A Comparison of Three Medications to Treat Diarrhea in Adults.

A Randomized, Parallel Group Comparison of Loperamide/Simeticone Caplet, Loperamide/Simeticone Chewable Tablet (IMODIUM® PLUS) and a Probiotic (Saccharomyces Boulardii) in the Treatment of Acute Diarrhea in Adults

A comparison of three medications to treat diarrhea in adults.

Study Overview

• Status: Completed
• Conditions: Diarrhea
• Intervention / Treatment: Drug: Loperamide/simeticone 2 mg/125 mg caplets; Drug: Loperamide/simeticone 2 mg/125 mg chewable tablets; Drug: Probiotic Saccharomyces boulardii 250 mg capsules

Detailed Description

This single (investigator) blind, randomized, 3-arm, parallel-group study design was selected to show non-inferiority of loperamide/simeticone caplets compared to chewable tablets in a heterogeneous subject population aiming at validity of results and reducing bias. The study will also compare the loperamide/simeticone combinations versus a probiotic (Saccharomyces boulardii) in the treatment of acute diarrhea in adults. Probiotics have been used for acute infectious diarrhea to reduce the duration and severity of the illness.

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Goa, India, 403004
    • Manipal Goa Hospital
  • Goa, India, 403527
    • Vrundavan Hospital & Research Centre
• Mexico
  • Baja California Sur
    • San José del Cabo, Baja California Sur, Mexico, 22447
      • North West Medical
  • Guanuajuato
    • San Miguel de Allende, Guanuajuato, Mexico, 37700
      • Dr. Maxwell´s Clinic
  • Jalisco
    • Puerto Vallarta, Jalisco, Mexico, 48300
      • Hospital Amerimed Puerto Vallarta
    • Puerto Vallarta, Jalisco, Mexico, 48300
      • Servicios Medicos de la Bahia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female at least 18 years of age
• Acute diarrhea illness with symptoms onset within 48 hours of study entry
• Minimum of 3 unformed stools in 24 hours before study entry
• Most recent stool is unformed
• Abdominal discomfort/wind (intensity mild to severe) within 4 hours of study entry
• Women of childbearing potential must have a negative pregnancy test at screening
• Willing to adhere to the prohibitions and restrictions specified in this protocol
• Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Requiring hospital admission, parenteral hydration or antibiotic therapy Axillary temperature >38.2°C or oral temperature >38.6°C
• History or clinical evidence of gross blood or pus in stool in current illness
• Signs or symptoms of orthostatic hypotension
• Unable to take medication and fluids by mouth
• History of chronic gastrointestinal disease, hepatic or renal insufficiency, or other significant medical condition that could be aggravated by untreated acute diarrhea
• Immunodeficiency (e.g. those with acquired immunodeficiency syndrome [AIDS] or known human immunodeficiency virus [HIV] infection, or undergoing chemotherapy or radiotherapy)
• Intake of antibiotics, oral antifungals, quinidine or ritonavir within 7 days, antidiarrhoeal, promotility drugs (e.g., metoclopramide, domperidone), antiflatulents (e.g., simeticone, activated charcoal) or probiotics or bismuth salts within 48 hours, or any analgesic within 6 hours prior to study entry Hypersensitivity to loperamide, yeast, or any component of study formulations
• Pregnant or breast-feeding
• Unable to comply with the protocol requirements and schedule
• Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study
• Use of opiates (as 'recreational' drugs and as painkillers)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Loperamide/simeticone Caplets; Drug (including placebo)	Drug: Loperamide/simeticone 2 mg/125 mg caplets; Oral, 2 caplets taken initially at investigator site followed by one caplet after each unformed stool, maximum 4 caplets in a 24 hour period for a maximum of 48 hours (per product label); Other Names: Imodium® Plus Caplet
Active Comparator: Loperamide/simeticone Chewable Tablets; Drug (including placebo)	Drug: Loperamide/simeticone 2 mg/125 mg chewable tablets; Oral, 2 chewable tablets taken initially at the site followed by one chewable tablet after each unformed stool, maximum 4 chewable tablets in a 24 hour period for a maximum of 48 hours (per product label); Other Names: Imodium® Plus Chewable tablet
Active Comparator: Probiotic Capsules; Drug (including placebo)	Drug: Probiotic Saccharomyces boulardii 250 mg capsules; Oral, 1 capsule twice a day, maximum 2 capsules in a 24 hour period for a maximum of 5 days (per product label); Other Names: Perenterol® Forte 250mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of unformed stools	0-24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of unformed stools	0-12, 12-24, 24-36, 36-48 hours
Time to last unformed stool	Throughout duration of the study
Time to complete relief of abdominal discomfort	Throughout duration of the study
Time to complete relief of diarrhea	Throughout duration of the study
Proportion of subjects with complete relief of diarrhea	4, 8, 12, 24 and 48 hours
Gas-related abdominal discomfort ratings - change from baseline at subsequent time points	Throughout duration of the study
Proportions of subjects with complete well-being	at 12, 24 and 48 hours.
Subject's evaluation of treatment effectiveness for overall illness relief, diarrhea relief and abdominal discomfort relief	Throughout duration of the study
Number of loperamide/simeticone 2 mg/125 mg caplets or chewable tablets or probiotic (Saccharomyces boulardii) 250 mg capsules used during the study	Throughout duration of the study
Frequency of complete well-being following diarrhea illness	at 7 days follow up
Stool frequency	at 7 days follow up
Frequency of diarrhea relapse	at 7 days follow up
Safety Assessments will consist of monitoring and recording all non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs), their frequency, severity, seriousness, and relationship to the investigational product.	throughout duration of the study (+ 30 days for spontaneously-reported SAEs)

Collaborators and Investigators

• Sponsor: McNeil AB

Publications and helpful links

General Publications

• Cottrell J, Koenig K, Perfekt R, Hofmann R; Loperamide-Simethicone Acute Diarrhoea Study Team. Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial. Drugs R D. 2015 Dec;15(4):363-73. doi: 10.1007/s40268-015-0111-y.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: December 9, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Estimate): July 10, 2012
• Last Update Submitted That Met QC Criteria: July 6, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Antidiarrheals
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Dermatologic Agents; Antifoaming Agents; Emollients; Simethicone; Loperamide; Antidiarrheals
• Other Study ID Numbers: LOPDIR4002