Irritable Bowel Syndrome (IBS) is the most commonly identified functional gastrointestinal
disorder, affecting 10-20% of the population in the Western world, seen predominantly in
females and with a negative impact on quality of life, characterized by recurrent and often
disabling abdominal pain associated with altered frequency or appearance or passage of the
stool.
IBS aetiology is unknown and its treatment remains largely empirical and directed to the
relief of symptoms. One possible target for IBS treatment has been identified in drugs that
modulate the action of Cholecystokinin (CCK), a peptide gut hormone implicated in the
regulation of motor and sensory functions at various levels of the gastrointestinal tract.
The biological actions of CCK in the gastrointestinal tract are mediated by CCK1-receptors.
Dexloxiglumide is an oral potent and selective antagonist of CCK1-receptors. The mechanism by
which dexloxiglumide might be beneficial in IBS is its ability to modulate visceral
hypersensitivity and gut dysmotility.
The DARWIN study has been designed to confirm the efficacy of dexloxiglumide according to a
so-called randomized/withdrawal design. In this design all participants start the study
treatment and only improved patients (the "responders") are randomized to active treatment or
placebo, expecting a more frequent and/or a more rapid relapse of their symptoms in patients
randomised to placebo than those on active.
Female and male patients, aged 18-70 yrs meeting IBS diagnostic criteria whose main complain
is constipation, with a disease of at least moderate severity, will receive dexloxiglumide or
placebo during a double-blind treatment phase of 24 weeks, following a first treatment of up
to 12 wks during which patients will have to qualify as "responders" to the study treatment.
The responder status of each patient over each 4-wk assessment period, will be based on a
weekly global patient-based assessment of relief and control of symptoms using a
telephone/internet-based diary.
Additional secondary efficacy parameters will include: effect of treatment on IBS cardinal
symptoms (e.g. abdominal discomfort/pain, bloating, straining, incomplete evacuation,
urgency, stool frequency and consistency), on rescue laxative consumption, and on quality of
life.
Standard safety parameters include vital signs, adverse event reporting, physical
examination, routine laboratory screen, 12-lead ECG and gallbladder ultrasound.
