A Clinical Trial to Assess Three Different Doses of OPS-2071 in Patients With Bacterial Enteritis

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02473393
• Collaborator: (none)
• Enrollment: 43
• Locations: 3
• Arms: 4
• Actual Duration (Months): 18.8
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

To assess safety, efficacy and pharmacokinetics of multiple dosesin patients with Bacterial Enteritis caused by Clostridium difficile infection(CDI) or Enteric infection.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Enteritis	Drug: OPS-2071 tablet	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Aug 20, 2015
• Actual Primary Completion Date: Mar 14, 2017
• Actual Study Completion Date: Mar 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPS-2071 50mg/day OPS-2071 50 mg/day：25 mg tablet administered orally twice daily	Drug: OPS-2071 tablet
Experimental: OPS-2071 100 mg/day OPS-2071 100 mg/day：50 mg tablet administered orally twice daily	Drug: OPS-2071 tablet
Experimental: OPS-2071 200 mg/day OPS-2071 200 mg/day：100 mg tablet administered orally twice daily	Drug: OPS-2071 tablet
Experimental: OPS-2071 400 mg/day OPS-2071 400 mg/day：100 mg two tablets administered orally twice daily	Drug: OPS-2071 tablet

Outcome Measures

Primary Outcome Measures

1. Bacterial Elimination Rate (BER) in the CDI and EI Groups [CDI group: screening, Day 4 and Day 11 (end of treatment), EI group: screening, Day 4 and Day 8 (end of treatment)]

   Judged according to the assessment criteria for the bacterial strain isolated as the causative pathogen based on the data from the microbiological examination. Analysis was performed by disease group and by dose, and by minimum inhibitory concentration (MIC) values of OPS-2071 for each of the causative strains (Enterotoxigenic E. coli, Enteroaggregative E. coli, Campylobacter sp., C. jejuni, S. aureus, K. oxytoca, and C. perfringens for the EI group). Data were shown as all strains total. Concerning microbiological outcome by causative strain, bacteria elimination rate (BER) and its 95% confidence interval (CI) were calculated. The BER was the proportion of causative strains assessed as either "Excellent" or "Good" except for those assessed as "unknown/indeterminate".

2. Maximum Plasma Concentration (Cmax) of OPS-2071 on Day 4 [Inpatient: 1h, 2h, and 4h after morning administration]

   We measured OPS-2071 concentration in plasma and evaluated Cmax of OPS-2071 in plasma.

3. Time to Maximum Plasma Concentration (Tmax) of OPS-2071 on Day 4 [1h, 2h, and 4h after morning administration]

   We measured OPS-2071 concentration in plasma and evaluated tmax of OPS-2071 in plasma.

Secondary Outcome Measures

1. The Recurrence Rate of CDI After Multiple Doses of OPS-2071 (for CDI Group Only) [Day 38]

   CDI recurrence rate at follow-up (Day 38) or withdrawal was calculated. CDI recurrence rate was the proportion of the subjects judged as "recurrent" against evaluable subjects, except for those with missing data.

2. The Time to Resolution of Diarrhea After Multiple Doses of OPS-2071 [CDI group: Day 4, Day 11 (end of treatment) and Day 38, EI group: Day 4 and Day 8 (end of treatment)]

   The time from the start of dosing until the first formed stool (except in cases where liquid or unformed stools recurred) was evaluated as time to resolution of diarrhea. If formed stool has not been observed, then the subject will be handled as missing data.

3. Stool Frequency Per Day After Multiple Doses of OPS-2071 [CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)]

   Under each disease group, the improvement of clinical symptoms (stool frequency/day) were assessed.

4. Number of Subjects With Formed Stool, Liquid or Unformed Stool, and Bloody Stool After Multiple Doses of OPS-2071 [CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)]

   Under each disease group, the improvement of clinical symptoms ((i.e. formed stool, liquid or unformed stool [3 and more times], and presence of bloody stool) were assessed.

5. Number of Subjects With Abdominal Pain, Nausea, and Vomiting After Multiple Doses of OPS-2071 [CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)]

   Under each disease group, he improvement of clinical symptoms (i.e. presence of abdominal pain, nausea, and vomiting) were assessed.

6. Clinical Response Rate (CRR) in the CDI and EI Groups [CDI group: Day 4 and Day 11 (end of treatment), EI group: Day 4 and Day 8 (end of treatment)]

   The CRR and 95% CI at each evaluation time point were calculated. The CRR was calculated as the proportion of the subjects judged as "clinical cure" or "clinical improvement" against evaluable subjects, except for those with missing data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient provides written, informed consent before the clinical trial is initiated

• The patient has distinctive symptoms and findings of bacterial enteritis

• The patient has bacterial enteritis with one or more of the following causative pathogens either proven or presumed: C. difficile, Salmonella, Campylobacter, pathogenic E. coli, and other bacteria estimated to cause bacterial enteritis

• The patient and his/her partner are willing to take contraceptive measures from initiation of investigational medicinal products (IMPs) to 4 weeks after administration of IMPs

Exclusion Criteria:

• The patient has severe or progressive underlying disease or complication, making it difficult to ensure safety in the study or proper efficacy assessment

• The patient has a current diagnosis or history of convulsive disorders, such as convulsion and epilepsy

• The patient has a severe hepatic dysfunction

• The patient has a severe cardiac dysfunction

• The patient has cardiac arrhythmia or congenital or sporadic long QTc syndrome. Or the patient is treated with a drug reported to prolong QTc interval

• The patient has a moderate or severe renal dysfunction

• Women with confirmed or suspected pregnancy or breast-feeding women

• Patients judged to be ineligible by the investigator for any other reasons

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Kanto, Region		Japan
2		Seoul		Korea, Republic of
3		Singapore		Singapore

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Yoshitaka Kotobuki, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Jul 15, 2016
• Statistical Analysis Plan - Mar 3, 2017

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02473393
• Other Study ID Numbers: 341-13-002; JapicCTI-152937
• First Posted: Jun 16, 2015
• Last Update Posted: Mar 24, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Enteritis

Study Results

Participant Flow

Recruitment Details

This trial was performed as a global trial in Japan, Republic of Korea, and Singapore.

Pre-assignment Detail

Subjects with bacterial enteritis were divided into 2 groups, a Clostridium difficile infection (CDI) group for subjects with bacterial enteritis associated with C. difficile infection and an enteric infection (EI) group for subjects with bacterial enteritis for which the causative pathogen was Salmonella, Campylobacter, or pathogenic E. coli. Only one dosage (100 mg) of OPS-2071 was administered to CDI subjects and 3 dosages (100, 50, and 200 mg) were administered to EI subjects.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Period Title: Overall Study
STARTED	5	12	13	13
COMPLETED	5	12	11	12
NOT COMPLETED	0	0	2	1

Baseline Characteristics

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)	Total
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	Total of all reporting groups
Overall Participants	5	12	12	12	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	11 91.7%	11 91.7%	12 100%	37 90.2%
>=65 years	2 40%	1 8.3%	1 8.3%	0 0%	4 9.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (24.52)	36.0 (15.78)	36.3 (16.51)	35.6 (12.41)	39.4 (18.22)
Sex: Female, Male (Count of Participants)
Female	3 60%	5 41.7%	7 58.3%	5 41.7%	20 48.8%
Male	2 40%	7 58.3%	5 41.7%	7 58.3%	21 51.2%
Race/Ethnicity, Customized (Count of Participants)
Japanese	4 80%	12 100%	10 83.3%	10 83.3%	36 87.8%
Korean	0 0%	0 0%	2 16.7%	1 8.3%	3 7.3%
Singaporean	0 0%	0 0%	0 0%	0 0%	0 0%
Others	1 20%	0 0%	0 0%	1 8.3%	2 4.9%
Region of Enrollment (Count of Participants)
South Korea	0 0%	0 0%	2 16.7%	0 0%	2 4.9%
Singapore	1 20%	0 0%	0 0%	0 0%	1 2.4%
Japan	4 80%	12 100%	10 83.3%	12 100%	38 92.7%

Outcome Measures

1. Primary Outcome

Title	Bacterial Elimination Rate (BER) in the CDI and EI Groups
Description	Judged according to the assessment criteria for the bacterial strain isolated as the causative pathogen based on the data from the microbiological examination. Analysis was performed by disease group and by dose, and by minimum inhibitory concentration (MIC) values of OPS-2071 for each of the causative strains (Enterotoxigenic E. coli, Enteroaggregative E. coli, Campylobacter sp., C. jejuni, S. aureus, K. oxytoca, and C. perfringens for the EI group). Data were shown as all strains total. Concerning microbiological outcome by causative strain, bacteria elimination rate (BER) and its 95% confidence interval (CI) were calculated. The BER was the proportion of causative strains assessed as either "Excellent" or "Good" except for those assessed as "unknown/indeterminate".
Time Frame	CDI group: screening, Day 4 and Day 11 (end of treatment), EI group: screening, Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

Microbiological per Protocol Set (MPPS) comprised those subjects in the FAS for whom the causative pathogen was identified and for whom microbiological outcome was assessed as "Excellent", "Good", or "Poor" , excluding subjects for whom microbiological outcome was assessed as "unknown/indeterminate".

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	2	9	9	7
Number (95% Confidence Interval) [percentage of participants]	100.0 2000%	72.7 605.8%	90.0 750%	87.5 729.2%

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of OPS-2071 on Day 4
Description	We measured OPS-2071 concentration in plasma and evaluated Cmax of OPS-2071 in plasma.
Time Frame	Inpatient: 1h, 2h, and 4h after morning administration

Outcome Measure Data

Analysis Population Description

Pharmacokinetics Analysis Set (PKS) comprised subjects in whom plasma drug concentration had been measured at least once.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	1	2	2	2
Mean (Full Range) [µg/L]	64	29.2	42.4	81.9

3. Primary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of OPS-2071 on Day 4
Description	We measured OPS-2071 concentration in plasma and evaluated tmax of OPS-2071 in plasma.
Time Frame	1h, 2h, and 4h after morning administration

Outcome Measure Data

Analysis Population Description

Pharmacokinetics Analysis Set (PKS) comprised subjects in whom plasma drug concentration had been measured at least once.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	1	2	2	2
Mean (Full Range) [h]	4.15	1.98	4.08	2.42

4. Secondary Outcome

Title	The Recurrence Rate of CDI After Multiple Doses of OPS-2071 (for CDI Group Only)
Description	CDI recurrence rate at follow-up (Day 38) or withdrawal was calculated. CDI recurrence rate was the proportion of the subjects judged as "recurrent" against evaluable subjects, except for those with missing data.
Time Frame	Day 38

Outcome Measure Data

Analysis Population Description

Clinical per protocol set (CPPS) comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed. Analysis was performed by dose in the proportion of subjects judged as "clinical cure" at end of treatment (EOT) in the CPPS.

Arm/Group Title	CDI Group
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.
Measure Participants	4
Number [percentage of participants]	0.0 0%

5. Secondary Outcome

Title	The Time to Resolution of Diarrhea After Multiple Doses of OPS-2071
Description	The time from the start of dosing until the first formed stool (except in cases where liquid or unformed stools recurred) was evaluated as time to resolution of diarrhea. If formed stool has not been observed, then the subject will be handled as missing data.
Time Frame	CDI group: Day 4, Day 11 (end of treatment) and Day 38, EI group: Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

CPPS comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	3	10	9	9
Mean (Standard Deviation) [days]	3.7 (1.53)	4.3 (1.34)	4.4 (2.01)	4.6 (1.42)

6. Secondary Outcome

Title	Stool Frequency Per Day After Multiple Doses of OPS-2071
Description	Under each disease group, the improvement of clinical symptoms (stool frequency/day) were assessed.
Time Frame	CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

CPPS comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	4	10	10	12
Screening	5.3 (3.30)	7.3 (2.91)	7.1 (2.77)	9.2 (4.28)
Day 4	1.5 (0.58)	2.9 (1.52)	1.4 (0.97)	2.7 (2.74)
Day 8	2.0 (1.41)	1.7 (0.67)	2.6 (1.93)
Day 11	2.3 (0.96)
Day 38	1.3 (0.58)

7. Secondary Outcome

Title	Number of Subjects With Formed Stool, Liquid or Unformed Stool, and Bloody Stool After Multiple Doses of OPS-2071
Description	Under each disease group, the improvement of clinical symptoms ((i.e. formed stool, liquid or unformed stool [3 and more times], and presence of bloody stool) were assessed.
Time Frame	CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

CPPS comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	4	10	10	12
Formed stool at Screening	0 0%	0 0%	0 0%	0 0%
Formed stool on Day 4	2 40%	7 58.3%	3 25%	5 41.7%
Formed stool on Day 8	7 140%	9 75%	8 66.7%
Formed stool on Day 11	1 20%
Formed stool on Day 38	2 40%
Liquid or unformed stool at Screening	4 80%	10 83.3%	10 83.3%	12 100%
Liquid or unformed stool on Day 4	0 0%	1 8.3%	0 0%	3 25%
Liquid or unformed stool on Day 8	0 0%	0 0%	2 16.7%
Liquid or unformed stool on Day 11	2 40%
Liquid or unformed stool on Day 38	0 0%
Bloody stool at Screening	0 0%	2 16.7%	3 25%	2 16.7%
Bloody stool on Day 4	0 0%	0 0%	0 0%	0 0%
Bloody stool on Day 8	0 0%	0 0%	0 0%
Bloody stool on Day 11	0 0%
Bloody stool on Day 38	0 0%

8. Secondary Outcome

Title	Number of Subjects With Abdominal Pain, Nausea, and Vomiting After Multiple Doses of OPS-2071
Description	Under each disease group, he improvement of clinical symptoms (i.e. presence of abdominal pain, nausea, and vomiting) were assessed.
Time Frame	CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

CPPS comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	4	10	10	12
Abdominal pain at Screening	2 40%	10 83.3%	10 83.3%	12 100%
Abdominal pain on Day 4	1 20%	4 33.3%	3 25%	5 41.7%
Abdominal pain on Day 8	1 20%	0 0%	2 16.7%
Abdominal pain on Day 11	0 0%
Abdominal pain on Day 38	0 0%
Nausea at Screening	1 20%	6 50%	7 58.3%	2 16.7%
Nausea on Day 4	0 0%	0 0%	0 0%	0 0%
Nausea on Day 8	0 0%	0 0%	0 0%
Nausea on Day 11	0 0%
Nausea on Day 38	0 0%
Vomiting at Screening	0 0%	2 16.7%	3 25%	0 0%
Vomiting on Day 4	0 0%	0 0%	0 0%	0 0%
Vomiting on Day 8	0 0%	1 8.3%	0 0%
Vomiting on Day 11	0 0%
Vomiting on Day 38	0 0%

9. Secondary Outcome

Title	Clinical Response Rate (CRR) in the CDI and EI Groups
Description	The CRR and 95% CI at each evaluation time point were calculated. The CRR was calculated as the proportion of the subjects judged as "clinical cure" or "clinical improvement" against evaluable subjects, except for those with missing data.
Time Frame	CDI group: Day 4 and Day 11 (end of treatment), EI group: Day 4 and Day 8 (end of treatment)

Outcome Measure Data

Analysis Population Description

CPPS comprised those subjects in the FAS for whom all scheduled examinations at all specified observation time points up until end of treatment or withdrawal had been performed.

Arm/Group Title	CDI Group	EI Group (50 mg)	EI Group (100 mg)	EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.	OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
Measure Participants	4	10	10	12
Day 4	100.0 2000%	100.0 833.3%	100.0 833.3%	100.0 833.3%
End of treatment	100.0 2000%	100.0 833.3%	90.0 750%	100.0 833.3%

Adverse Events

Time Frame	From the start day of IMP administration up to Day 38
Adverse Event Reporting Description	Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. All subjects receiving at least 1 dose of IMP were included in the safety set.
Arm/Group Title	CDI Group		EI Group (50 mg)		EI Group (100 mg)		EI Group (200 mg)
Arm/Group Description	OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 10 days.		OPS-2071 was orally administered at a dose of 25 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.		OPS-2071 was orally administered at a dose of 50 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.		OPS-2071 was orally administered at a dose of 100 mg twice daily in the morning and evening for 7 days. The administration was started with the 100 mg group, and the safety and efficacy during the treatment period were to be assessed by the Data Review Committee. If the 100 mg group had no safety concerns and the efficacy was assessed "effective," 10 subjects each who were not in the 100 mg group were to be randomized to the 200 mg or 50 mg group, and the 2 groups were to be treated in parallel. If the 100 mg group had no safety concerns and the efficacy was assessed "not effective," 10 subjects who were not in the 100 mg group were to be allocated to the 200 mg group as the next step.
All Cause Mortality
	CDI Group		EI Group (50 mg)		EI Group (100 mg)		EI Group (200 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Serious Adverse Events
	CDI Group		EI Group (50 mg)		EI Group (100 mg)		EI Group (200 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
General disorders
Pyrexia	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	CDI Group		EI Group (50 mg)		EI Group (100 mg)		EI Group (200 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		4/12 (33.3%)		8/13 (61.5%)		4/12 (33.3%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Eosinophilia	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		1/12 (8.3%)
Cardiac disorders
Cardiac failure	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Nausea	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
Vomiting	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
General disorders
Malaise	0/5 (0%)		1/12 (8.3%)		0/13 (0%)		0/12 (0%)
Pyrexia	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Hepatobiliary disorders
Hepatic steatosis	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Infections and infestations
Herpes zoster	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Pneumonia	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Urinary tract infection	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Investigations
Alanine aminotransferase increased	0/5 (0%)		2/12 (16.7%)		0/13 (0%)		1/12 (8.3%)
Hepatic enzyme increased	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Dehydration	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Hyperglycaemia	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Hypertriglyceridaemia	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Hypoglycaemia	0/5 (0%)		1/12 (8.3%)		0/13 (0%)		0/12 (0%)
Hypokalaemia	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate	1/5 (20%)		0/12 (0%)		0/13 (0%)		0/12 (0%)
Musculoskeletal stiffness	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Neck pain	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
Nervous system disorders
Headache	0/5 (0%)		1/12 (8.3%)		2/13 (15.4%)		0/12 (0%)
Intercostal neuralgia	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
Somnolence	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)
Psychiatric disorders
Insomnia	0/5 (0%)		0/12 (0%)		0/13 (0%)		1/12 (8.3%)
Reproductive system and breast disorders
Dysmenorrhoea	0/5 (0%)		1/12 (8.3%)		0/13 (0%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		1/12 (8.3%)		0/13 (0%)		0/12 (0%)
Epistaxis	0/5 (0%)		0/12 (0%)		1/13 (7.7%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.