DARWIN Study: A Randomization/Withdrawal Efficacy Study of Dexloxiglumide in Constipation-Predominant Irritable Bowel Syndrome (C-IBS)
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    


Intervention name(s): dexloxiglumide
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Irritable Bowel Syndrome; Cholecystokinin; Dexloxiglumide; Randomized/withdrawal