Secretory Diarrhea Clinical Trial
Official 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
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment