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

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

Study Overview

• Status: Completed
• Conditions: Bacterial Enteritis
• Intervention / Treatment: Drug: OPS-2071 tablet

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kanto, Region, Japan
• Korea, Republic of
  • Seoul, Korea, Republic of
• Singapore
  • Singapore, Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2015
• Primary Completion (Actual): March 14, 2017
• Study Completion (Actual): March 14, 2017

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enteritis
• Other Study ID Numbers: 341-13-002; JapicCTI-152937 (Other Identifier: Japic)