Secretory Diarrhea Clinical Trial
— POCOfficial title:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Two-Part Trial to Evaluate the Efficacy, Safety, and Tolerability of iOWH032 in the Treatment of Acute Dehydrating Diarrhea in Adult and Pediatric Patients With Cholera
| Verified date | April 2014 |
| Source | PATH |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
The primary hypothesis is that administration of iOWH032 to adult and pediatric males and females with acute cholera due to V. cholerae O1 reduces stool output in the first 24 hours significantly more than does the current standard of care.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | May 2016 |
| Est. primary completion date | January 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 5 Years to 55 Years |
| Eligibility |
Approximately 170 adult (male and female) patients must be enrolled to ensure that 96
patients (48 active and 48 placebo) are evaluable in Part A. In Part B, approximately 156
pediatric patients will be enrolled to ensure that 120 pediatric patients (60 active and
60 placebo) are evaluable for the analysis of 24 hour stool output, the primary outcome
measure. PART A - ADULTS ***Inclusion Criteria*** A patient will be considered eligible for participation in the study if the following inclusion criteria are satisfied on admission (Day 1) to the Dhaka Hospital of icddr,b: - Adults aged 18 years to 55 years - Duration of illness: History of acute watery diarrhea of less than 24 hours' duration without fever or visible blood in feces - Clinical signs and symptoms of severe dehydration (>10% loss of body weight based on rehydration weight) - Stool RDT and/or stool DF microscopy demonstrating presence of V. cholerae - Must have a purging rate greater than/equal to 20 mL/kg (5 mL/kg/h) during the initial 4- to 6-hour screening/observation period, and signs of clinical dehydration must be corrected - Written informed consent for participation in the study (see Section 6.1.2 for details of the consent process) - Negative urine pregnancy test for all female patients - Nonpregnant and nonlactating females of childbearing potential agree to either abstain from sex or use double barrier contraception (2 contraceptive methods at a time) during the study and until 1 month after the last dose of study drug ***Exclusion Criteria*** A patient with any of the following criteria at screening for study enrollment will not qualify for the study: - Received antidiarrheal medication (eg, loperamide, diphenoxylate) within 7 days before screening - Abnormal ECG findings, with the exception of sinus tachycardia, premature atrial contractions, or ECG intervals within normal limits for sinus rate - Use of drugs metabolized predominantly via CYP2C9 within 7 days before screening (see Section 5.7) - Concomitant infection requiring antimicrobial therapy other than the study drug that may interfere with the evaluation of either the efficacy or safety of the study drug - Patients unwilling or unable to take part in this study or refusing to sign informed consent (patients who participate on the basis of proxy consent will be re-consented at the end of the screening/observation period; those refusing consent at that time will be excluded from further study participation) - Patients previously enrolled in this or any other investigational study within the past 30 days PART B - PEDIATRIC ***Inclusion Criteria*** A patient will be considered eligible for participation in the study if the following inclusion criteria are satisfied on admission (Day 1) to the Clinical Research Ward (CRW) of Dhaka Hospital: - Pediatric population aged = 5 years to < 18 years of age - Duration of illness: History of acute watery diarrhea of less than 24 hours' duration without fever or visible blood in feces - Clinical signs and symptoms of severe dehydration (>10% loss of body weight based on rehydration weight) - Stool RDT and/or stool DF microscopy demonstrating presence of V. cholerae - Must have a purging rate =5 mL/kg/h average during the initial 4- to 6-hour screening/observation period and signs of clinical dehydration must be corrected - Parental consent for all pediatric patients participating in the study and written informed assent for children aged 11-17 years (see Section 6.1.2 for details of the consent process) - Negative urine pregnancy test for female postmenarchal patients - Nonpregnant and nonlactating females of childbearing potential agree to either abstain from sex or use double-barrier contraception (2 contraceptive methods at a time) during the study and until 1 month after the last dose of study drug ***Exclusion Criteria*** A patient with any of the following criteria at screening for study enrollment will not qualify for the study: - Received antidiarrheal medication (eg, loperamide, diphenoxylate) within 7 days before screening - Abnormal ECG findings, with the exception of sinus tachycardia, premature atrial contractions, or ECG intervals within normal limits for sinus rate - Use of drugs metabolized predominantly via CYP2C9 (see Section 5.7) within 7 days before screening - Concomitant infection requiring antimicrobial therapy other than the study drug that may interfere with evaluation of either the efficacy or safety of the study drug - Children or parents/guardians unwilling or unable to take part in this study or refusing to sign informed assent/consent; applicable patients who participate on the basis of proxy assent/consent will be re-assented at the end of the screening/observation period; those refusing assent/consent at that time will be excluded from further study participation - Patients previously enrolled in this or any other investigational study with the past 30 days |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Bangladesh | International Centre for Diarrhoeal Disease Research, Bangladesh | Dhaka |
| Lead Sponsor | Collaborator |
|---|---|
| PATH | Bill and Melinda Gates Foundation |
Bangladesh,
Bardhan PK, Khan WA, Ahmed S, Salam MA, Saha D, Golman D, et al. Evaluation of safety and efficacy of a novel anti-secretory anti-diarrheal agent Crofelemer (NP-303), in combination with a single oral dose of azithromycin for the treatment of acute dehydrating diarrhea caused by Vibrio cholera cholera and other Bacterial Infections: 43rd US-Japan Cooperative Medical Science Program, Kyoto, Japan, November 21, 2008.
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Verkman AS, Galietta LJ. Chloride channels as drug targets. Nat Rev Drug Discov. 2009 Feb;8(2):153-71. doi: 10.1038/nrd2780. Epub 2008 Jan 19. Review. — View Citation
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Safety | The safety and tolerability endpoints for this study are AEs, clinical laboratory values, physical examination results, vital signs, and ECG findings. All patients in Part A and B of the study who receive study drug will be included in the safety analysis. Acceptability of the iOWH032 dispersible tablet or suspension formulation will be evaluated in Part B of the study (pediatric patients). |
Duration of Study | Yes |
| Primary | Output (mL/kg of body weight) of unformed stools (composite) | The primary objectives of the study are as follows: To evaluate the efficacy of iOWH032 in adults with cholera, as measured by unformed stool output in the first 24 hours after administration (Part A) To determine an effective dose and dosing regimen of iOWH032 in children with cholera (Part A) To evaluate the efficacy of iOWH032 at this recommended dose and dosing regimen in children with cholera (Part B) |
First 24-hour period following randomization | Yes |
| Secondary | Total stool output (mL/kg body weight) (composite) | Total stool output (mL/kg body weight) from randomization until the resolution of diarrhea, or until 3 days (72 hours post-dose) after administration of the first dose of study drug, whichever is sooner Time to resolution of diarrhea Incidence of diarrhea resolution within 48 hours and within 72 hours from the time of administration of the first dose of study drug Intake of ORS solution and plain water in mL/kg from time of randomization through the last unformed stool or until 3 days (72 hours) after administration of the first dose of study drug, whichever is sooner Requirement for unscheduled IV rehydration therapy (mL/kg) after randomization Sodium, potassium, chloride, cAMP, parent drug, and metabolite concentrations, all in the stool Sensitivity, specificity, positive and negative predictive values, and accuracy of stool DF and RDT in the diagnosis of cholera, and the impact of antibiotic therapy on DF and RDT |
From randomization until the resolution of diarrhea, or until 3 days (72 hours post-dose) after administration of the first dose of study drug, whichever is sooner | Yes |