Efficacy of Diosmectite (Smecta®) in the Symptomatic Trea... | NCT02704091

NCT02704091

ID	Type	Description	Link
2015-001138-10	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Smecta	Active Comparator	2 sachets, three times a day (TID), during 5 to 9 days	Drug: Smecta
Smecta placebo	Placebo Comparator	2 sachets of placebo, TID, during 5 to 9 days	Drug: Smecta placebo

Name	Type	Description	Arm Group Labels	Other Names
Smecta	Drug		Smecta	Diosmectite Beaufour
Smecta placebo

Outcomes Module

Primary Outcomes

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 Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB.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 Outcomes

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 Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB.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).

Eligibility Module

Eligibility Criteria

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

Contacts/Locations Module

Name	Affiliation	Role
Ipsen Medical Director	Ipsen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Cabinet privé, Coopératives El MOSTAKBAL, BIRKHADEM		Algiers		16000	Algeria
CHU Beni Messous

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Diosmectite	Participants received diosmectite as 2 sachets, three times a day (TID) (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 7, 2019	Mar 19, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

The Intention-To-Treat (ITT) population included all randomised participants, analysed according to the arm to which they were randomised, except for those excluded from the analysis.

Arm/Group Information

ID	Title	Description
BG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
BG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
BG002	Total Title

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00066.0(53.7 to 71.0) OG00168.6(57.5 to 77.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary analysis tested the equality of time to recovery between the 2 treatment groups, applying the 2-sided Gehan-Wilcoxon test (α=5%).	Wilcoxon-Gehan test		=0.2524														Superiority	The following Null-hypothesis was tested: H0: λA(t) = λB (t) versus H1: λA(t) ≠ λB (t), where λ(t) represents the hazard at time t, A=diosmectite and B=placebo.

Secondary

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).

The ITT population included all randomised participants (with the exception of those excluded from the analysis), analysed according to the arm to which they were randomised. Only participants with data available were included in the analysis.

Posted

Median

95% Confidence Interval

Hours

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo

Secondary

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).

Posted

Median

Full Range

Hours

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo

Secondary

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).

The ITT population included all randomised participants (except for those excluded from the analysis), analysed according to the arm to which they were randomised.

Posted

Median

95% Confidence Interval

Hours

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Secondary

Number of Stools, Per 12-Hour Period

Number of stools, per 12-hour period, was recorded in the DEB.

Posted

Median

Full Range

Stools

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Secondary

Number of Watery Stools, Per 12-Hour Period

Number of watery stools, per 12-hour period, was recorded in the DEB.

Posted

Median

Full Range

Stools

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Secondary

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.

Posted

Number

Percentage of participants

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Secondary

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.

Posted

Median

Full Range

Scores on a scale

From randomisation (Day 1) up to Day 9

ID	Title	Description
OG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).
OG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Diosmectite	Participants received diosmectite as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).	0	430	1	430	29	430
EG001	Placebo	Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water. The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).	0	421	1	421	32	421

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Colitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0009 events9 affected430 at risk EG0019 events9 affected421 at risk
Anorectal discomfort	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0005 events5 affected430 at risk EG0013 events3 affected421 at risk
Constipation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected430 at risk EG0013 events3 affected421 at risk
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0014 events3 affected421 at risk
Proctalgia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected430 at risk EG0010 events0 affected421 at risk
Anal pruritus	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Flatulence	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0003 events3 affected430 at risk EG0017 events7 affected421 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected430 at risk EG0010 events0 affected421 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0012 events2 affected421 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0012 events2 affected421 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0011 events1 affected421 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Arthritis salmonella	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Rhinitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Urethritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected430 at risk EG0010 events0 affected421 at risk
Acrophobia	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected430 at risk EG0011 events1 affected421 at risk

ID	Term
C016752	smecta

Participants received matching placebo as 2 sachets, TID (2 sachets in the morning, 2 sachets at mid-day, and 2 sachets in the evening). Each sachet was taken in half a glass of water.

The mandatory treatment period was from Day 1 to Day 4 or Day 5 (with a minimum of 24 sachets taken within 4 or 5 days). Treatment could continue from Day 5 up to Day 8 or 9 (with a maximum of 48 sachets taken within 8 or 9 days).

Units	Counts
Participants	OG000413 OG001412

Units	Counts
Participants	OG000413 OG001412