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

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

Conditions
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Bacterial Enteritis

Intervention / Treatment
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* Drug: OPS-2071 tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial Elimination Rate (BER) in the CDI and EI Groups | 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. | CDI group: screening, Day 4 and Day 11 (end of treatment), EI group: screening, Day 4 and Day 8 (end of treatment) | 
| Maximum Plasma Concentration (Cmax) of OPS-2071 on Day 4 | We measured OPS-2071 concentration in plasma and evaluated Cmax of OPS-2071 in plasma. | Inpatient: 1h, 2h, and 4h after morning administration | 
| Time to Maximum Plasma Concentration (Tmax) of OPS-2071 on Day 4 | We measured OPS-2071 concentration in plasma and evaluated tmax of OPS-2071 in plasma. | 1h, 2h, and 4h after morning administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Recurrence Rate of CDI After Multiple Doses of OPS-2071 (for CDI Group Only) | 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. | Day 38 | 
| The Time to Resolution of Diarrhea After Multiple Doses of OPS-2071 | 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. | CDI group: Day 4, Day 11 (end of treatment) and Day 38, EI group: Day 4 and Day 8 (end of treatment) | 
| Stool Frequency Per Day After Multiple Doses of OPS-2071 | Under each disease group, the improvement of clinical symptoms (stool frequency/day) were assessed. | CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment) | 
| Number of Subjects With Formed Stool, Liquid or Unformed Stool, and Bloody Stool After Multiple Doses of OPS-2071 | 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. | CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment) | 
| Number of Subjects With Abdominal Pain, Nausea, and Vomiting After Multiple Doses of OPS-2071 | Under each disease group, he improvement of clinical symptoms (i.e. presence of abdominal pain, nausea, and vomiting) were assessed. | CDI group: screening, Day 4, Day 11 (end of treatment) and Day 38, EI group: screening, Day 4 and Day 8 (end of treatment) | 
| Clinical Response Rate (CRR) in the CDI and EI Groups | 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. | CDI group: Day 4 and Day 11 (end of treatment), EI group: Day 4 and Day 8 (end of treatment) |