DARWIN Study: A Randomization/Withdrawal Efficacy Study of Dexloxiglumide in Constipation-Predominant Irritable Bowel Syndrome (C-IBS)

Study Overview
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Brief Summary
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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.

Official Title
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A 24-wk, Prospective, d/b, Placebo Controlled, Parallel Group, Multicenter, Randomized/Withdrawal Efficacy and Safety Study of Dexloxiglumide for the Relief of Symptoms in Patients With Constipation-Predominant Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: dexloxiglumide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rome II criteria for IBS and manifesting supportive symptoms for the sub-classification of C-IBS, with a disease of at least moderate severity. Exclusion Criteria: standard exclusions apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: dexloxiglumide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to relapse, i.e. loss of responder status, which is based on a global patient-based weekly assessment of relief and control of symptoms |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| abdominal discomfort/pain |  |  | 
| bloating |  |  | 
| straining |  |  | 
| incomplete evacuation |  |  | 
| urgency |  |  | 
| stool frequency and consistency |  |  | 
| quality of life |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome, Cholecystokinin, Dexloxiglumide, Randomized/withdrawal