Efficacy of iOWH032 in Dehydrating Cholera
- Registration Number
- NCT02111304
- Lead Sponsor
- PATH
- Brief Summary
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.
- Detailed Description
This is a Phase 2, randomized, double-blind, placebo-controlled study of iOWH032 in adult patients (Part A) and then pediatric patients (Part B) with acute watery diarrhea of less than 24 hours' duration due to cholera. All subjects will be treated with standard of care (IV rehydration fluids, ORS, and azithromycin less than/equal to1 g po) in addition to study drug (iOWH032 active drug or placebo). Patients will be admitted, undergo a 4- to 6-hour screening/observation period, be randomized in the study and treated with study drug (active or placebo) for up to 3 days (ie, up to 9 doses), with a follow-up visit on Day 7.
In Part A, approximately 170 adult patients with severe dehydrating diarrhea due to cholera will be enrolled and randomized 1:1 to receive iOWH032 500 mg or placebo TID for up to 3 days. Following completion of Part A, the data and safety monitoring board (DSMB) will review the unblinded data to assess safety and efficacy and conduct a futility analysis prior to proceeding to Part B.
Following the DSMB recommendation of dose and dosing schedule for pediatric patients, Part B will be initiated. Approximately 156 pediatric patients with severe dehydrating diarrhea due to cholera will be enrolled and randomized 1:1 to receive iOWH032 or placebo at the recommended dose and dosing regimen.
The primary efficacy population for Parts A and B will consist of patients who tolerate the first 3 doses of study drug (0, 8, and 16 hours post-randomization) without vomiting and whose diagnosis is subsequently confirmed by a positive culture for V. cholerae O1.
The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) Ethics Committee and Western Institutional Review Board (WIRB) will be informed of any serious adverse event (SAE). Occurrence of 2 or more drug-related SAEs within a group of 10 patients (20% of cumulative completed patients in the treatment group) in Part A or Part B will result in unblinding of those patients and review by the DSMB. The study can be halted, discontinued, or amended according to the recommendations of the icddr,b DSMB.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B (Pediatric) iOWH032 Following completion of Part A, the data and safety monitoring board (DSMB) will review the unblinded data to assess safety and efficacy and conduct a futility analysis prior to proceeding to Part B. Following the DSMB recommendation of dose and dosing schedule for pediatric patients, Part B will be initiated. Approximately 156 pediatric patients with severe dehydrating diarrhea due to cholera will be enrolled and randomized 1:1 to receive iOWH032 or placebo at the recommended dose and dosing regimen. Part A (Adults) iOWH032 In Part A, approximately 170 adult patients with severe dehydrating diarrhea due to cholera will be enrolled and randomized 1:1 to receive iOWH032 500 mg or placebo TID for up to 3 days
- Primary Outcome Measures
Name Time Method Output (mL/kg of body weight) of unformed stools (composite) First 24-hour period following randomization 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)
- Secondary Outcome Measures
Name Time Method Total stool output (mL/kg body weight) (composite) 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 * 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
Trial Locations
- Locations (1)
International Centre for Diarrhoeal Disease Research, Bangladesh
🇧🇩Dhaka, Bangladesh