical) condition that would make the subject unsuitable for 
inclusion in the study 
b. who are not likely to complete the whole study for whatever reason, e.g., a short life 
expectancy 
c. who are unwilling or unable to comply with protocol requirements, for example 
complete the full course of study treatment, attend study clinic visits, provide stool 
samples, ingest capsules, tolerate blood draws 
5.2.1. 
Subject Suitability 
Subjects may participate in the study provided they are expected to be able to take oral study 
medication for 10 days and complete study assessments. 
Examples of subjects who may need to be excluded include those suffering from vomiting and/or 
severe nausea that cannot be managed with antiemetics and is limiting the ability to take oral 
medication, intubated subjects, subjects likely to require antibiotics that have activity against 
C. difficile especially in the first 40 days. Investigators are encouraged to contact the medical 
monitor to discuss individual cases as required. 
5.3. 
Lifestyle Considerations 
There are no lifestyle restrictions applicable through the study. 
5.3.1. 
Meals and Dietary Restriction 
No meal or dietary restrictions. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
No caffeine, alcohol, or tobacco restrictions. 
5.3.3. 
Activity 
No activity restrictions. 
5.4. 
Screen Failures 
Screen failures are defined as subjects who assent to participate in any of the clinical study 
assessments but are not subsequently randomized into the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure subjects to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to respond 
to queries from regulatory authorities. Minimal information includes demography, screen failure 
reasons and any serious adverse event (SAE). 
It is possible for subjects to be rescreened once for this study. If a subject is rescreened a new 
subject number will be assigned. 


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6. 
STUDY TREATMENT 
Subjects will be randomized to receive a 10-day course of ridinilazole tablets (200 mg, bid), or 
vancomycin (125 mg, qid) capsules. Blinding will be maintained by also orally administering 
matching placebo tablets/capsules. Study treatment will be provided in a blister wallet labelled per 
country requirements. Each wallet will have a unique identifier which will be used to allocate 
double-blind study treatment to each subject via the Interactive Response Technology (IRT) 
system. Study treatment wallets may be labelled as Summit Therapeutics, Inc., or Summit (Oxford) 
Limited as the listed sponsor. 
6.1. 
Administration of the Study Treatment 
Each wallet will contain all doses required for the total treatment period (i.e., 40 doses over 
10 days; 4 doses a day). Doses will be clearly labeled 1 to 40 on the wallets. It is important the 
subject takes each dose in number order starting with 1 and finishing with 40. If you miss a dose, 
then take the missed dose before or with the next dose. No more than 2 doses should be taken at 
any one time. For example, if you miss Dose 3, take Dose 3 before or with Dose 4. 
Do not crush or break the tablets or open the capsules (e.g., to pass through a feeding tube). 
Table 1: 
Dosing schedule per 24 hours (four doses) 
 
Dose 1 
Dose 2 
Dose 3 
Dose 4 
Ridinilazole Arm 
Ridinilazole 200mg 
& Vancomycin 
Dummy Placebo 
Vancomycin 
Dummy Placebo 
Ridinilazole 200mg 
& Vancomycin 
Dummy Placebo 
Vancomycin 
Dummy Placebo 
Vancomycin Arm 
Ridinilazole Dummy 
Placebo & 
Vancomycin 125mg 
Vancomycin 
125mg 
Ridinilazole 
Dummy Placebo & 
Vancomycin 
125mg 
Vancomycin 
125mg 
6.2. 
Preparation, Handling, Storage and Accountability 
The Investigator or designee must confirm appropriate temperature conditions (below 25°C/77°F 
and not refrigerated or frozen) have been maintained during transit for all study treatment received 
and any product complaints or discrepancies are reported and resolved before use of the study 
treatment. 
Only subjects randomized in the study may receive study treatment and only authorized site staff 
may supply or administer study treatment (as documented by the Investigator on the Delegation of 
Authority log). All study treatment must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions with 
access limited to the Investigator and authorized site staff. 
Any product complaints or storage temperature excursions identified during storage of 
investigational product should be reported to the Sponsor and resolved prior to use. 


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The Investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study treatment accountability, reconciliation, and record maintenance (i.e., receipt, 
reconciliation, and final disposition records). 
The Investigator or Pharmacist should arrange for destruction of any unused IMP following full 
reconciliation of IMP and Sponsor (or delegate) approval. Destruction will be conducted locally 
where possible using a method in line with Sponsor provided requirements. Destruction should be 
conducted per the sites standard operating procedure (SOP) and a destruction certificate, including 
method of destruction, should be issued. IMP may be returned to the Sponsor if local destruction 
is not possible. 
Further guidance and information for the final disposition of unused study treatments are provided 
in the Investigator Trial Site File. 
Study treatment wallets may be labelled as Summit Therapeutics, Inc., or Summit (Oxford) 
Limited as the listed sponsor. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Randomization will occur on Day 1 after subject eligibility for the study has been confirmed. 
Subjects will be randomized to one of two treatment groups in a 3:1 ratio to either the ridinilazole 
arm or the vancomycin arm. 
The Investigator or designee will use the IRT system to randomize a subject. A computer- 
generated central randomization will be used which will be stratified by current comorbidities 
(see Section 4.1). Once a randomization number has been assigned it will not be re-assigned. 
Study treatment will be dispensed at the randomization visit (Day 1). Returned study treatment 
should not be re-dispensed to other subjects. 
This is a double-blind study. To maintain the blind, a double-dummy approach for study treatment 
blinding will be employed. Vancomycin will be encapsulated within a Size 0 Swedish Orange, 
hard gelatin, and immediate release capsule. There will be a matching vancomycin placebo. 
Ridinilazole is presented as a coated tablet. There will be a matching ridinilazole placebo. 
Subjects randomized to ridinilazole will receive active ridinilazole, and vancomycin placebo to 
achieve dosing with ridinilazole bid. Subjects randomized to vancomycin will receive active 
vancomycin and ridinilazole placebo to achieve dosing with vancomycin qid. The study drug and 
packaging will be manufactured in such a way that subjects and study site staff will not know to 
which arm a subject has been assigned. 
The adverse event profile of vancomycin and ridinilazole indicates that most 
adverse events can be managed without unblinding. If the Investigator believes 
unblinding is necessary to manage a subject, then emergency unblinding may be 
conducted via the IRT system but should only be performed when knowledge of 
the treatment is essential for medical decisions and/or further emergency 
management of the subject. 
In case of an emergency, the Investigator (when possible) is responsible for 
determining if unblinding is warranted. Subject safety must always be the first 
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If unblinding is determined to be warranted, the Investigator should make every 
effort to contact the Medical Monitor prior to unblinding unless this could delay 
emergency treatment of the subject. 
If unblinding occurs, the Sponsor must be notified within 24 hours. The sponsor 
should remain blind to the treatment assignment. The date and reason that the 
blind was broken must be recorded in the source documentation. 
6.4. 
Study Treatment Compliance 
In accordance with ICH-GCP, each study center will account for all supplies of blinded medication 
(study treatment). Details of receipt, storage, assembly, and return will be recorded. The unit of 
accountability will be one capsule or one tablet. 
Compliance with the study treatment is critical to the integrity of the study 
objectives. 
To help ensure compliance the Investigator will discuss the following with the 
subject and the subject’s guardian(s) on Day 1 and on Day 5: 
the importance of administering study treatment (medication; all tablets and 
capsules) per protocol and to remind the subject to continue to complete all 
doses regardless of resolution of symptoms. 
The subject’s guardian or subject will be required to return all empty packaging and unused study 
treatment (wallet, capsules, tablets) to the Investigator at the Day 12 (AOC) visit so that a final 
compliance check can be conducted. 
During the treatment period, the subject is requested to fill out the Study Drug Administration 
form daily indicating at which time points the study medication has been taken. A guardian can 
help filling out this form (that will be provided by the site). 
In the event of overdose see Section 8.4. 
6.5. 
Concomitant Therapy 
Concomitant therapy is any medication, vaccine, procedure or therapy (including over the counter 
or prescription medicines, vitamins, and/or herbal supplements) that the subject is receiving at the 
time of enrollment or receives during the study. 
All concomitant therapies should be recorded from 4 weeks prior to randomization and throughout 
the subject’s duration in the study (i.e., until end of study; see Section 6.5.1). The reason for use, 
the dates of administration and the dosing information should be recorded in the eCRF. 
6.5.1. 
Potential Confounding Medications 
Refer to Table 2 for a list of medications that may impact CDI status or assessment of adverse 
events and hence have the potential to confound study results. Control over administration of 
these medications is necessary, considering the safety and efficacy endpoints of the study, but it 
is understood that a medication should not be withheld for purposes of the study if an alternative 


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and comparable treatment cannot be provided, and the subject’s health would otherwise be 
compromised. Confounding medications include but are not limited to these listed in the 
following tables.  
Potentially Confounding Medications 
Medications that could potentially confound data analysis should be avoided, 
if possible, without compromising the care for the subject. 
If antimicrobial therapy is required for infections other than those due to C. 
difficile, antimicrobials without activity/efficacy against C. difficile should be 
prescribed if possible 
Investigators should contact the medical monitor for any questions regarding concomitant 
or prior therapy. 
During the study, both during the treatment period and during the follow up period, 
subjects who take any confounding medications should not necessarily be discontinued 
from study treatment and should not be withdrawn from the study. 
Table 2: 
Potentially Confounding Medications Which May Not Be Permitted During 
Study Treatment (Day 1 to Day 12 and/or during Follow-up (Day 12 to 
Day 100) 
Drug Class 
From Randomization to Day 
12/AOC 
During Follow Up 
CDI Treatments 
Antimicrobial treatments for 
CDI (including but not limited 
to oral vancomycin, IV or oral 
metronidazole, fidaxomicin) 
None permitted 
For recurrence, as per standard 
clinical practice 
Anti-toxin antibodies including 
bezlotoxumab 
None permitted 
For recurrence, as per standard 
clinical practice 
Antimicrobial treatments that 
may be effective at treating CDI 
(including but not limited to oral 
rifamycins, tigecycline, 
nitazoxanide, bacitracin, fusidic 
acid, oral teicoplanin) 
None permitted unless used for 
conditions other than CDI 
Prescribe alternative 
antimicrobial if use is for 
conditions other than CDI where 
possible. 
Prescribed probiotics, prebiotics 
and herbal products or non-
prescribed intended to treat CDI 
None permitted unless patient 
was taking the treatment prior to 
enrolment 
For recurrence, as per standard 
clinical practice 
Intravenous immunoglobulin 
(IVIG) 
None permitted unless patient 
was receiving regular IVIG 
treatment prior to enrolment  
For recurrence, as per standard 
clinical practice 


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Drug Class 
From Randomization to Day 
12/AOC 
During Follow Up 
CDI Treatments 
Fecal microbiota replacement 
None permitted 
For recurrence, as per standard 
clinical practice 
IMP for CDI 
None permitted 
None permitted 
Investigational vaccine against 
C. difficile 
None permitted 
None permitted 
Non-CDI Treatments 
Other antimicrobials not active 
against C. difficile1 
Permitted 
Permitted 
Anti-diarrheals, anti- 
peristaltics, laxatives 
Permitted 
For recurrence, as per standard 
clinical practice. 
IMP for other indications 
None permitted 
None permitted 
1 May contribute to recurrence. Important to document in the eCRF throughout the study. 
 
During the study, both during the treatment period and during the follow up period, subjects who 
take any confounding medications should not necessarily be discontinued from study treatment 
and should not be withdrawn from the study. 
Investigators should contact the medical monitor for any questions regarding concomitant or prior 
therapy. 
6.6. 
Dose Modification 
Not applicable. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
WITHDRAWAL FROM STUDY 
7.1. 
Discontinuation of Study Treatment 
A subject will discontinue study treatment for any of the following reasons: 
• Withdrawal of consent/assent to continue taking study treatment. The reason for this will 
be documented if provided. 
• The study Investigator or Sponsor, for any reason, decides the subject should be 
discontinued from the study treatment. 
• Adverse events, classed as possibly or probably study treatment related by the Investigator, 
which cannot be tolerated by the subject 
• Pregnancy during the study treatment period. See Appendix 4 and Section 8.3 Pregnancy. 
• Death 
• Non-compliance 
• Persistent diarrhea (moved to standard of care) 
• Lost to follow-up 
• Other 
Subjects discontinued from study treatment, should continue with all study visits and assessments 
so that (safety) data can be collected. If subjects do not agree to this, then they should complete 
the early termination assessments. 
Study treatment (wallet, capsules/tablets) assigned to the discontinued subject must not be assigned 
or handed over to another subject. 
7.2. 
Withdrawal from Study 
A subject may withdrawal or be withdrawn from the study for any of the following reasons: 
• Withdrawal of consent/assent to continue study participation; the reason for this will be 
documented if provided. 
• The study Investigator or Sponsor, for any reason, decides the subject should be 
discontinued from the study 
• Adverse event(s) 
• Death 
• Lost to follow-up 
• Other 


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7.2.1. 
Withdrawal of Consent/Assent 
All subjects are encouraged to continue through to the end of the study. However, a subject may 
withdraw from the study at any time at his/her own or parental/responsible adult request or may 
be withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, 
or administrative reasons. 
If the subject withdraws consent/assent for collection of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent/assent. 
See the Schedule of Assessments for data, evaluations, and samples to be collected when a subject 
ends participation in the study. The reason for withdrawal is to be documented on the eCRF and 
in the source documentation (e.g., patient file). 
7.2.2. 
Lost to Follow Up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by staff of the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site staff must attempt to contact the subject and/or subject’s guardian and reschedule 
the missed visit as soon as possible. The subject and subject’s guardian should be 
counselled on the importance of maintaining the assigned visit schedule and the site should 
ascertain whether the subject wishes to and/or should continue in the study. 
• Before a subject is deemed lost to follow up, the Investigator or designee must make every 
effort to regain contact with the subject and/or subject’s guardian (where possible, 
3 telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods). These contact attempts should be documented in the 
subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.2). Protocol waivers or 
exemptions will not be granted by the Sponsor or delegate. Adherence to the study design 
requirements, including those specified in the SoA (Section 1.2), is essential and required for study 
conduct. 
All screening evaluations must be completed and reviewed to confirm that potential subjects meet 
all eligibility criteria. The Investigator or study team designee will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for screening 
failure, as applicable. 
Immediate safety concerns should be discussed with the Sponsor Medical Monitor or delegate 
instantaneously upon occurrence or awareness to determine if the subject should continue or 
discontinue study treatment. 
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.2). 
8.1.1. 
Medical History (Including CDI History) 
The following will be recorded prior to randomization: 
• All relevant and significant medical history diagnosed or treated within the last 12 months 
and relevant chronic conditions that have not had an exacerbation in the last 12 months 
prior to randomization 
• All medications taken up to 4 weeks prior to randomization 
• All known episodes of CDI along with the treatment administered 
• Information on the current/baseline CDI including confirmation of positive C. difficile free 
toxin, the number of UBMs in the 24 hours prior to randomization and current signs and 
symptoms of CDI. 
Relevant medical history includes events that may contribute to the outcome of a treatment for 
CDI such as: major gastrointestinal surgery, nonsurgical gastrointestinal procedures, significant 
infection, condition resulting in immunosuppression, gastrointestinal disorders/diseases, or 
cancer. 
Significant medical history includes pathology (events, diseases, disorders, or conditions) that 
may be useful in assessing a safety event occurring during the study such as: major non-
gastrointestinal surgery and major pathology of the cardiovascular, respiratory, endocrine, 
immunological (including HIV status) and neurological systems. 
8.1.2. 
Physical Examinations 
The physical exam may be conducted at either screening or baseline. If conducted at screening, 
then only the vital signs must be repeated at the baseline visit if done on a different date. A 
physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, 
gastrointestinal, and neurological systems. Height (at screening only) and weight will also be 


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measured and recorded. Investigators should pay special attention to clinical signs related to 
previous serious illnesses. 
8.1.3. 
Vital Signs 
Vital signs will be measured in a semi-supine position after 5 minutes’ rest and will include 
temperature, systolic and diastolic blood pressure, and pulse. The same arm should be used to 
measure blood pressure throughout the study for each subject, if possible. 
8.1.4. 
Electrocardiograms 
A single 12-lead ECG will be obtained at screening or baseline visit, prior to randomization using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals. Manual measurements and calculations may be conducted in the absence of automated 
reporting of such intervals. 
An ECG does not need to be performed if most recent ECG was normal (using the parameters and 
qualifications mentioned in Section 8.1.4) and was done in the 12 months prior to randomization, 
the screening/baseline ECG will be reviewed and signed by the Investigator or a medically 
qualified designee. Any abnormalities will be marked as clinically significant or not clinically 
significant. Clinically significant abnormalities will be documented as current medical history and 
reported as an SAE if the definition of serious is met. 
8.1.5. 
Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical laboratory tests that will be performed at a central 
laboratory and the SoA (Section 1.2) for the timing and frequency. However, the urine 
pregnancy test will be performed locally. 
The Investigator must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports 
must be filed with the source documents. Clinically significant abnormal laboratory findings are 
those which are not associated with the underlying disease, unless judged by the Investigator to be 
more severe than expected for the subject's condition. 
All laboratory tests (with the exception of pregnancy tests) with values considered clinically 
significantly abnormal during participation in the study or within 5 days after the last dose of study 
treatment should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or medical monitor. 
• If such values do not return to normal/baseline within a period judged reasonable by the 
Investigator, the etiology should be identified, and the Sponsor notified. 
• All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted 
in accordance with the laboratory manual and the SoA (Section 1.2). 
• If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the Investigator (e.g., SAE or AE), then the results must be 
recorded in the eCRF. 


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8.2. 
Adverse Events and Serious Adverse Events 
Refer to Appendix 3 for definitions and for details on how to assess, classify, and report adverse 
events (AEs)/ serious adverse events (SAEs). 
Adverse Events (AEs) will be reported by the subject/guardian (or, when appropriate, by a 
caregiver, surrogate, or the subject's legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study treatment or study procedures, or that 
caused the subject to discontinue the study treatment. (See Section 7) 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All Serious Adverse Events (SAEs) will be collected from the signing of the informed consent 
form (ICF) until Day 100/ the End of Study visit. 
All AEs will be collected from the time and date of first dose of study treatment until the D40 
follow-up visit. 
Changes in medical conditions that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the Medical History page of the eCRF and not the AE eCRF 
page. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours of awareness 
of the event, as indicated in Appendix 3. The Investigator will submit any updated SAE data to the 
Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must notify the Sponsor within 
24 hours of awareness. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3. 
8.2.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the subject should be used to inquire about AE occurrences. 
8.2.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.2.2). Further 
information on follow-up procedures is given in Appendix 3. 


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8.2.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal obligations 
and ethical responsibilities towards the safety of all other subjects and the safety of a study 
treatment under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical investigation. 
The Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB)/Independent 
Ethics Committees (IEC), and Investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) per local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
• An Investigator who receives an Investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate per local requirements. 
8.2.5. 
Events NOT Meeting the AE/SAE Definition:  
• Disease Related Events (refer to Section 8.2.6)  
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).  
8.2.6. 
Disease-Related Events Not Qualifying as AEs or SAEs 
Disease-related events (DREs) are associated with the disease under study and will not be 
reported according to the standard process for reporting of SAEs even though the event may 
meet the definition of an SAE. 
The following DREs are common in patients with CDI:  
• CDI recurrence 
o CDI recurrences will be recorded for the patient on the “Suspected Recurrence of 
CDI” CRF page.  
Note: If on evaluation, no recurrence is deemed to have occurred, any symptoms (or preferably 
diagnosis) reported by the patient must be reported as AEs (up to Day 40) and as SAEs (anytime 
during the study if the criteria for an SAE are met).  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with CDI. 


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• Treatment failure/lack of efficacy is not an adverse event but will be captured as an 
efficacy endpoint. 
• Signs or symptoms of CDI, including expected progression or worsening of CDI 
However, if any of the following complications related to CDI occurs, then the event must be 
recorded and reported as such as an SAE (instead of a progression or worsening of CDI): 
• Toxic megacolon 
• Fulminant colitis 
• Colonic perforation  
A medical monitor will monitor suspected recurrence events on a regular basis. 
8.3. 
Pregnancy 
• Details of all pregnancies in female subjects and, female partners of male subjects will be 
collected after the start of study treatment and until 30 days after the last dose. 
• If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.4. 
Treatment of Overdose 
There is no specific treatment for overdosing; general medical support measures are to be in 
place, if required. Any SAE or AE associated with excessive dosing must be followed as any other 
SAE or AE. These events are only considered AEs or SAEs if there are associated clinical signs 
and symptoms.  
8.5. 
Pharmacokinetics 
8.5.1. 
Plasma PK Samples 
PK plasma samples will be collected on Day 1 or Day 2 and on Day 5 or Day 6. If the last day of 
dosing with study medication occurs prior to Day 5, the sample is to be taken on the last dosing 
day. An accurate time of dosing and plasma sampling should be recorded. 
It is understood that subjects randomized to the ridinilazole arm will receive active ridinilazole in 
Dose 1, placebo in Dose 2, active ridinilazole in Dose 3, placebo in Dose 4, etc. Therefore, to 
ensure that PK is taken following an active dose of ridinilazole, the blood draws for all subjects 
will occur as follows: 
o Day 1 or 2 - at 4 hours (±1 hour) post either Dose 1, 3, 5 or 7 
o Day 5 or 6 - at 4 hours (±1 hour) post either Dose 17, 19, 21 or 23. 
The bioanalytical laboratory will be unblinded and all samples from the ridinilazole-treated 
subjects will be analyzed. Appropriate measures will be taken to ensure that the laboratory does 


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not disclose unblinded information to the study sites or Sponsor/CRO/Vendor team. Transfer of 
PK data will not be conducted until after the study is unblinded. 
Residual plasma samples may be retained for up to 5 years from the end of the study for exploratory 
analyses of circulating ridinilazole metabolites, biomarkers and/or assessing vancomycin 
concentrations. If performed, this work will be reported separately. 
8.5.2. 
Fecal PK Samples 
Fecal samples to determine ridinilazole concentrations in the stool will be collected on Day1 (after 
dosing) or Day 2 and on Day 5 or Day 6. If the last day of dosing with study medication occurs 
prior to Day 5, the sample is to be taken on the last dosing day. 
As for plasma PK samples, the bioanalytical laboratory will be unblinded and all samples from the 
ridinilazole-treated subjects will be analyzed. Appropriate measures will be taken to ensure that 
the laboratory does not disclose unblinded information to the study sites or Sponsor/CRO/ 
Vendor team. Transfer of PK data will not be conducted until after the study is unblinded. 
8.6. 
Efficacy Assessments 
8.6.1. 
Assessment of Cure/Sustained Clinical Response 
Efficacy endpoints are secondary endpoints and will be assessed at the times outlined in the SoA 
(Section 1.2). 
The Investigator will assess whether a subject was a clinical cure or failure at Day 12 (AOC) and 
whether a subject has a recurrence. Sustained clinical response (SCR) at 30 days post End-of- 
Treatment (EOT) is defined as clinical cure at the AOC visit and no recurrence of CDI at Day 
40. Those subjects cured at AOC and with a SCR at Day 40 will continue to be followed until 
Day 100 or recurrence of CDI (whichever comes earlier). SCR at 60- or 90-days post EOT are 
defined as cure at the AOC visit and no recurrence of CDI at Day 70 or Day 100 respectively. 
Clinical response will be assessed at the AOC visit. SCR based on clinical response, defined as 
clinical response with no recurrence assessed through 30 days post-EOT will be assessed through 
30 days post-EOT. 
The following definitions will be used: 
Clinical cure 
The investigator assessment of clinical cure at the AOC visit is defined by the following: 
The resolution of diarrhea (< 3 unformed stools in a 1-day period) while on treatment, that is 
maintained until the AOC (EOT +2 days) visit, and no further requirement for further CDI 
antimicrobial therapy is needed through EOT + 2 days. 
Recurrence 
Recurrence is defined as a new episode of diarrhea and other signs and symptoms of C. difficile 
with a positive C. difficile free toxin test that requires CDI treatment. 


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Clinical response 
Clinical response is defined as:  
• less than 3 UBMs for 2 consecutive days and maintained through the EOT without further 
CDI antimicrobial treatment at EOT+2 days or  
• the investigator’s assessment that the subject no longer needs specific CDI antimicrobial 
treatment after completion of the course of study medication. 
Subjects/guardians will be encouraged to contact the site if diarrhea occurs. The Investigator or 
site staff indicated on the site delegation log will contact the subject/guardian weekly to enquire 
about any episodes of diarrhea until Day 40 and thereafter on Day 70 and Day 100. 
The Investigator will request the subject be assessed for recurrence of CDI if a new episode of 
diarrhea is reported, unless the Investigator is highly confident that the diarrhea is due to a cause 
other than C. difficile. Where possible the assessment, including a free toxin test, should occur as 
soon as possible, and within 48 hours of the report. 
8.6.2. 
Weekly Unformed Bowel Movement Contact 
Weekly telephone contact will be made with subjects until Day 40, and thereafter on Day 70 and 
Day 100. Subject will be asked if CDI recurrence is suspected if 3 or more UBMs have occurred 
within a 24-hour period since last contact. 
8.6.3. 
Daily Unformed Bowel Movement Contact 
Daily telephone contact will be made with subjects on the following days: EOT -2, EOT -1, 
EOT, EOT +1, EOT +2. Subject will be asked if 3 or more UBMs have occurred within a 1-day 
period. Alternatively, may occur in person. 
8.6.4. 
Signs and Symptoms of CDI 
The Investigator should record the subject’s current signs and symptoms of CDI at baseline/ 
Day 1, Day 10 and at Day 12/EOT +2 days. Signs and symptoms will also be recorded during an 
assessment of suspected recurrence. The Investigator should ask the subject for signs and 
symptoms that have occurred over the 1-day period prior to the assessment of suspected 
recurrence. 
Record all symptoms (loose stools, abdominal cramps or pain, fever, visible blood or pus in stool, 
nausea, vomiting, loss of appetite or other) that apply to the subject at that evaluation on the eCRF 
at the visits indicated. 
8.6.5. 
Suspected Recurrence 
If there are signs and symptoms that could relate to CDI (e.g., diarrhea), that situation is referred 
to as a ‘suspected recurrence’. 
It is required that every new episode of diarrhea considered a ‘suspected recurrence’ is investigated 
via a free toxin test unless the Investigator is highly confident that the diarrhea is due to a cause 
other than C. difficile. 


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• If the signs and symptoms (e.g., diarrhea) are not considered a ‘suspected recurrence’: 
record the reason in the eCRF on the ‘Suspected Recurrence of CDI’ eCRF page. 
• If the signs and symptoms (e.g., diarrhea) are considered a ‘suspected recurrence’: 
o Conduct a local free toxin test (FTT) as soon as possible and no later than 48 hours 
after identifying a suspected recurrence. If the test is invalid it should be repeated. 
If the FTT test is negative it can be repeated once on the same sample or fresh 
sample. 
o Refer to the free toxin test result to determine whether CDI treatment is required. 
o Complete the “Suspected Recurrence of CDI” eCRF page 
Since C. difficile free toxin EIA kits (i.e., the FTT) can have sub-optimal sensitivity, in all instances 
of suspected recurrence of CDI that are associated with a negative free toxin test (FTT) result 
(obtained locally by the site), a stool sample should be collected for testing by Cell Cytotoxicity 
Neutralization Assay (CCNA) at a specialized central laboratory. The sample should be frozen 
within 24 h of production and stored to shipment to the Central Laboratory (as for all other 
samples). Alternatively, an aliquot of the original sample used to perform the FTT can be 
prepared for the CCNA if not older than 24 h of production. This requirement to prepare an 
aliquot for CCNA testing at a specialized central laboratory in case of a negative FTT at 
suspected recurrence is irrespective of any locally conducted CCNA. 
Recurrence of CDI per protocol is defined as a new episode of signs and symptoms of C. difficile 
with a positive C. difficile free toxin test that requires CDI treatment. A confirmed recurrence of 
CDI is considered a disease-related event (DRE) and not an adverse event (AE or SAE; see 
Section 8.2). 
If on evaluation, no recurrence is deemed to have occurred, any symptoms (or preferably 
diagnosis) reported by the patient must be reported as AEs (up to Day 40) and as SAEs (anytime 
during the study if the criteria for an SAE are met); see also Section 8.2 and Section 10.3. 
8.6.5.1. 
Recurrence Visit 
Investigators are requested, subject to local treatment guidelines and Investigator judgement, to 
await the results of the local free toxin test (i.e., the FTT and not the CCNA assay) prior to initiating 
antimicrobial treatment for a suspected recurrence. The Investigator may discuss with the Medical 
Monitor if required. 
At the scheduled visits indicated in the SoA (Section 1.2), the Investigator should also assess 
whether the subject has met the criteria for recurrence. In case of a ‘suspected recurrence’ all the 
assessments as indicated in the SoA Recurrence Visit (Section 1.2) should be carried out. 
Investigators are urged to follow the subject closely and directly assess and provide medical 
management of each suspected recurrence throughout the study. If a subject is assessed and/or 
treated by a non-study health care professional, the Investigator should obtain as much information 
as possible for eCRF entry. 


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To ensure the data integrity of the efficacy endpoints, it is critical that the 
following requirements are met for all subjects where possible: 
• A free toxin test is conducted as soon as possible following suspicion of 
recurrence. 
• Refer to the results of the free toxin test to determine if CDI treatment is 
required. 
• Any potentially confounding medications initiated must be recorded in 
the eCRF 
For all suspected recurrences associated with a negative free toxin test result 
obtained locally by the site, a stool sample should be collected for testing by 
CCNA at a specialized central laboratory. 
8.7. 
Stool (Feces) Collection for Future Research 
Subjects will be required to provide a stool sample at the time points specified in the SoA 
(Section 1.2). Subjects will be provided with a home collection kit. If a sample is requested by 
the Investigator, the subject will provide the sample to the study site within 24 hours of producing 
the sample. 
Samples will be immediately tested with a free toxin test, in the event of a suspected recurrence. 
Aliquots of the sample for future research will be prepared and frozen within 24 h of production 
and stored for shipment to the Central Laboratory. Guidance and instructions for Investigators will 
be available in the lab manual. 
Stool samples will be stored for up to 5 years for potential microbiology, microbiome and/or 
metabolome analysis. 
A stool sample produced and frozen within 24 hours is required. If the sample used 
for CDI testing was produced >24 hours, a fresh sample should be provided where 
possible. 
8.8. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.9. 
Genetics 
Genetics are not evaluated in this study. 
8.10. 
Biomarkers 
Biomarkers are not evaluated in this study. 


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8.11. 
HEOR, Medical Resource Utilization 
Medical resource utilization and health economics data, associated with medical encounters, will 
be collected in the eCRF by the Investigator and study-site personnel for all subjects throughout 
the study. Protocol-mandated procedures, tests, and encounters are excluded. Data collected will 
include (but will not be limited to): 
• Length of hospital stay 
• Hospital admission and readmission rates and reasons for admission 
• Subject location at admission and subject’s discharge location 
• Other location of healthcare access that didn’t result in hospitalization, i.e., urgent care 
facility, doctor visit, telemedicine 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Sample Size Determination 
The sample size has not been chosen on the basis of a formal hypothesis test. However, 
40 subjects (with a 3:1 allocation) are considered sufficient to investigate the safety of ridinilazole 
compared to vancomycin and 30 ridinilazole subjects are considered sufficient to assess the 
pharmacokinetics of ridinilazole in this subject population. 
9.2. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Screened 
All subjects who sign the ICF 
Randomized 
All subjects randomly assigned to study treatment. 
Safety 
All subjects randomly assigned to study treatment and who take at least 1 dose of 
study treatment. Subjects will be analyzed according to the treatment they received. 
Pharmacokinetic [PK] 
All subjects who are treated with ridinilazole and have at least one measured 
concentration of ridinilazole (including values less than the lower limit of 
quantification). 
Modified ITT [mITT] 
(Efficacy) 
All subjects in the ITT population who have a diagnosis of CDI confirmed by the 
presence of free toxin in stool and have ≥3 UBMs in the 24 hours prior to 
randomization. 
9.3. 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before unblinding and database 
lock and will describe the subject populations to be included in the analyses, and procedures for 
accounting for missing data. This section is a summary of the planned statistical analyses of the 
primary and secondary endpoints. 
Any deviations from the planned analyses post database lock will be described and justified in the 
final clinical study report. 
9.3.1. 
Safety Analyses 
All safety evaluation will be performed on the safety population. 
Treatment-emergent adverse events, i.e., any adverse events emerging after the first dose of study 
medication, will be summarized by treatment group and by System Organ Class and Preferred 
Term, in accordance with the MedDRA coding dictionary. The number of subjects reporting each 
AE preferred term will be tabulated for all TEAEs and separately for those considered as related 
to study treatment by the Investigator.  
Changes from baseline in laboratory parameters and vital signs will be summarized by treatment 
group and visit. Baseline will be taken as the last measurement prior to dosing. 


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9.3.2. 
Pharmacokinetic Analyses 
Summary statistics will be reported for ridinilazole plasma and fecal concentrations by time point 
for the PK population. A count of the number of samples below the level of quantification (BLQ) 
will be provided for each time point. 
9.3.3. 
Efficacy Analyses 
All efficacy analyses will be performed on the mITT population. 
The proportion of subjects with SCR at 30 days post EOT will be presented for each treatment 
group, along with its 95% 2-sided binomial confidence intervals. A similar summary will be 
produced for the proportions of subjects with clinical cure at AOC, SCR at 60 days post EOT and 
SCR at 90 days post EOT. 
Details of any exploratory analyses will be documented in the SAP that will be finalized before 
database lock. 
9.4. 
Interim Analyses 
The Sponsor and Delegate medical monitors will review the safety data periodically during the 
study. 
An independent Data and Safety Monitoring Board (DSMB) will review unblinded safety data 
on a regular basis during the course of the study, as defined in the DSMB Charter. Following 
each review, the DSMB will recommend action regarding the study (continue; continue with 
changes; temporarily stop; or stop). The specifics regarding the DSMB organization and 
procedures will be outlined in the DSMB Charter. 
There is no plan to conduct a formal interim analysis. However, the sponsor may request an 
interim analysis to support the regulatory submission of ridinilazole if, at the time of filing for 
adults, this study is still ongoing. The results of this interim analysis will not be used to modify or 
terminate the study; therefore, no formal stopping rules will be applied. The interim analysis will 
include all subjects who have completed the study at the time of the data-cut date. All data will be 
cleaned and verified prior to reporting. Any changes to the data previously reported will be fully 
auditable and discussed in the final report. 
The sponsor recognizes that by performing this interim analysis the study will be unblinded for 
the reported subjects at the interim and this may introduce bias with the ongoing study. To 
minimize this bias investigators and site staff will remain blinded, so the impact on the ongoing 
care and recruitment of subjects is limited. In addition, any changes in the reporting of the data 
after unblinding will be clearly documented in the final clinical study report. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o Applicable ICH Good Clinical Practice (GCP) Guidelines 
o Applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to study 
subjects. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the study and 
for 1 year after completion of the study. 
10.1.3. 
Informed Consent/Assent Process 
Written or electronic informed consent and/or assent must be obtained from each subject (and their 
parents/guardian) prior to participation in the study. Written informed consent and/or assent will 
be collected following a review of the subject’s information leaflet by the potential subject and 


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their parents/guardian and a discussion between the subject and their parents/guardian and the 
Investigator or suitably qualified designee. 
The Investigator or his/her representative will explain the nature of the study to the subject and/or 
his/her legally authorized representative and answer all questions regarding the study. 
Subjects must be informed that their participation is voluntary and that they are free to refuse to 
participate and may withdraw their consent/assent at any time and for any reason during the study 
period. 
Subjects or their legally authorized representative (if applicable) will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent/assent was obtained 
before the subject was randomized in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent/assent must also sign the ICF. Subjects 
who are rescreened are required to sign a new ICF. A copy of the ICF(s)/must be provided to the 
subject or the subject’s legally authorized representative. Subjects who are rescreened are 
required to sign a new assent. 
For electronic Consent (eConsent), the informed consent process should be captured electronically 
via eConsent platform with an impartial witness, however, subjects may sign a paper 
consent/assent form when the screening visit is done in-clinic. If the visit must be done remotely 
and the subject cannot adhere to eConsenting, they may have the consent/assent form(s) emailed 
to them and carry out a synchronous consent/assent discussion over the phone. Consent form(s) 
must be received and acknowledged by the site prior to the commencement of any study 
procedures. Original, signed consent/assent form(s) must be returned to the site either at the next 
in-clinic visit, posted to the site, or returned via courier or any other approved alternate method. 
Sites may provide an initial assent form for the free toxin test before requesting the subject’s assent 
for the full study (subject to requirement and local regulations). Consent for a toxin test conducted 
per standard of care is not required. 
A separate signature will be required to document a subject's agreement to allow any remaining 
specimens to be stored for up to 5 years to be used for exploratory research. Subjects who decline 
to participate in this optional research will not provide this separate signature. 
10.1.4. 
Data Protection 
To ensure the privacy and safety of children, the sponsor will not knowingly collect data on 
children without the consent of the parent or guardian. 
Where possible, the processing of the personal data of participants will be minimized by making 
use of a unique participant study number only on study documents and electronic database(s). 
Any subject records or datasets that are transferred to the Sponsor will contain the identifier 
only; subject names or information which would make the subject directly identifiable will not 
be transferred. 
All documents will be stored securely and only accessible by study staff and authorized personnel. 
The study staff will safeguard the privacy of participants’ personal data. 


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The subject will be informed how his/her personal study-related data will be used by the Sponsor 
in accordance with relevant data protection law. The subject will be informed that his/her medical 
records may be examined by Clinical Quality Assurance auditors or other authorized personnel 
appointed by the Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.5. 
Dissemination of Clinical Study Data 
The study will be posted on ClinicalTrials.gov in the United States and posted on other equivalent 
global registries as required. The results from this trial will be uploaded to the various registries 
when appropriate to do so and in line with the requirements of the individual registries. 
Summit will provide the Clinical Study Report to regulatory authorities as required. The 
Investigator will be provided with the full summary of the study results. 
10.1.6. 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic eCRF unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. The Investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF. 
Source data should be attributable, legible, contemporaneous, original, accurate, and complete. 
Changes to source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (e.g., via an audit trail). The Investigator must permit study-related 
monitoring, audits, IRB/IEC review, and regulatory agency inspections and provide direct access 
to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of subjects are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
10.1.7. 
Source Documents 
Describe procedures for the identification of data to be recorded directly on the eCRF considered 
as source data. Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical records 


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must be available. Definition of what constitutes source data can be found in the Investigator Trial 
Site File. 
10.1.8. 
Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are not 
limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the Investigator 
• Discontinuation of further study treatment development 
10.1.9. 
Publication Policy 
Summit fulfills its commitment to publicly disclose complete clinical trial results, regardless of 
outcome, through posting the results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the 
European Clinical Trials Database (EudraCT), and/or http://www.summitplc.comand other 
public registries in accordance with applicable local laws/regulations. Additionally, the results 
from this study may be presented in a peer-reviewed journal or at scientific meetings after 
finalization of the clinical study report. As this is a multi-center trial, the primary manuscript will 
contain the complete results across all sites; authorship will be determined by mutual agreement. 
All publications relating to this study will comply with recognized ethical standards concerning 
publications and authorship, including Section II - “Ethical Considerations in the Conduct and 
Reporting of Research” of the Uniform Requirements for Manuscripts Submitted to Biomedical 
Journals, http://www.icmje.org/index.html#authorship, established by the International 
Committee of Medical Journal Editors. 
After publication of the primary manuscript, principal investigators may publish results based on 
the information collected and data generated at their site, regardless of study outcome. This 
secondary manuscript must reference the primary manuscript. The principal investigator will 
submit their draft publication to Summit for review at least 30 days prior to submission to a journal 
for review of potentially confidential material and/or intellectual property. 
Summit is committed to sharing key data, relevant to their ongoing care, with subjects who 
participate in their clinical trials. After publication of the primary manuscript, subjects may request 
their individual data from their investigator. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 3 will be performed by a Central Laboratory except for the 
pregnancy test. 
• Additional tests may be performed at any time during the study as determined necessary 
by the Investigator or required by local regulations. 
Table 3: 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: MCV 
MCH 
%Reticulocytes 
White blood cell (WBC) 
count with Differential: 
Neutrophils Lymphocytes 
Monocytes Eosinophils 
Basophils 
Red blood cell (RBC) Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
Blood urea 
nitrogen 
(BUN) 
Potassium 
Aspartate Aminotransferase 
(AST)/ Serum Glutamic- 
Oxaloacetic Transaminase (SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
Alanine Aminotransferase 
(ALT)/ Serum Glutamic- Pyruvic 
Transaminase (SGPT) 
Total Protein 
Glucose [non- 
fasting] 
Calcium 
Alkaline phosphatase 
Albumin 
Other Tests 
Urine human chorionic gonadotropin (hCG) pregnancy test (as needed for women of 
childbearing potential)2 
The PK, CCNA, microbiology, microbiome & metabolome analysis will be performed by 
specialist centralized laboratories. 
NOTES: 
1 All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT 
≥3 × ULN and international normalized ratio (INR) >1.5, if INR measured which may indicate severe liver 
injury (possible Hy’s Law). These liver chemistries or the diagnosis explaining them must be reported as an 
SAE  
2 Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. If serum testing is required, it may be conducted via the local or central laboratory whichever is most 
convenient. 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded. 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
AE Definition 
• An AE is any untoward medical occurrence in a subject or clinical study subject, 
temporally associated with the use of study treatment, whether or not considered 
related to the study treatment. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study treatment. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
Results in death 
Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the subject 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that 
occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred, or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 


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Is a congenital anomaly/birth defect 
Other situations: 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require medical or surgical treatment to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that 
do not result in hospitalization, or development of drug dependency or drug abuse. 
 
Events Meeting the AE/SAE Definition 
• Any abnormal laboratory test results (hematology or clinical chemistry) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and 
scientific judgment of the Investigator (i.e., not related to progression of underlying 
disease). 
• All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin ≥2 × ULN (>35% 
direct bilirubin) or ALT ≥3 × ULN and international normalized ratio (INR) >1.5, if 
INR measured, which may indicate severe liver injury (possible Hy’s Law), must be 
reported as an SAE. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication.  
• If on evaluation of diarrhea or other signs and symptom associate with CDI, no 
recurrence is deemed to have occurred, any symptoms (or preferably diagnosis) reported 
by the subject must be reported as AEs (up to Day 40) or as SAEs (anytime during the 
study if the event meets the definition of an SAE) 
• “Lack of efficacy" or "failure of expected pharmacological action" per se is not to be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfil the definition of an AE or SAE. 


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Events NOT Meeting the AE/SAE Definition 
Refer to Section 8.2.5 and Section 8.2.6  for events not meeting the AE/SAE definition. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• The Investigator will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the Investigator to send photocopies of the subject’s medical 
records to the SAE coordinator in lieu of completion of the AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested 
by the SAE coordinator or Medical Monitor. In this case, all subject identifiers, except 
for the subject number, will be redacted on the copies of the medical records before 
submission to the SAE coordinator. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
 
Assessment of Intensity 
The Investigator will assess intensity for each AE and SAE reported during the study and 
assign it to 1 of the following categories: 
• Mild: An event that is easily tolerated by the subject, causing minimal discomfort, and 
not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 Assessment of Causality 
• The Investigator is obligated to assess the relationship between study treatment 
(ridinilazole/vancomycin) and each occurrence of each AE/SAE as “related” or “not 
related” by answering the question: 


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o ‘‘Do you consider that there is a reasonable possibility that the adverse event 
has been caused by the study treatment?” 
• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
• The Investigator will consult both the Investigator’s Brochure (IB) for ridinilazole and 
the and/or Product Information for vancomycin, for marketed products, in his/her 
assessment. 
• There may be situations in which an SAE has occurred, and the Investigator has 
minimal information to include in the initial report to Pharmacovigilance (the SAE 
coordinator). However, it is very important that the Investigator always assess 
causality for every event before the initial transmission of the SAE data to the 
SAE coordinator. If there are limited or insufficient information about the event to 
make an informed judgment, and in the absence of any indication or evidence to 
establish a causal relationship, a causality assessment of “not related” is to be 
considered. In such instances, the Investigator is expected to obtain additional 
information regarding the event as soon as possible and to re-evaluate the causality 
upon receipt of additional information. 
• The causality assessment is important to be provided because it is one of the criteria 
used when determining regulatory/authority reporting requirements 
• The investigator is requested to provide an explanation for the causality assessment for 
each SAE and must document this in the medical notes, on the SAE form and in the 
eCRF. 
• Following a review of the relevant data, the causal relationship between the study 
treatment (vancomycin/ridinilazole) and each (S)AE will be assessed by answering 
‘yes’ or ‘no’ to the question: 
• “Do you consider that there is a reasonable possibility that the adverse event has been 
caused by the study treatment? “ 
• When making an assessment of causality, the following factors are to be considered 
when deciding if there is evidence and/or arguments to suggest there is a ‘reasonable 
possibility’ that an (S)AE may have been caused by the study treatment (rather than a 
relationship cannot be ruled out) or if there is evidence to reasonably deny a causal 
relationship: 
o Plausible temporal relationship between exposure to the study treatment and 
(S)AE onset and/or resolution. Has the subject actually received the study 
treatment? Did the (S)AE occur in a reasonable temporal relationship to the 
administration of the study treatment 


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o Plausibility; i.e., could the event have been caused by the study treatment? 
among others biologic and/or pharmacologic mechanism, half-life, and 
preclinical and clinical study data (information can be found in, the IB) or can 
the event be explained by the underlying disease(s) or concomitant drugs 
o De-challenge/Dose reduction/Re-challenge: 
o Did the (S)AE resolve or improve after stopping the dose of the study 
treatment. Also consider the impact of treatment for the event when evaluating 
a de-challenge experience. 
o Did the (S)AE re-occur when the suspected study treatment was reintroduced 
after having been stopped? 
o Laboratory or other test results; a specific laboratory investigation supports the 
assessment of the relationship between the (S)AE and the study treatment (e.g., 
based on values pre- during and post-treatment). 
o Available alternative explanations independent of study treatment exposure 
(such as other concomitant drugs, past medical history, concurrent or 
underlying disease, risk factors including medical and family history, season, 
location, etc.) and strength of the alternative explanation. 
• The Investigator may change his/her opinion of causality considering follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
 
Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the SAE 
coordinator to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• If a subject dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the SAE coordinator with a copy of any post-
mortem findings including histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 
• The Investigator will submit any updated SAE data to the SAE coordinator within 
24 hours of receipt of the information. 
 


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SAE Reporting to Pharmacovigilance via email 
• SAEs will be transmitted to IQVIA using the Serious Adverse Event Form, which must 
be completed and signed by a member of the study team and transmitted to IQVIA 
pharmacovigilance with 24 hours of awareness of the event. 
All initial and follow up SAE reports should be sent to IQVIA Drug safety Centre Email: 
QLS_SMT19969@iqvia.com 
• Country specific toll-free fax numbers for SAE reporting will also be provided in the 
investigator site file. 
• Initial notification by email does not replace the need for the Investigator to complete 
and sign the SAE eCRF pages within the designated reporting time frames. 
• Contacts for SAE reporting can be found in the Investigator Trial Site File. 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
If the subject has a uterus and ovaries and has experienced menarche and is not permanently 
sterile or postmenopausal (postmenopausal is defined as 12 consecutive months with no menses 
without an alternative medical cause) and is having vaginal sex with someone with a penis and 
testicles, pregnancy can be a risk. These subjects are of childbearing potential and are defined as 
women of childbearing potential (WOCBP). 
Highly Effective Contractive Methods 
A highly effective method of birth control is defined as one that results in a low failure rate 
(i.e., <1% per year) when used consistently and correctly. This includes implants, injectables, 
combined oral contraceptives, some intrauterine devices, sexual abstinence, or a vasectomized 
partner. A vasectomy or a condom used with a spermicide is a medically acceptable form of birth 
control for males 
Contraception Guidance  
Male Subjects 
Male subjects must use a barrier contraceptive method during sexual intercourse with a woman of 
childbearing age or abstain from sexual intercourse during the study if it is their preferred and 
usual lifestyle. 
Agree to use a male condom plus partner use of a contraceptive method with a failure rate of <1% 
per year as described in Table 4 when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant 
In addition, male subjects must refrain from donating sperm for 30 days after the last dose of study 
treatment. 
Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration for 
30 days after the last dose of study treatment. 
Female Subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in Table 4. 


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Table 4: 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationb 
• Oral 
• Intravaginal 
• Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• Oral 
• Injectable 
Highly Effective Methods That Are User Independenta 
Implantable progestogen only hormonal contraception associated with inhibition of 
ovulationb 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method if the partner is the sole 
male sexual partner of the WOCBP If not, an additional highly effective method of 
contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the treatment period and continuing for 30 days after the end 
of study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the subject. 
NOTES: 
a. Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for subjects 
participating in clinical studies. 
b. Hormonal contraception may be susceptible to interaction with the study treatment, which may 
reduce the efficacy of the contraceptive method. In this case, two highly effective methods of 
contraception should be utilized during the treatment period and for at least 30 days after the last 
dose of study treatment 
Pregnancy Testing 
• WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive urine or serum pregnancy test (a urine test will be provided by the 
Central Laboratory). 


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• Pregnancy testing will be performed at Day 1 and whenever a menstrual cycle is missed 
or when pregnancy is otherwise suspected up to 30 days after the last dose of study 
treatment. 
Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study up to 30 days 
following the last dose of study treatment. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the Sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
Female Subjects who become pregnant 
• The Investigator will collect pregnancy information on any female subject who becomes 
pregnant up to 30 days after the last dose of study treatment. Information will be recorded 
on the appropriate form and submitted to the Sponsor within 24 hours of learning of a 
subject's pregnancy. The subject will be followed to determine the outcome of the 
pregnancy. The Investigator will collect follow-up information on the subject and the 
neonate, and the information will be forwarded to the Sponsor. Generally, follow-up will 
not be required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or SAE. 
A spontaneous abortion is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to the Sponsor as described in Section 8.3. 
While the Investigator is not obligated to actively seek this information in former study 
subjects, he or she may learn of an SAE through spontaneous reporting. 
 


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10.5. 
Appendix 5: Bristol Stool Chart 
 


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10.6. 
Appendix 6 Abbreviations 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AOC 
Assessment of cure 
AST 
Aspartate Amino Transferase 
bid 
Bis in die (twice daily) 
BLQ 
Below the level of quantification 
BUN 
Blood Urea Nitrogen 
CCNA 
Cell Cytotoxicity Neutralization Assay 
CDAD 
Clostridioides difficile-associated diarrhea 
CDI 
Clostridioides difficile infection (formerly known as Clostridium difficile) 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum observed plasma concentration 
CMH 
Cochran Mantel Haenszel 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus Disease 2019 
eCRF 
Electronic Case report form 
CRO 
Contract Research Organization 
DRE 
Disease related event 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
EMA 
European Medicines Agency 
EOS 
End of study 
EOT 
End of treatment 
EU 
European Union 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FDA 
Food and Drug Administration 
FSH 
Follicle-Stimulating Hormone 
FTT 
Free toxin test 
GC-MS 
Gas Chromatography Mass Spectrometry 
GCP 
Good clinical practice 
GDPR 
General Data Protection Regulation 
GI 
Gastrointestinal 
hCG 
Human Chorionic gonadotropin 
HEOR 
Health Economic Outcomes Research 
HIPAA 
Health Insurance Portability and Accountability Act 
HHC 
Home Healthcare 
HRT IB 
Hormone replacement therapy Investigator’s Brochure 


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IBD 
Inflammatory bowel disease 
i.v. 
Intravenous 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IDSA 
Infectious Diseases Society of America 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ration (for blood clotting time) 
IMP 
Investigational Medicinal Product 
IRB 
Institutional review board 
IRT 
Interactive Response Technology 
ITT 
Intention-to-treat 
IUD 
Intrauterine contraceptive device 
IUS 
Intrauterine system 
IVIG 
Intravenous immunoglobulin 
LLOQ 
Lower limit of quantification 
MCH MCV 
Mean Corpuscular Haemoglobin Mean Corpuscular Volume 
MIC 
Minimum inhibitory concentration 
MITT 
Modified intention-to-treat 
NOAEL 
No observable adverse effect level 
PD 
Pharmacodynamics 
PHI 
Protected Health Information 
PK 
Pharmacokinetics 
PP 
Per protocol 
PRO 
Subject Reported Outcome 
qid 
Quarter in die (four times daily) 
QTc(F) 
QT interval corrected according to Fridericia’s formula 
RBC 
Red Blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SCR 
Sustained clinical response 
SD 
Standard deviation 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SOA 
Schedule of Activities 
SOP 
Standard operating procedure 
SPC 
Summary of Product Characteristics 
SUSAR 
Suspected unexpected serious adverse reactions 
TEAE 
Treatment Emergent Adverse Event 
TMF 
Trial master file 


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TOC 
Test of Cure 
UBM 
Unformed bowel movements 
ULN 
Upper limit of normal 
VAS 
Visual Analogue Scale 
VC 
Video Conference 
VRE 
vancomycin resistant Enterococci 
WBC 
White Blood Cell 
WOCBP 
Woman of childbearing potential 


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10.7. 
References 
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