Efficacy of iOWH032 in Dehydrating Cholera

NCT02111304 | Withdrawn Phase 2 DMC

• 1 other identifier: POC Study (DDP CFT PO 202)
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Secretory Diarrhea

Keywords

cholera; diarrhea; secretory diarrhea; ORS; V. cholerae O1; iOWH032; children; pharmacokinetic; Bangladesh

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Other Outcomes (1)

• Safety

  Duration of Study

Study Arms (2)

Part A (Adults)

ACTIVE COMPARATOR

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

Drug: iOWH032

Part B (Pediatric)

ACTIVE COMPARATOR

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.

Drug: iOWH032

Interventions

iOWH032 DRUG

Part A (Adults); Part B (Pediatric)

Eligibility Criteria

• Age: 5 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• PATH: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, 1212, Bangladesh

Location

Related Publications (14)

• 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.

  BACKGROUND

• Boschi-Pinto C, Lanata CF, Black RE. The global burden of childhood diarrhea. Matern Child Health. 2009;3: 225-243.

  BACKGROUND

• Cystic Fibrosis Mutation Database, 2009 [online] Available at: http://www.genet.sickkids.on.ca/cftr/app

  BACKGROUND

• Khan WA, Saha D, Rahman A, Salam MA, Bogaerts J, Bennish ML. Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial. Lancet. 2002 Nov 30;360(9347):1722-7. doi: 10.1016/S0140-6736(02)11680-1.

  PMID: 12480424 BACKGROUND

• Muanprasat C, Sonawane ND, Salinas D, Taddei A, Galietta LJ, Verkman AS. Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J Gen Physiol. 2004 Aug;124(2):125-37. doi: 10.1085/jgp.200409059.

  PMID: 15277574 BACKGROUND

• Raghupathy P, Ramakrishna BS, Oommen SP, Ahmed MS, Priyaa G, Dziura J, Young GP, Binder HJ. Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea. J Pediatr Gastroenterol Nutr. 2006 Apr;42(4):362-8. doi: 10.1097/01.mpg.0000214163.83316.41.

  PMID: 16641573 BACKGROUND

• Ram PK, Choi M, Blum LS, Wamae AW, Mintz ED, Bartlett AV. Declines in case management of diarrhoea among children less than five years old. Bull World Health Organ. 2008 Mar;86(3):E-F. doi: 10.2471/blt.07.041384. No abstract available.

  PMID: 18368194 BACKGROUND

• Saha D, Karim MM, Khan WA, Ahmed S, Salam MA, Bennish ML. Single-dose azithromycin for the treatment of cholera in adults. N Engl J Med. 2006 Jun 8;354(23):2452-62. doi: 10.1056/NEJMoa054493.

  PMID: 16760445 BACKGROUND

• StataCorp. POWERCAL: Stata module to perform general power and sample size calculations. http://ideas.repec.org/c/boc/bocode/s422401.html. 2013. Stata Statistical Software: Release 13. StataCorp LP, College Station, TX.

  BACKGROUND

• United Nations Children's Fund (UNICEF) and World Health Organization (WHO). Diarrhoea: Why children are still dying and what can be done. 2009. New York and Geneva.

  BACKGROUND

• 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.

  PMID: 19153558 BACKGROUND

• Victora CG, Bryce J, Fontaine O, Monasch R. Reducing deaths from diarrhoea through oral rehydration therapy. Bull World Health Organ. 2000;78(10):1246-55.

  PMID: 11100619 BACKGROUND

• World Health Organization. The rational use of drugs in the management of acute diarrhoea in children. WHO, Geneva, 1990.

  BACKGROUND

• Zhou Z, Wang X, Liu HY, Zou X, Li M, Hwang TC. The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics. J Gen Physiol. 2006 Oct;128(4):413-22. doi: 10.1085/jgp.200609622. Epub 2006 Sep 11.

  PMID: 16966475 BACKGROUND

MeSH Terms

Conditions

Cholera; Diarrhea

Interventions

IOWH-032

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Wasif A Khan, MBBS/MHS

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

• KATM Ehsanul Huq, MBBS/DTM

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 11, 2014
• Study Start: June 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: May 1, 2016
• Last Updated: September 26, 2014

Record last verified: 2014-04

Locations

BA (1)