Efficacy of Diosmectite (Smecta®) in the Symptomatic Treatment of Acute Diarrhoea in Adults

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate that diosmectite efficacy is superior to placebo regarding time to recovery of an acute diarrhoea episode presumed of infectious origin in adult subjects.

Official Title
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Efficacy of Diosmectite (Smecta®) in the Symptomatic Treatment of Acute Diarrhoea in Adults. A Multicentre, Randomized, Double Blind Placebo Controlled, Parallel, Groups Study

Conditions
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Acute Diarrhoea

Intervention / Treatment
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* Drug: Smecta
* Drug: Smecta placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent prior to any study related procedures Male or female subject (outpatient) legally considered as an adult (age of majority). In Czech Republic, the upper limit of age will be 70 years inclusive. In Egypt, the upper limit of age will be 60 years inclusive. Subject has a diagnosis of acute diarrhoea presumed of infectious origin, defined as the passage of 3 or more unformed loose or watery stools (rated according to the Bristol scale) per day within the last 48 hours without associated alarm symptoms Subject has, usually, normal bowel habits (Rome III criteria), i.e. at least 3 stools per week and no more than 3 stools per day Subject must be willing and able to comply with study restrictions and willing to return to the clinic for the follow up evaluation(s) as specified in the protocol. Exclusion criteria related to the acute diarrhoea episode: At least one of the following alarm symptoms Bloody diarrhoea*, pus in the stools*, fever ≥38°C*, moderate or severe dehydration according to World Health Organisation (WHO) definition, requiring intravenous (IV) rehydration*, repeated vomiting*, persistent abdominal pain* *These symptoms are considered as alarm symptoms other episode of acute watery diarrhoea within the previous 30 days, persistent diarrhoea, defined as acutely starting episode of diarrhoea lasting more than 14 days, history of chronic diarrhoea (Rome III criteria); i.e. 3 or more loose or watery stools per day for at least 12 weeks, consecutive or not, in the preceding 12 months, traveller's diarrhoea defined as a diarrhoeal episode due to contamination experienced by subjects having travelled in at risk countries, or coming from abroad and experiencing locally an acute diarrhoea episode, occurring usually within the first 2 weeks of the stay in a foreign environment. Exclusion criteria related to drugs: Diarrhoea suspected to be induced by drug for example: antibiotic therapy, including Clostridium difficile-induced diarrhoea, within 1 week before entry in the study, laxative agent thyroid hormone (at a nonstabilised dosing), intake of other prohibited drugs (as specified in the protocol) anti-diarrhoeal agent intake during the last month, any subject requiring repeated intake of a drug with a narrow therapeutic margin (as specified in the protocol), history of hypersensitivity to diosmectite or its excipients or placebo components, subject likely to require treatment during the study with drugs that are not permitted by the study protocol (for example, antibiotic agent, anti-diarrhoeal agent, antiemetic drug, antispasmodic drug), use of any investigational medication within the last 30 days before entering this study, subject who previously entered in a clinical study within the past 30 days. Other digestive exclusion criteria: History of gastric or intestinal resection, vagotomy, known digestive malabsorption disease, including coeliac disease known lactose intolerance, any suspicion of abdominal surgery need, known inflammatory bowel disease. Other exclusion criteria: Known Human immunodeficiency virus (HIV) positive status, known or suspected immunosuppression, known severe renal insufficiency (including e-GFR not less than 45 mL/min) or hepatic insufficiency, known endocrine disease or Type II Diabetes Mellitus with HBA1c more than 8,5% or insulin-dependent diabetes, history of, or known current, problems with alcohol abuse and/or known drug addiction (cocaine, heroin, hashish…), previous enrolment in this study, any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Smecta<br>2 sachets, three times a day (TID), during 5 to 9 days | Drug: Smecta<br> <br> * Other names: Diosmectite Beaufour;|
| Placebo Comparator: Smecta placebo<br>2 sachets of placebo, TID, during 5 to 9 days | Drug: Smecta placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recovery | Time to recovery was defined as the time from the first study treatment intake recorded in the electronic case report form (eCRF) to the first formed stool followed by a non-watery stool, recorded in the DEB. Results are presented as median time to recovery, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered). | From randomisation (Day 1) up to Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Diarrhoea Onset to Recovery | The event of diarrhoea onset (i.e. loose or watery stool) was recorded in the eCRF and the event of recovery (i.e. first formed stool followed by a non-watery stool) was recorded in the DEB. Results are presented as median time from diarrhoea onset to recovery, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered). | From randomisation (Day 1) up to Day 9 | 
| Time From Diarrhoea Onset to First Formed Stool | The event of diarrhoea onset (i.e. loose or watery stool) was recorded in the eCRF and the event of first formed stool was recorded in the DEB. Results are presented as median time from diarrhoea onset to first formed stool, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn with no formed stool or ending the study with no formed stool were censored at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered). | From randomisation (Day 1) up to Day 9 | 
| Time From the First Study Treatment Intake to the Last Watery Stool | The event of first study treatment intake was recorded in the eCRF and the event of last watery stool was recorded in the DEB. Results are presented as median time from first study treatment intake to last watery stool, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn with no watery stool or ending the study with no watery stool were censored at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered). | From randomisation (Day 1) up to Day 9 | 
| Number of Stools, Per 12-Hour Period | Number of stools, per 12-hour period, was recorded in the DEB. | From randomisation (Day 1) up to Day 9 | 
| Number of Watery Stools, Per 12-Hour Period | Number of watery stools, per 12-hour period, was recorded in the DEB. | From randomisation (Day 1) up to Day 9 | 
| Percentage of Participants With Associated Symptoms, Per 12-Hour Period | Percentage of participants with associated symptoms (at least 1 symptom of nausea, vomiting, abdominal pain or anal irritation) per 12-hour period is presented. Nausea, vomiting, abdominal pain and anal irritation were recorded in the DEB. | From randomisation (Day 1) up to Day 9 | 
| Abdominal Pain Intensity Scores, Per 12-Hour Period | Abdominal pain intensity per 12-hour period was recorded in the DEB. Abdominal pain intensity was rated with a 5-point ordinal scale: 0 = absent, 1= mild, 2 =moderate, 3 = severe, 4= very severe. Higher scores indicate a worse outcome. The median abdominal pain intensity score for each 12-hour period is presented. | From randomisation (Day 1) up to Day 9 |