Acute Diarrhoea
Conditions
Brief summary
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.
Interventions
DRUGSmecta
DRUGSmecta placebo
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery | From randomisation (Day 1) up to Day 9 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Diarrhoea Onset to First Formed Stool | From randomisation (Day 1) up to Day 9 | 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). |
| Time From the First Study Treatment Intake to the Last Watery Stool | From randomisation (Day 1) up to Day 9 | 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). |
| Number of Stools, Per 12-Hour Period | From randomisation (Day 1) up to Day 9 | Number of stools, per 12-hour period, was recorded in the DEB. |
| Time From Diarrhoea Onset to Recovery | From randomisation (Day 1) up to Day 9 | 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). |
| Percentage of Participants With Associated Symptoms, Per 12-Hour Period | From randomisation (Day 1) up to Day 9 | 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. |
| Abdominal Pain Intensity Scores, Per 12-Hour Period | From randomisation (Day 1) up to Day 9 | 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. |
| Number of Watery Stools, Per 12-Hour Period | From randomisation (Day 1) up to Day 9 | Number of watery stools, per 12-hour period, was recorded in the DEB. |
Countries
Algeria, Czechia, Egypt, Lebanon, Poland, Tunisia
Participant flow
Recruitment details
The study enrolled adult participants with a recent episode of acute diarrhoea presumed of infectious origin, defined as the passage of 3 or more unformed (loose or watery) stools per day without alarm symptoms within the first 48 hours. Participants were randomised at 62 study centres in Algeria, Czech Republic, Egypt, Lebanon, Poland and Tunisia.
Pre-assignment details
858 participants were randomised, of which 853 were included in the analysis and 5 were excluded due to invalid consent. Only participants included in the analysis are presented in the participant flow. Participants received a diary evaluation booklet (DEB) to record each stool plus consistency on a daily basis from inclusion until end of study.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 430 |
| 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). | 423 |
| Total Title | 853 |
| Total | 1,706 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Consent withdrawn | 4 | 4 |
| Overall Study | Lost to Follow-up | 13 | 5 |
| Overall Study | Other | 2 | 8 |
| Overall Study | Protocol Violation | 5 | 3 |
Baseline characteristics
| Characteristic | Diosmectite | Placebo | Total Title |
|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 14.5 | 38.6 years STANDARD_DEVIATION 14.2 | 39.1 years STANDARD_DEVIATION 14.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 232 Participants | 241 Participants | 473 Participants |
| Sex: Female, Male Male | 198 Participants | 182 Participants | 380 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 430 | 0 / 421 |
| other Total, other adverse events | 29 / 430 | 32 / 421 |
| serious Total, serious adverse events | 1 / 430 | 1 / 421 |
Outcome results
Primary
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).
Time frame: From randomisation (Day 1) up to Day 9
Population: The ITT population included all randomised participants (except for those excluded from the analysis), analysed according to the arm to which they were randomised.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diosmectite | Time to Recovery | 66.0 Hours |
| Placebo | Time to Recovery | 68.6 Hours |
Comparison: The primary analysis tested the equality of time to recovery between the 2 treatment groups, applying the 2-sided Gehan-Wilcoxon test (α=5%).p-value: =0.2524Wilcoxon-Gehan test
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.
Time frame: From randomisation (Day 1) up to Day 9
Population: 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 at each specified time point were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 168 - 180 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 12 - 24 hours | 1.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 24 - 36 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 36 - 48 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 48 - 60 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 60 - 72 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 72 - 84 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 84 - 96 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 96 - 108 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 108 - 120 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 120 - 132 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 132 - 144 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 144 - 156 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 156 - 168 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 180 - 192 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 192 - 204 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 204 - 216 hours | 0.0 Scores on a scale |
| Diosmectite | Abdominal Pain Intensity Scores, Per 12-Hour Period | 0 - 12 hours | 1.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 156 - 168 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 0 - 12 hours | 1.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 108 - 120 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 12 - 24 hours | 1.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 168 - 180 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 24 - 36 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 120 - 132 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 36 - 48 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 192 - 204 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 48 - 60 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 132 - 144 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 60 - 72 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 180 - 192 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 72 - 84 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 144 - 156 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 84 - 96 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 204 - 216 hours | 0.0 Scores on a scale |
| Placebo | Abdominal Pain Intensity Scores, Per 12-Hour Period | 96 - 108 hours | 0.0 Scores on a scale |
Secondary
Number of Stools, Per 12-Hour Period
Number of stools, per 12-hour period, was recorded in the DEB.
Time frame: From randomisation (Day 1) up to Day 9
Population: 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 at each specified time point were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Diosmectite | Number of Stools, Per 12-Hour Period | 108 - 120 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 60 - 72 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 120 - 132 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 36 - 48 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 132 - 144 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 72 - 84 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 144 - 156 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 24 - 36 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 156 - 168 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 84 - 96 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 168 - 180 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 48 - 60 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 180 - 192 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 96 - 108 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 192 - 204 hours | 1.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 12 - 24 hours | 2.0 Stools |
| Diosmectite | Number of Stools, Per 12-Hour Period | 0 - 12 hours | 3.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 192 - 204 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 204 - 216 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 0 - 12 hours | 3.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 12 - 24 hours | 2.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 24 - 36 hours | 2.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 36 - 48 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 48 - 60 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 60 - 72 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 72 - 84 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 84 - 96 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 96 - 108 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 108 - 120 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 120 - 132 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 132 - 144 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 144 - 156 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 156 - 168 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 168 - 180 hours | 1.0 Stools |
| Placebo | Number of Stools, Per 12-Hour Period | 180 - 192 hours | 1.0 Stools |
Comparison: Comparison between the 2 treatment groups for number of stools for the overall time period, based on an analysis of covariance (ANCOVA) method for repeated measurements. The model included the number of stools 24 hours before randomisation (baseline) as covariate, treatment, time point (12-hour period), the treatment by time point interaction as fixed effects and participant as random effect.p-value: 0.429495% CI: [-0.15, 0.07]ANCOVA
Secondary
Number of Watery Stools, Per 12-Hour Period
Number of watery stools, per 12-hour period, was recorded in the DEB.
Time frame: From randomisation (Day 1) up to Day 9
Population: 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 at each specified time point were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 108 - 120 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 60 - 72 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 120 - 132 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 36 - 48 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 132 - 144 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 72 - 84 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 144 - 156 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 24 - 36 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 156 - 168 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 84 - 96 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 168 - 180 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 48 - 60 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 180 - 192 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 96 - 108 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 192 - 204 hours | 0.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 12 - 24 hours | 1.0 Stools |
| Diosmectite | Number of Watery Stools, Per 12-Hour Period | 0 - 12 hours | 3.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 192 - 204 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 204 - 216 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 0 - 12 hours | 3.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 12 - 24 hours | 1.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 24 - 36 hours | 1.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 36 - 48 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 48 - 60 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 60 - 72 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 72 - 84 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 84 - 96 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 96 - 108 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 108 - 120 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 120 - 132 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 132 - 144 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 144 - 156 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 156 - 168 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 168 - 180 hours | 0.0 Stools |
| Placebo | Number of Watery Stools, Per 12-Hour Period | 180 - 192 hours | 0.0 Stools |
Comparison: Comparison between the 2 treatment groups for number of watery stools for the overall time period, based on an ANCOVA method for repeated measurements. The model included the number of watery stools 24 hours before randomisation (baseline) as covariate, treatment, time point (12-hour period), the treatment by time point interaction as fixed effects and participant as random effect.p-value: 0.046595% CI: [-0.24, 0]ANCOVA
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.
Time frame: From randomisation (Day 1) up to Day 9
Population: 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 at each specified time point were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 0 - 12 hours | 76.3 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 12 - 24 hours | 67.1 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 24 - 36 hours | 56.2 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 36 - 48 hours | 44.8 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 48 - 60 hours | 34.9 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 60 - 72 hours | 28.7 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 72 - 84 hours | 24.3 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 84 - 96 hours | 21.6 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 96 - 108 hours | 20.6 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 108 - 120 hours | 18.6 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 120 - 132 hours | 18.4 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 132 - 144 hours | 12.6 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 144 - 156 hours | 10.5 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 156 - 168 hours | 8.5 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 168 - 180 hours | 8.6 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 180 - 192 hours | 8.2 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 192 - 204 hours | 9.7 Percentage of participants |
| Diosmectite | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 204 - 216 hours | 5.9 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 156 - 168 hours | 16.1 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 0 - 12 hours | 76.4 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 108 - 120 hours | 24.9 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 12 - 24 hours | 64.6 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 204 - 216 hours | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 24 - 36 hours | 54.2 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 120 - 132 hours | 27.9 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 36 - 48 hours | 45.6 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 168 - 180 hours | 11.8 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 48 - 60 hours | 35.4 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 132 - 144 hours | 21.4 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 60 - 72 hours | 28.8 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 192 - 204 hours | 10.5 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 72 - 84 hours | 22.0 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 144 - 156 hours | 19.2 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 84 - 96 hours | 20.6 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 180 - 192 hours | 9.8 Percentage of participants |
| Placebo | Percentage of Participants With Associated Symptoms, Per 12-Hour Period | 96 - 108 hours | 24.0 Percentage of participants |
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).
Time frame: From randomisation (Day 1) up to Day 9
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diosmectite | Time From Diarrhoea Onset to First Formed Stool | 84.3 Hours |
| Placebo | Time From Diarrhoea Onset to First Formed Stool | 84.6 Hours |
Comparison: Comparison between the 2 treatment groups for time from diarrhoea onset to first formed stool, analysed using the Gehan-Wilcoxon test.p-value: =0.7285Gehan-Wilcoxon test
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).
Time frame: From randomisation (Day 1) up to Day 9
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diosmectite | Time From Diarrhoea Onset to Recovery | 91.0 Hours |
| Placebo | Time From Diarrhoea Onset to Recovery | 92.2 Hours |
Comparison: Comparison between the 2 treatment groups for time from diarrhoea onset to recovery, analysed using the Gehan-Wilcoxon test.p-value: =0.3511Gehan-Wilcoxon test
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).
Time frame: From randomisation (Day 1) up to Day 9
Population: The ITT population included all randomised participants (except for those excluded from the analysis), analysed according to the arm to which they were randomised.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diosmectite | Time From the First Study Treatment Intake to the Last Watery Stool | 56.2 Hours |
| Placebo | Time From the First Study Treatment Intake to the Last Watery Stool | 60.0 Hours |
Comparison: Comparison between the 2 treatment groups for time from first study treatment intake to last watery stool, analysed using the Gehan-Wilcoxon test.p-value: =0.1807Gehan-Wilcoxon test