Trial Outcomes & Findings for Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001) (NCT NCT01691248)

Last Updated: 2018-09-18

Results Overview

CDAD is defined as follows: Diarrhea: (change in bowel habits with \>3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

611 participants

Primary outcome timeframe

Up to 30 days post-treatment

Results posted on

2018-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Fidaxomicin 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo Placebo tablet once daily for no longer than 40 days
Overall Study STARTED	305	306
Overall Study Treated	301	299
Overall Study Safety Analysis Set	300	300
Overall Study COMPLETED	194	192
Overall Study NOT COMPLETED	111	114

Reasons for withdrawal

Reasons for withdrawal
Measure	Fidaxomicin 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo Placebo tablet once daily for no longer than 40 days
Overall Study Protocol Violation	43	27
Overall Study Adverse Event	24	22
Overall Study Withdrawal by Subject	20	18
Overall Study Confirmed CDAD	14	31
Overall Study Lost to Follow-up	2	5
Overall Study Reason not provided	4	4
Overall Study Not Treated	4	7

Baseline Characteristics

Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fidaxomicin n=301 Participants 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=299 Participants Placebo tablet once daily for no longer than 40 days	Total n=600 Participants Total of all reporting groups
Age, Continuous	55.1 Years STANDARD_DEVIATION 12.00 • n=5 Participants	55.1 Years STANDARD_DEVIATION 13.23 • n=7 Participants	55.1 Years STANDARD_DEVIATION 12.62 • n=5 Participants
Sex: Female, Male Female	125 Participants n=5 Participants	103 Participants n=7 Participants	228 Participants n=5 Participants
Sex: Female, Male Male	176 Participants n=5 Participants	196 Participants n=7 Participants	372 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days post-treatment

Population: mITT consisting of all randomized participants undergoing HSCT who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=301 Participants 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=299 Participants Placebo tablet once daily for no longer than 40 days
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.	28.6 Percentage of participants Interval 23.5 to 33.7	30.8 Percentage of participants Interval 25.5 to 36.0

SECONDARY outcome

Timeframe: Up to 60 days post-treatment

Population: mITT consisting of all randomized participants undergoing HSCT who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=301 Participants 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=299 Participants Placebo tablet once daily for no longer than 40 days
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.	35.2 Percentage of participants Interval 29.8 to 40.6	35.8 Percentage of participants Interval 30.4 to 41.2

SECONDARY outcome

Timeframe: Up to Day 70 of study

Population: mITT consisting of all randomized participants undergoing HSCT who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=301 Participants 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=299 Participants Placebo tablet once daily for no longer than 40 days
Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.	29.2 Percentage of participants Interval 24.1 to 34.4	31.1 Percentage of participants Interval 25.9 to 36.4

Adverse Events

Fidaxomicin

Serious events: 98 serious events

Other events: 297 other events

Deaths: 0 deaths

Placebo

Serious events: 92 serious events

Other events: 298 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication or other public presentation of results from this study requires prior review and written approval of the Sponsor. Draft abstracts, manuscripts, and materials for presentation at scientific meetings should be provided to the Sponsor at least 90 working days prior to abstract or other relevant submission deadlines.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Fidaxomicin n=300 participants at risk 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=300 participants at risk Placebo tablet once daily for no longer than 40 days
General disorders Oedema peripheral	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Pyrexia	1.7% 5/300 • Number of events 5 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	3.3% 10/300 • Number of events 10 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Systemic inflammatory response syndrome	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Hepatobiliary disorders Cholecystitis acute	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Hepatobiliary disorders Hepatic failure	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Hepatobiliary disorders Hepatic function abnormal	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Hepatobiliary disorders Portal hypertension	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Hepatobiliary disorders Venoocclusive liver disease	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Multi-organ failure	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Mucosal inflammation	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	1.0% 3/300 • Number of events 3 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Anaemia	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Febrile neutropenia	5.7% 17/300 • Number of events 18 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	4.7% 14/300 • Number of events 14 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Pancytopenia	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Splenic haemorrhage	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Atrial fibrillation	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Cardiac arrest	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Cardiac failure acute	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Cardiac failure congestive	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 3 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Pericarditis	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Sinus tachycardia	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Eye disorders Blindness	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Abdominal distension	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Abdominal pain	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.67% 2/300 • Number of events 3 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Ascites	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Diarrhoea	1.7% 5/300 • Number of events 5 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Enterocolitis	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Haematochezia	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Nausea	1.7% 5/300 • Number of events 5 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Neutropenic colitis	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Oesophagitis	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Stomatitis	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Vomiting	2.3% 7/300 • Number of events 7 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Adverse drug reaction	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Asthenia	0.67% 2/300 • Number of events 2 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Chest pain	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Chills	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Inflammation	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.00% 0/300 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Immune system disorders Acute graft versus host disease	1.0% 3/300 • Number of events 3 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	0.33% 1/300 • Number of events 1 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.

Other adverse events
Measure	Fidaxomicin n=300 participants at risk 200 mg Fidaxomicin tablet once daily for no longer than 40 days	Placebo n=300 participants at risk Placebo tablet once daily for no longer than 40 days
Metabolism and nutrition disorders Hypophosphataemia	12.3% 37/300 • Number of events 39 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	9.0% 27/300 • Number of events 28 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 13/300 • Number of events 21 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	8.3% 25/300 • Number of events 29 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Musculoskeletal and connective tissue disorders Back pain	11.0% 33/300 • Number of events 37 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	13.3% 40/300 • Number of events 46 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.3% 10/300 • Number of events 10 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.3% 16/300 • Number of events 20 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Musculoskeletal and connective tissue disorders Pain in extremity	9.3% 28/300 • Number of events 34 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	9.7% 29/300 • Number of events 31 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Anaemia	13.3% 40/300 • Number of events 63 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	12.0% 36/300 • Number of events 52 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Febrile neutropenia	42.7% 128/300 • Number of events 131 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	32.7% 98/300 • Number of events 107 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Neutropenia	10.3% 31/300 • Number of events 63 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	13.3% 40/300 • Number of events 65 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Blood and lymphatic system disorders Thrombocytopenia	18.0% 54/300 • Number of events 77 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	15.3% 46/300 • Number of events 77 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Sinus tachycardia	4.3% 13/300 • Number of events 14 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.3% 16/300 • Number of events 16 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Cardiac disorders Tachycardia	10.0% 30/300 • Number of events 39 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	14.3% 43/300 • Number of events 59 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Abdominal distension	5.3% 16/300 • Number of events 17 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	4.0% 12/300 • Number of events 14 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Abdominal pain	20.7% 62/300 • Number of events 71 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	21.0% 63/300 • Number of events 83 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Abdominal pain upper	6.7% 20/300 • Number of events 20 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.3% 16/300 • Number of events 24 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Constipation	18.3% 55/300 • Number of events 59 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	29.3% 88/300 • Number of events 107 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Diarrhoea	70.3% 211/300 • Number of events 286 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	73.3% 220/300 • Number of events 340 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Dry mouth	7.3% 22/300 • Number of events 24 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	10.7% 32/300 • Number of events 34 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Dyspepsia	14.7% 44/300 • Number of events 47 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	11.0% 33/300 • Number of events 35 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 15/300 • Number of events 15 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	6.0% 18/300 • Number of events 19 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Haemorrhoids	6.0% 18/300 • Number of events 18 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	8.7% 26/300 • Number of events 27 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Nausea	61.3% 184/300 • Number of events 252 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	67.0% 201/300 • Number of events 284 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Oesophagitis	9.7% 29/300 • Number of events 29 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	8.0% 24/300 • Number of events 25 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Stomatitis	22.7% 68/300 • Number of events 89 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	25.0% 75/300 • Number of events 103 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Gastrointestinal disorders Vomiting	39.7% 119/300 • Number of events 174 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	41.0% 123/300 • Number of events 172 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Asthenia	7.3% 22/300 • Number of events 31 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	12.7% 38/300 • Number of events 47 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Chills	9.3% 28/300 • Number of events 33 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	10.3% 31/300 • Number of events 39 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Fatigue	39.0% 117/300 • Number of events 138 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	39.3% 118/300 • Number of events 149 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Mucosal inflammation	35.7% 107/300 • Number of events 128 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	35.3% 106/300 • Number of events 134 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Oedema peripheral	26.0% 78/300 • Number of events 99 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	21.0% 63/300 • Number of events 74 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
General disorders Pyrexia	23.0% 69/300 • Number of events 83 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	30.3% 91/300 • Number of events 103 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Infections and infestations Oral candidiasis	5.7% 17/300 • Number of events 17 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.0% 15/300 • Number of events 15 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Investigations Aspartate aminotransferase increased	4.0% 12/300 • Number of events 15 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.7% 17/300 • Number of events 24 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Investigations Blood creatinine increased	4.3% 13/300 • Number of events 16 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	7.0% 21/300 • Number of events 23 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Investigations Haemoglobin decreased	2.3% 7/300 • Number of events 11 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	5.3% 16/300 • Number of events 33 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Investigations Platelet count decreased	5.7% 17/300 • Number of events 26 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	7.0% 21/300 • Number of events 31 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Metabolism and nutrition disorders Decreased appetite	32.3% 97/300 • Number of events 117 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	35.3% 106/300 • Number of events 127 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Metabolism and nutrition disorders Fluid overload	10.0% 30/300 • Number of events 30 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	9.7% 29/300 • Number of events 31 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Metabolism and nutrition disorders Hyperglycaemia	4.3% 13/300 • Number of events 17 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	7.0% 21/300 • Number of events 27 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Metabolism and nutrition disorders Hypocalcaemia	7.0% 21/300 • Number of events 25 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	4.3% 13/300 • Number of events 18 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.
Metabolism and nutrition disorders Hypokalaemia	15.0% 45/300 • Number of events 53 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.	14.7% 44/300 • Number of events 52 • Non-serious adverse events (AEs) up to 32 days post treatment. Serious AEs (SAEs) up to 62 days post treatment. Participants who received at least one dose of study drug. One participant randomized to Fidaxomicin, received placebo instead.