MODIFY I: A Study of MK-3415, MK-6072, and MK-3415A in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-001)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01241552
• Collaborator: (none)
• Enrollment: 1,452
• Arms: 4
• Actual Duration (Months): 38

Study Details

Study Description

Brief Summary

This study will investigate whether: 1) treatment with MK-3415A in addition to standard of care (SOC) antibiotic therapy will decrease Clostridium difficile infection (CDI) recurrence as compared to treatment with MK-6072 or MK-3415, 2) treatment with MK-3415A, MK-6072, or MK-3415, in addition to SOC antibiotic therapy will decrease CDI recurrence as compared to placebo, and 3) MK-3415A, MK-6072, and MK-3415 will be generally well tolerated in participants receiving SOC therapy for CDI as compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile Infection	Biological: MK-3415; Biological: MK-6072; Biological: MK-3415A; Biological: Placebo; Drug: SOC	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1452 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium Difficile Toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and Toxin B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY I)
• Actual Study Start Date: Oct 10, 2011
• Actual Primary Completion Date: Dec 9, 2014
• Actual Study Completion Date: Dec 9, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MK-3415 + SOC Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Biological: MK-3415; A single IV infusion of MK-3415 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A); Drug: SOC; Standard of care (SOC) for CDI will be prescribed for 10 to 14 days and can begin on the day of study drug infusion; but the first dose must have been administered prior to or within a few hours following study drug infusion. SOC is defined as the receipt of oral metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Experimental: MK-6072 + SOC Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Biological: MK-6072; A single infusion of MK-6072 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin B); Drug: SOC; Standard of care (SOC) for CDI will be prescribed for 10 to 14 days and can begin on the day of study drug infusion; but the first dose must have been administered prior to or within a few hours following study drug infusion. SOC is defined as the receipt of oral metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Experimental: MK-3415A + SOC Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Biological: MK-3415A; A single IV infusion of MK-3415A (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A and 10mg/kg of monoclonal antibody to Clostridium difficile Toxin B); Drug: SOC; Standard of care (SOC) for CDI will be prescribed for 10 to 14 days and can begin on the day of study drug infusion; but the first dose must have been administered prior to or within a few hours following study drug infusion. SOC is defined as the receipt of oral metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.
Placebo Comparator: Placebo + SOC Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI	Biological: Placebo; A single IV infusion of normal saline (0.9% sodium chloride); Drug: SOC; Standard of care (SOC) for CDI will be prescribed for 10 to 14 days and can begin on the day of study drug infusion; but the first dose must have been administered prior to or within a few hours following study drug infusion. SOC is defined as the receipt of oral metranidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clostridium Difficile Infection (CDI) Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic Clostridium (C.) difficile following clinical cure of the initial CDI episode

2. Percentage of Participants With One or More Adverse Events (AEs) During 4 Weeks Following Infusion [Up to 28 days]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

3. Percentage of Participants With Any Drug-related AE During 4 Weeks Following Infusion [Up to 28 days]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was an AE determined by the investigator to be related to the drug.

4. Percentage of Participants With Any Serious Adverse Events (SAEs) During 4 Weeks Following Infusion [Up to 28 days]

   A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events.

5. Percentage of Participants With Any Serious Drug-related Adverse Events During 4 Weeks Following Infusion [Up to 28 days]

   A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events. A serious drug-related AE was a SAE determined by the investigator to be related to the drug.

6. Percentage of Participants Who Discontinued Study Medication Due to an AE During 4 Weeks Following Infusion [Up to 28 days]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

7. Percentage of Participants With Infusion-specific AEs [Up to 24 hours]

   Infusion-specific AEs included local infusion site AEs; and systemic AEs which include nausea, vomiting, chills, fatigue, feeling hot, infusion site conditions (bruising, coldness, erythema, extravasation, pain, phlebitis, pruritus), pyrexia, arthralgia, musculoskeletal pain, myalgia, dizziness, headache, dysphonia, nasal congestion, pruritus, rash, pruritic rash, urticaria, flushing, hot flush, hypertension, and hypotension.

Secondary Outcome Measures

1. Percentage of Participants With Global Cure [Up to 12 weeks]

   Global Cure is defined as the clinical cure of the initial CDI episode and no CDI recurrence through Week 12. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the initial CDI episode.

2. Percentage of Participants With CDI Recurrence in Those With Clinical Cure of the Initial CDI Episode [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the baseline CDI episode.

3. Percentage of Participants ≥ 65 Years of Age at Study Entry With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.

4. Percentage of Participants With a History of CDI in the 6 Months Prior to Enrollment With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.

5. Percentage of Participants With Clinically Severe CDI at Study Entry With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinically severe CDI is defined as a Zar Score ≥ 2 based on the presence of 1 or more of the following: 1) age >60 years old (1 point); 2)body temperature >38.3°C (>100°F) (1 point); 3) albumin level ˂2.5 mg/dL (1 point); 4) peripheral white blood cell count >15,000 cells/mm^3 within 48 hours (1 point); 5) endoscopic evidence of pseudomembranous colitis (2 points); and 6) treatment in Intensive Care Unit (2 points).

6. Percentage of Participants With the B1/NAP1/027 Strain of C. Difficile at Study Entry With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.

7. Percentage of Participants With an Epidemic Strain of C. Difficile (Ribotypes 027, 014, 002, 001, 106, and 020) at Study Entry With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.

8. Percentage of Participants With Compromised Immunity at Study Entry With CDI Recurrence [Up to 12 weeks]

   CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Compromised immunity is defined as follows: an active hematological malignancy (including leukemia, lymphoma, multiple myeloma), an active malignancy requiring recent cytotoxic chemotherapy, receipt of a prior hematopoietic stem cell transplant, receipt of a prior solid organ transplant, asplenia, or neutropenia/pancytopenia due to other conditions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• participant has a confirmed diagnosis of CDI as defined by: a. diarrhea, as defined by passage of 3 or more loose stools in 24 or fewer hours, AND b. A positive test for toxigenic C. difficile from a stool collected no more than 7 days before study infusion.

• participant must be receiving SOC therapy for CDI. SOC therapy is defined as the receipt of oral metronidazole, oral vancomycin, IV metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.

• participant is highly unlikely to become pregnant or to impregnate a partner since they meet at least one of the following criteria: a. A female participant who is not of reproductive potential is eligible without requiring the use of contraception. A female participant who is not of reproductive potential is defined as: one who has either (1) reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea); (2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy; or (3) bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g. anorexia nervosa). b. A participant who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control starting at enrollment and through the 12 Week study period. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy and any registered and marketed hormonal contraceptives that contain an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents)

• participant or legal representative must have voluntarily agreed to participate by providing written informed consent after the nature of the study has been fully explained.

Exclusion Criteria:

• participant with an uncontrolled chronic diarrheal illness such that their normal 24-hour bowel movement habit is 3 or more loose stools.

• participant with a planned surgery for CDI within 24 hours.

• participant has a positive pregnancy test in the 48 hours before the infusion or is unwilling to undergo pregnancy testing if a pre-menopausal female who is not sterilized and therefore has the potential to bear a child.

• participant is breast-feeding or plans to breast-feed prior to the completion of the 12-week study period.

• A female participant who plans to donate ova prior to the completion of the 12-week study period, or a male participant who is planning to impregnate or provide sperm donation prior to the completion of the 12-week study period.

• participant has previously participated in this study, has previously received MK-3415 or MK- 6072 (either alone or in combination), has received a C. difficile vaccine, or has received another experimental monoclonal antibody against C. difficile toxin A or

• participant plans to donate blood and/or blood products within 6 months following the infusion.

• participant has received immune globulin within 6 months prior to receipt of the infusion or is planning to receive immune globulin prior to the completion of the 12-week study period.

• treatment with SOC therapy is planned for longer than 14 days.

• participant has received more than a 24-hour regimen of cholestyramine, colestimide, rifaximin, or nitazoxanide within 14 days prior to receipt of the infusion or is planning to receive these medications prior to the completion of the 12-week study period.

• participant plans to take medications that are given to decrease gastrointestinal peristalsis, such as loperamide (Imodium™) or diphenoxylate hydrochloride/atropine sulfate (LOMOTIL™), at any time during the 14 days following infusion. Participants receiving opioid medications at the onset of diarrhea may be included if they are on a stable dose or if there is anticipation of a dose decrease or cessation of use.

• participant plans to take the probiotic Saccharomyces boulardii or receive fecal transplant therapy, or any other therapies that have been demonstrated to decrease CDI recurrences at any time following infusion (Day 1) and through the completion of the 12-week study period.

• participant has received another investigational study agent within the previous 30 days, or is currently participating in or scheduled to participate in any other clinical trial with an investigational agent during the 12-week study period.

• participant is not expected to survive for 72 hours.

• participant has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant participating in the study, would make it unlikely for the participant to complete the study, or would confound the results of the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01241552
• Other Study ID Numbers: 3415A-001
• First Posted: Nov 16, 2010
• Last Update Posted: Sep 5, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Merck Sharp & Dohme LLC: Clostridium difficile; recurrent Clostridium difficile; vancomycin; metronidazole; monoclonal antibody; Clostridium difficile infection (CDI)
• Additional relevant MeSH terms: Infections; Communicable Diseases; Clostridium Infections; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	Participants 18 years of age or older, with a diagnosis of Clostridium difficile Infection (CDI) were enrolled in this trial.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care (SOC) for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Period Title: Overall Study
STARTED	242	403	403	404
Treated	235	392	388	397
COMPLETED	201	340	343	340
NOT COMPLETED	41	63	60	64

Baseline Characteristics

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC	Total
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI	Total of all reporting groups
Overall Participants	242	403	403	404	1452
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.2 (16.8)	61.1 (18.5)	62.5 (17.8)	62.9 (18.3)	62.5 (18.0)
Sex: Female, Male (Count of Participants)
Female	137 56.6%	238 59.1%	224 55.6%	230 56.9%	829 57.1%
Male	105 43.4%	165 40.9%	179 44.4%	174 43.1%	623 42.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clostridium Difficile Infection (CDI) Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic Clostridium (C.) difficile following clinical cure of the initial CDI episode
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	232	386	383	395
Number [Percentage of participants]	25.9 10.7%	17.4 4.3%	15.9 3.9%	27.6 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3182
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -8.6 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-10.1
	Confidence Interval	(2-Sided) 95%; -15.9 to -4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-11.6
	Confidence Interval	(2-Sided) 95%; -17.4 to -5.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - Placebo + SOC

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-9.9
	Confidence Interval	(2-Sided) 95%; -16.9 to -3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2997
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -6.7 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC

2. Secondary Outcome

Title	Percentage of Participants With Global Cure
Description	Global Cure is defined as the clinical cure of the initial CDI episode and no CDI recurrence through Week 12. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the initial CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	232	386	383	395
Number [Percentage of participants]	47.0 19.4%	60.1 14.9%	58.7 14.6%	55.2 13.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9775
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-8.3
	Confidence Interval	(2-Sided) 95%; -16.3 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0861
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95%; -2.1 to 11.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1646
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -3.5 to 10.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - Placebo + SOC

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	11.7
	Confidence Interval	(2-Sided) 95%; 3.5 to 19.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6532
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -8.3 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC

3. Secondary Outcome

Title	Percentage of Participants With CDI Recurrence in Those With Clinical Cure of the Initial CDI Episode
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the baseline CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; complied with Good Clinical Practice; and achieved clinical cure of the initial CDI episode.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	169	299	286	327
Number [Percentage of participants]	35.5 14.7%	22.4 5.6%	21.3 5.3%	33.3 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6505
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -6.9 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-10.8
	Confidence Interval	(2-Sided) 95%; -17.7 to -3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-11.7
	Confidence Interval	(2-Sided) 95%; -18.6 to -4.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - Placebo + SOC

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-13.7
	Confidence Interval	(2-Sided) 95%; -22.5 to -5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, MK-3415A + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3906
	Comments	One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Adjusted Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -7.7 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC

4. Primary Outcome

Title	Percentage of Participants With One or More Adverse Events (AEs) During 4 Weeks Following Infusion
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	67.2 27.8%	65.4 16.2%	59.7 14.8%	62.0 15.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 12.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -3.3 to 10.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -9.1 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

5. Primary Outcome

Title	Percentage of Participants With Any Drug-related AE During 4 Weeks Following Infusion
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was an AE determined by the investigator to be related to the drug.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	7.2 3%	8.2 2%	6.2 1.5%	5.0 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.246
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -1.5 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -0.3 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -2.1 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

6. Primary Outcome

Title	Percentage of Participants With Any Serious Adverse Events (SAEs) During 4 Weeks Following Infusion
Description	A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	27.7 11.4%	21.5 5.3%	14.7 3.6%	20.0 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; 0.9 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.594
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -4.1 to 7.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -10.6 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

7. Primary Outcome

Title	Percentage of Participants With Any Serious Drug-related Adverse Events During 4 Weeks Following Infusion
Description	A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events. A serious drug-related AE was a SAE determined by the investigator to be related to the drug.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	1.3 0.5%	1.0 0.2%	0.5 0.1%	0.3 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.115
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.170
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.5 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.544
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placeb + SOC

8. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Medication Due to an AE During 4 Weeks Following Infusion
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	0.4 0.2%	0.3 0.1%	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.192
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.5 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.311
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> 0.999
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

9. Primary Outcome

Title	Percentage of Participants With Infusion-specific AEs
Description	Infusion-specific AEs included local infusion site AEs; and systemic AEs which include nausea, vomiting, chills, fatigue, feeling hot, infusion site conditions (bruising, coldness, erythema, extravasation, pain, phlebitis, pruritus), pyrexia, arthralgia, musculoskeletal pain, myalgia, dizziness, headache, dysphonia, nasal congestion, pruritus, rash, pruritic rash, urticaria, flushing, hot flush, hypertension, and hypotension.
Time Frame	Up to 24 hours

Outcome Measure Data

Analysis Population Description

All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	235	390	387	400
Number [Percentage of participants]	11.1 4.6%	11.8 2.9%	8.8 2.2%	7.5 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -1.0 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; 0.2 to 8.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -2.6 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

10. Secondary Outcome

Title	Percentage of Participants ≥ 65 Years of Age at Study Entry With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants ≥ 65 years of age at study entry who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	122	185	200	199
Number [Percentage of participants]	26.2 10.8%	15.1 3.7%	17.0 4.2%	33.2 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) 95%; -16.8 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-18.0
	Confidence Interval	(2-Sided) 95%; -26.3 to -9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-16.2
	Confidence Interval	(2-Sided) 95%; -24.5 to -7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

11. Secondary Outcome

Title	Percentage of Participants With a History of CDI in the 6 Months Prior to Enrollment With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with a history of CDI in the 6 months prior to enrollment who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	69	103	96	109
Number [Percentage of participants]	33.3 13.8%	26.2 6.5%	25.0 6.2%	39.4 9.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -20.1 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-13.2
	Confidence Interval	(2-Sided) 95%; -25.5 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-14.4
	Confidence Interval	(2-Sided) 95%; -26.8 to -1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

12. Secondary Outcome

Title	Percentage of Participants With Clinically Severe CDI at Study Entry With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinically severe CDI is defined as a Zar Score ≥ 2 based on the presence of 1 or more of the following: 1) age >60 years old (1 point); 2)body temperature >38.3°C (>100°F) (1 point); 3) albumin level ˂2.5 mg/dL (1 point); 4) peripheral white blood cell count >15,000 cells/mm^3 within 48 hours (1 point); 5) endoscopic evidence of pseudomembranous colitis (2 points); and 6) treatment in Intensive Care Unit (2 points).
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with clinically severe CDI at study entry who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	31	67	62	60
Number [Percentage of participants]	25.8 10.7%	10.4 2.6%	12.9 3.2%	25.0 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -16.9 to 21.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-14.6
	Confidence Interval	(2-Sided) 95%; -28.3 to -1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-12.1
	Confidence Interval	(2-Sided) 95%; -26.2 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

13. Secondary Outcome

Title	Percentage of Participants With the B1/NAP1/027 Strain of C. Difficile at Study Entry With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with the B1/NAP1/027 strain of C. difficile at study entry who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	24	46	37	36
Number [Percentage of participants]	33.3 13.8%	26.1 6.5%	10.8 2.7%	36.1 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-10.0
	Confidence Interval	(2-Sided) 95%; -30.1 to 10.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-25.3
	Confidence Interval	(2-Sided) 95%; -43.7 to -6.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

14. Secondary Outcome

Title	Percentage of Participants With an Epidemic Strain of C. Difficile (Ribotypes 027, 014, 002, 001, 106, and 020) at Study Entry With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with an epidemic strain of C. difficile at study entry who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	57	108	106	106
Number [Percentage of participants]	24.6 10.2%	23.1 5.7%	19.8 4.9%	35.8 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-11.3
	Confidence Interval	(2-Sided) 95%; -24.9 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-12.7
	Confidence Interval	(2-Sided) 95%; -24.7 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-16.0
	Confidence Interval	(2-Sided) 95%; -27.8 to -4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

15. Secondary Outcome

Title	Percentage of Participants With Compromised Immunity at Study Entry With CDI Recurrence
Description	CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Compromised immunity is defined as follows: an active hematological malignancy (including leukemia, lymphoma, multiple myeloma), an active malignancy requiring recent cytotoxic chemotherapy, receipt of a prior hematopoietic stem cell transplant, receipt of a prior solid organ transplant, asplenia, or neutropenia/pancytopenia due to other conditions.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with compromised immunity at study entry who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.

Arm/Group Title	MK-3415 + SOC	MK-6072 + SOC	MK-3415A + SOC	Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI	Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI	Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
Measure Participants	55	87	78	92
Number [Percentage of participants]	18.2 7.5%	17.2 4.3%	11.5 2.9%	28.3 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-3415 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-10.1
	Confidence Interval	(2-Sided) 95%; -23.2 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415 + SOC - Placebo + SOC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MK-6072 + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-11.0
	Confidence Interval	(2-Sided) 95%; -23.2 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-6072 + SOC - Placebo + SOC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MK-3415A + SOC, Placebo + SOC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-16.7
	Confidence Interval	(2-Sided) 95%; -28.4 to -4.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference: MK-3415A + SOC - Placebo + SOC

Adverse Events

Time Frame	Up to 90 days
Adverse Event Reporting Description	All randomized participants who received infusion of study medication, based on the treatment actually received. One participant randomized to receive MK-3415A, and two participants randomized to receive MK-6072 actually received placebo instead.
Arm/Group Title	MK-3415 + SOC		MK-6072 + SOC		MK-3415A + SOC		Placebo + SOC
Arm/Group Description	Single intravenous (IV) infusion of 10 mg/kg MK-3415 + SOC for CDI		Single IV infusion of 10 mg/kg MK-6072 + SOC for CDI		Single IV infusion of 10 mg/kg MK 3415A + SOC for CDI		Normal saline infusion (0.9% sodium chloride) + SOC for CDI
All Cause Mortality
	MK-3415 + SOC		MK-6072 + SOC		MK-3415A + SOC		Placebo + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MK-3415 + SOC		MK-6072 + SOC		MK-3415A + SOC		Placebo + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/235 (44.3%)		120/390 (30.8%)		94/387 (24.3%)		126/400 (31.5%)
Blood and lymphatic system disorders
Anaemia	2/235 (0.9%)	2	2/390 (0.5%)	2	1/387 (0.3%)	2	1/400 (0.3%)	1
Disseminated intravascular coagulation	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Febrile neutropenia	1/235 (0.4%)	1	2/390 (0.5%)	2	2/387 (0.5%)	2	1/400 (0.3%)	1
Iron deficiency anaemia	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Leukocytosis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Neutropenia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Pancytopenia	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Thrombocytopenia	1/235 (0.4%)	2	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	2/400 (0.5%)	2
Angina pectoris	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Angina unstable	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Atrial fibrillation	2/235 (0.9%)	2	2/390 (0.5%)	2	1/387 (0.3%)	1	0/400 (0%)	0
Atrial flutter	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Atrial tachycardia	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Bradycardia	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Bundle branch block left	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Cardiac arrest	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Cardiac disorder	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cardiac failure	3/235 (1.3%)	4	4/390 (1%)	4	1/387 (0.3%)	1	4/400 (1%)	4
Cardiac failure acute	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Cardiac failure chronic	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cardiac failure congestive	2/235 (0.9%)	3	1/390 (0.3%)	1	3/387 (0.8%)	3	2/400 (0.5%)	2
Cardio-respiratory arrest	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cardiopulmonary failure	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	2/400 (0.5%)	2
Hypertensive heart disease	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Intrapericardial thrombosis	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Myocardial infarction	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	1/400 (0.3%)	1
Palpitations	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Sinus arrhythmia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Tachycardia	2/235 (0.9%)	2	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Ventricular tachyarrhythmia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Ventricular tachycardia	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Ear and labyrinth disorders
Hearing impaired	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Eye disorders
Diplopia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	1/400 (0.3%)	1
Abdominal distension	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Abdominal hernia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Abdominal pain	4/235 (1.7%)	4	3/390 (0.8%)	3	4/387 (1%)	4	2/400 (0.5%)	2
Abdominal pain lower	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Abdominal pain upper	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Acute abdomen	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Ascites	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	1/400 (0.3%)	1
Colitis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Colitis ulcerative	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Constipation	3/235 (1.3%)	3	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Crohn's disease	1/235 (0.4%)	1	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Diarrhoea	6/235 (2.6%)	6	9/390 (2.3%)	10	6/387 (1.6%)	8	6/400 (1.5%)	7
Diarrhoea haemorrhagic	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Diverticular perforation	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Diverticulum	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Epiploic appendagitis	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Faecal incontinence	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Gastritis alcoholic	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Gastrointestinal haemorrhage	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	2/400 (0.5%)	2
Gastrointestinal inflammation	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Haematochezia	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Hernial eventration	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Ileus	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Incarcerated umbilical hernia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Inflammatory bowel disease	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Intestinal dilatation	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Intestinal obstruction	1/235 (0.4%)	1	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Large intestine perforation	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Melaena	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Nausea	3/235 (1.3%)	3	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Oesophageal stenosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Pancreatitis	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Pancreatitis acute	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	2/400 (0.5%)	3
Pancreatitis necrotising	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Proctalgia	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Rectal haemorrhage	2/235 (0.9%)	2	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Small intestinal obstruction	0/235 (0%)	0	0/390 (0%)	0	2/387 (0.5%)	2	1/400 (0.3%)	1
Umbilical hernia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Upper gastrointestinal haemorrhage	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	1/400 (0.3%)	1
Vomiting	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	1/400 (0.3%)	1
General disorders
Adverse drug reaction	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Asthenia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Chest pain	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	2/400 (0.5%)	2
Death	1/235 (0.4%)	1	1/390 (0.3%)	1	1/387 (0.3%)	1	1/400 (0.3%)	1
General physical health deterioration	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Hernia obstructive	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Malaise	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Multi-organ failure	1/235 (0.4%)	1	1/390 (0.3%)	1	1/387 (0.3%)	1	2/400 (0.5%)	2
Non-cardiac chest pain	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Peripheral swelling	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Pyrexia	2/235 (0.9%)	2	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Sudden cardiac death	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Sudden death	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	2/400 (0.5%)	2
Systemic inflammatory response syndrome	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hepatobiliary disorders
Cholangitis	0/235 (0%)	0	1/390 (0.3%)	1	3/387 (0.8%)	3	0/400 (0%)	0
Cholecystitis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cholecystitis acute	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Cholelithiasis	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Cirrhosis alcoholic	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hepatic cirrhosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hepatorenal syndrome	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Portal vein thrombosis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Immune system disorders
Acute graft versus host disease	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Acute graft versus host disease in intestine	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Graft versus host disease	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Graft versus host disease in gastrointestinal tract	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Heart transplant rejection	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Infections and infestations
Abdominal abscess	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	2/400 (0.5%)	2
Abdominal infection	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Abscess limb	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Arthritis bacterial	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Bacteraemia	1/235 (0.4%)	1	3/390 (0.8%)	3	3/387 (0.8%)	3	3/400 (0.8%)	3
Biliary tract infection	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Bronchitis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Bronchitis viral	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Bronchopneumonia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Bursitis infective	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Campylobacter gastroenteritis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Candida infection	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Cellulitis	1/235 (0.4%)	1	3/390 (0.8%)	4	0/387 (0%)	0	3/400 (0.8%)	4
Clostridium difficile infection	26/235 (11.1%)	28	10/390 (2.6%)	13	18/387 (4.7%)	21	26/400 (6.5%)	32
Clostridium difficile sepsis	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cystitis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Device related infection	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Device related sepsis	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Diverticulitis	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	2/400 (0.5%)	2
Empyema	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Encephalitis viral	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Erysipelas	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Gangrene	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Gas gangrene	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Gastroenteritis	0/235 (0%)	0	0/390 (0%)	0	3/387 (0.8%)	3	1/400 (0.3%)	1
Gastroenteritis viral	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Graft infection	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Histoplasmosis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Hypopyon	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Infected lymphocele	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Kidney infection	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Lobar pneumonia	1/235 (0.4%)	1	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Localised infection	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Lower respiratory tract infection	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Mediastinitis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Osteomyelitis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Peritonitis	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Pneumonia	7/235 (3%)	7	7/390 (1.8%)	7	5/387 (1.3%)	5	11/400 (2.8%)	11
Pneumonia bacterial	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Pneumonia haemophilus	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Post procedural infection	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Postoperative wound infection	0/235 (0%)	0	1/390 (0.3%)	1	2/387 (0.5%)	2	0/400 (0%)	0
Pseudomembranous colitis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Psoas abscess	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Pyelonephritis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	4
Respiratory tract infection	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Rhinovirus infection	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Salmonellosis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Sepsis	9/235 (3.8%)	9	7/390 (1.8%)	7	3/387 (0.8%)	3	11/400 (2.8%)	11
Septic shock	3/235 (1.3%)	3	3/390 (0.8%)	3	4/387 (1%)	4	4/400 (1%)	4
Soft tissue infection	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Systemic candida	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Systemic mycosis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Tracheitis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Tracheobronchitis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	2/400 (0.5%)	2
Upper respiratory tract infection	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Urinary tract infection	6/235 (2.6%)	7	6/390 (1.5%)	7	4/387 (1%)	4	5/400 (1.3%)	5
Urosepsis	1/235 (0.4%)	1	1/390 (0.3%)	1	1/387 (0.3%)	1	2/400 (0.5%)	2
Wound infection	0/235 (0%)	0	2/390 (0.5%)	2	1/387 (0.3%)	1	1/400 (0.3%)	1
Zygomycosis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Cervical vertebral fracture	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Contusion	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Fall	1/235 (0.4%)	1	1/390 (0.3%)	1	3/387 (0.8%)	3	0/400 (0%)	0
Gun shot wound	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Hip fracture	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Intestinal anastomosis complication	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Perinephric collection	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Post-traumatic pain	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Procedural vomiting	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Radiation oesophagitis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Rib fracture	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Investigations
Alanine aminotransferase increased	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Blood alkaline phosphatase increased	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Blood bilirubin increased	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Haemoglobin decreased	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Heart rate increased	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Platelet count decreased	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Metabolism and nutrition disorders
Dehydration	1/235 (0.4%)	1	2/390 (0.5%)	2	3/387 (0.8%)	3	5/400 (1.3%)	5
Electrolyte imbalance	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Failure to thrive	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	1/400 (0.3%)	1
Fluid overload	2/235 (0.9%)	2	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Gout	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hyperammonaemia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Hyperglycaemia	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Hyperglycaemic hyperosmolar nonketotic syndrome	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Hyperkalaemia	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	3/400 (0.8%)	4
Hypoglycaemia	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hypokalaemia	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Musculoskeletal and connective tissue disorders
Compartment syndrome	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Connective tissue disorder	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Flank pain	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Haemarthrosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Rhabdomyolysis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Spinal disorder	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Acute myeloid leukaemia recurrent	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Adenocarcinoma of colon	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Bladder transitional cell carcinoma	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Breast cancer	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Breast cancer metastatic	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Burkitt's lymphoma	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Colon cancer metastatic	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Gastric cancer	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Hypergammaglobulinaemia benign monoclonal	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Lung neoplasm malignant	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Malignant melanoma	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Malignant melanoma in situ	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Malignant neoplasm progression	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Metastases to spine	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Myelodysplastic syndrome	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Ovarian cancer metastatic	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Pancreatic carcinoma	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Squamous cell carcinoma	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Nervous system disorders
Aphasia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Cerebral haemorrhage	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Cerebral infarction	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Cerebrovascular accident	3/235 (1.3%)	3	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Convulsion	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	1/400 (0.3%)	1
Depressed level of consciousness	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Disturbance in attention	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Encephalopathy	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Epilepsy	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Headache	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Hepatic encephalopathy	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	1/400 (0.3%)	1
Metabolic encephalopathy	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Partial seizures	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Presyncope	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Subarachnoid haemorrhage	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Syncope	2/235 (0.9%)	3	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Transient ischaemic attack	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Psychiatric disorders
Affective disorder	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Aggression	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Alcoholism	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Confusional state	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Depression	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Drug dependence	0/235 (0%)	0	1/390 (0.3%)	2	0/387 (0%)	0	0/400 (0%)	0
Mental status changes	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	2/400 (0.5%)	2
Psychogenic seizure	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Suicide attempt	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Renal and urinary disorders
Bladder dilatation	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Haematuria	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Nephritis autoimmune	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Renal failure acute	3/235 (1.3%)	3	5/390 (1.3%)	5	3/387 (0.8%)	3	6/400 (1.5%)	6
Renal failure chronic	0/235 (0%)	0	3/390 (0.8%)	3	0/387 (0%)	0	1/400 (0.3%)	1
Renal impairment	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Urinary retention	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Aspiration	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Asthma	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Atelectasis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Chronic obstructive pulmonary disease	2/235 (0.9%)	2	2/390 (0.5%)	2	2/387 (0.5%)	2	1/400 (0.3%)	1
Chronic respiratory failure	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Cough	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Hypoxia	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Pharyngeal stenosis	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Pleural effusion	0/235 (0%)	0	1/390 (0.3%)	2	0/387 (0%)	0	3/400 (0.8%)	3
Pneumonia aspiration	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	2/400 (0.5%)	2
Pneumothorax	0/235 (0%)	0	2/390 (0.5%)	2	0/387 (0%)	0	0/400 (0%)	0
Pulmonary cavitation	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Pulmonary embolism	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Pulmonary oedema	0/235 (0%)	0	1/390 (0.3%)	1	1/387 (0.3%)	1	0/400 (0%)	0
Respiratory arrest	0/235 (0%)	0	0/390 (0%)	0	2/387 (0.5%)	2	0/400 (0%)	0
Respiratory disorder	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Respiratory failure	2/235 (0.9%)	2	2/390 (0.5%)	2	1/387 (0.3%)	1	4/400 (1%)	4
Sputum increased	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Skin and subcutaneous tissue disorders
Ecchymosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Eczema	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Rash	2/235 (0.9%)	2	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Skin ulcer	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Vascular disorders
Deep vein thrombosis	2/235 (0.9%)	2	1/390 (0.3%)	1	0/387 (0%)	0	1/400 (0.3%)	1
Haematoma	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Hypertension	1/235 (0.4%)	1	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Hypertensive crisis	0/235 (0%)	0	1/390 (0.3%)	1	0/387 (0%)	0	2/400 (0.5%)	2
Hypotension	2/235 (0.9%)	2	0/390 (0%)	0	1/387 (0.3%)	1	1/400 (0.3%)	1
Hypovolaemic shock	1/235 (0.4%)	1	1/390 (0.3%)	1	0/387 (0%)	0	0/400 (0%)	0
Peripheral arterial occlusive disease	1/235 (0.4%)	1	0/390 (0%)	0	0/387 (0%)	0	0/400 (0%)	0
Peripheral artery stenosis	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Peripheral artery thrombosis	0/235 (0%)	0	0/390 (0%)	0	1/387 (0.3%)	1	0/400 (0%)	0
Peripheral ischaemia	0/235 (0%)	0	0/390 (0%)	0	0/387 (0%)	0	1/400 (0.3%)	1
Other (Not Including Serious) Adverse Events
	MK-3415 + SOC		MK-6072 + SOC		MK-3415A + SOC		Placebo + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/235 (35.7%)		116/390 (29.7%)		110/387 (28.4%)		103/400 (25.8%)
Gastrointestinal disorders
Abdominal pain	14/235 (6%)	15	25/390 (6.4%)	32	20/387 (5.2%)	21	24/400 (6%)	28
Diarrhoea	18/235 (7.7%)	23	25/390 (6.4%)	33	33/387 (8.5%)	38	27/400 (6.8%)	42
Nausea	30/235 (12.8%)	33	32/390 (8.2%)	38	33/387 (8.5%)	40	30/400 (7.5%)	35
Vomiting	11/235 (4.7%)	13	23/390 (5.9%)	29	15/387 (3.9%)	18	16/400 (4%)	16
General disorders
Fatigue	12/235 (5.1%)	13	7/390 (1.8%)	7	14/387 (3.6%)	15	5/400 (1.3%)	5
Pyrexia	14/235 (6%)	18	23/390 (5.9%)	26	13/387 (3.4%)	16	15/400 (3.8%)	16
Infections and infestations
Urinary tract infection	15/235 (6.4%)	15	18/390 (4.6%)	18	15/387 (3.9%)	15	20/400 (5%)	21
Nervous system disorders
Headache	15/235 (6.4%)	19	20/390 (5.1%)	23	22/387 (5.7%)	23	14/400 (3.5%)	18

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.