Assessment of elemental impurities level after chronic administration of Diosmectite (SMECTA®) in subjects with chronic diarrhoea.

Diosmectite is a drug that is used in children and adults in the treatment of
acute diarrhea. Furthermore, it is used in adults in the treatment of chronic
diarrhea or pain associated with functional bowel disorders. Diosmectite is a
natural clay that helps repair intestinal damage with its
natural coating properties. Diosmectite is extracted from special geological
deposits and then cleaned and purified according to standards for medicinal
use. Diosmectite is not a new drug; it is already available in the market in
more than 70 countries for more than 40 years. In the current
study, diosmectite will be provided as Smecta® oral solution with
orange-vanilla flavor. Traces of metals can be present in Smecta® as they are
natural components of clay. Recent International guidelines are limiting the
amount of metals that can be traced in drug products. It is,
however, unknown how much of these metal traces could be absorbed by the body
when Smecta® is taken for a long period of time by patients with chronic
diarrhea.

The primary purpose of the study is to investigate how quickly and to what
extent traces of metals that are naturally present in Smecta® could be absorbed
and eliminated from the body (this is called pharmacokinetics). For exploratory
purposes, the potential effects of Smecta® on the
microbe population living in the intestine (formally called gut flora), will be
investigated in feces before, during and after the chronic administration of
Smecta®.

The actual study will consist of one treatment period of 35 days (5 weeks). Day
1 (Visit 2) is the first day of administration of the study compound. First,
the volunteers will stay for one period of 3 days (2 nights; from Day -1 to Day
2) in the clinical research center in Groningen (location Martini
Hospital). The day before first administration of the study compound they are
expected in the clinical research center at 07:00 in the morning*.
During the treatment period they will return to the clinical research center
for 4 short visits (at 11:00 in the morning on Days 8, 15, 22 and 29 [Visits 3
to 6]) during which theu will take their dose at noon, and one stay in the
clinical research center from Day 35 to Day 36 (location Martini
Hospital). For this stay in the clinical research center they are expected at
07:00 in the morning of Day 35* and they will leave the clinical research
center after completion of the assessments in the morning of Day 36.

Thereafter the volunteers will return for 3 post-study screenings (Visit 7 to
9) in the clinical research center in Groningen (location Martini Hospital),
once a month for 3 months. These include one stay in the clinical research
center from Day 65 to Day 66, another stay from Day 95 to Day 96, and a final
short visit on Day 125 (± 7 days). For the stays on Day 65 and Day 95 they are
expected in the clinical research center at 07:00 in the morning*. They will be
discharged from the study after completion of the last visit (Day 125, Visit
10) for follow-up assessments. The appointment for Day 125 will be made when
they are in the clinical research center. * For the admissions at 07:00 in the
morning of Day -1, Day 35, Day 65 and Day 95, there may be an option to enter
the clinical research center at 20:30 in the evening before these days (Day -2,
Day 34, Day 64 and Day 94, respectively). These options and any consequences
for the remuneration will be discussed with the volunteers before admission.
The participation to the entire study, from the pre-study screening until the
post-study screening, will be approximately 5.5 months.

Diosmectite (Smecta® 3g/sachet, powder for oral suspension. Three sachets per
day (TID). (morning, noon, and evening).
For the purpose of this study, Smecta® should be taken fasting and at least one
hour before meal, except for breakfast at least * hour before.

Pain, minor bleedings, bruises, possibly an infection.