MRI Assessment of Mode of Action of Bisacodyl, Single Dose
MRI Assessment of Mode of Action of Bisacodyl, Single Dose
Constipation remains an important unmet medical need. Patients are currently often
 dissatisfied with treatment, because of lack of predictability of the laxative, side effects
 (mainly abdominal pain) and perceived decrease of efficacy with time. A recent systematic
 review of a range of laxatives reported that bisacodyl increases the number of complete
 spontaneous bowel movements statistically significant compared to placebo. Recently
 non-invasive Magnetic Resonance Imaging (MRI) techniques have been developed to assess small
 intestinal fluid distribution, transit and motility as well as colonic fluid, volumes and
 motility in healthy volunteers and constipated subjects. Other laxatives such as movecol and
 ispaghula have been investigated using this methodology. This study will use these novel
 techniques to further characterize bisacodyl's mode of action.

 This study is intended to assess the effect of a single-dose of bisacodyl on the gut motor
 function and its effect on water distribution within the small and large intestine in
 subjects with occasional constipation by MRI. It may allow better understanding of the
 relative importance of both the secretory and the prokinetic effect of bisacodyl.

 Since bisacodyl is often used by self-medicating people with constipation it is proposed to
 study subjects suffering from occasional constipation. As such subjects often take the drug
 intermittently it would be of interest to study both the acute response after single dose and
 the response after several days of treatment to see if this alters the response.

 The current study will be performed as a cross-over with 2-period and 2-treatment
 (bisacodyl/placebo), for assessing the effects over of a single-dose of 5mg bisacodyl.

 Evaluations will be performed after one single dose of bisacodyl or placebo in two different
 time periods, separated by a 2 week washout period between end of period 1 and start of
 period 2.

 The study will recruit individuals ≥18yrs from the general public who consider themselves as
 suffering from occasional constipation and who self-medicate with an occasional over-the
 counter (OTC) laxative, not more than once a week. Up to 18 adult healthy subjects will be
 recruited to ensure 10 evaluable subjects. An evaluable subject is defined as participant
 having the primary endpoint assessed (ascending colon T1 300, 375, and 450 minutes correctly
 evaluated) for the two periods of the crossover.
Inclusion Criteria:

 I 01. Adult subjects that self-medicate with occasional laxative no more than 4 times in
 the month before eligibility confirmation

 I 02. Meet Rome IV criteria for Chronic Constipation.

 I 03. ≥18 years of age inclusive, at the time of signing the informed consent.

 I 04. Screening diary confirms they experience at least 2 days in the 7 day diary with
 either hard stools (Bristol Stool form Score 1 or 2) or no bowel movement

 I 05. BMI under or equal to 35 kg/m2

 I 06. Female subjects of child bearing potential must have a negative urine pregnancy test
 at screening. Subjects of child bearing potential or with partners of child bearing
 potential must agree to use methods of medically acceptable forms of contraception during
 the study and for 90 days after completion of study drug, (e.g. implants, injectable,
 combined oral contraceptives, barrier methods, true abstinence (when this is in line with
 the preferred and usual lifestyle of the patient) or vasectomised partners).

 I 07. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1)
 which includes compliance with the requirements and restrictions listed in the informed
 consent form (ICF) and in this protocol.

 Exclusion Criteria:

 E 01. Known hypersensitivity or other contraindications to bisacodyl use: such as ileus,
 intestinal obstruction, acute abdominal conditions including appendicitis, acute
 inflammatory bowel diseases, and severe abdominal pain associated with nausea and vomiting;
 and severe dehydration or rare hereditary conditions that may be incompatible with an
 excipient of the product (galactose intolerance, e.g. galactosaemia, fructose intolerance.

 E 02. Pregnancy and/or breast breast-feeding or positive urine pregnancy test History of
 known gastrointestinal organic disease (i.e. celiac disease, inflammatory bowel diseases).

 E 03. A positive diagnosis of irritable bowel syndrome based on the Rome IV criteria
 questionnaire which requires the patient to experience abdominal pain at least weekly

 E 04. Reported history of previous major abdominal surgery (excluding appendectomy and
 cholecystectomy)

 E 05. Any medical condition making participation potentially compromising the participation
 in the study (e.g. diabetes mellitus, respiratory disease limiting ability to lie in the
 scanner, known allergy to one of the food products) as per investigator's judgment

 E 06. Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of
 metallic foreign body in eye(s) and penetrating eye injury

 E 07. Any condition incompatible with the patient's participation to the study as per
 investigator's judgment.

 E 08. Not willing or able agree to dietary restrictions required in 24 hours before each
 MRI study day

 E 09. Anticipate need for antibiotics intake during the study.

 E 10. Unwilling to stop probiotics for the duration of the study period

 E 11. Unable/ not willing to stop drugs known to alter GI motility including, regular
 loperamide, antispasmodics, (e.g. buscopan, mebeverine, peppermint oil, alverine citrate),
 eluxadoline opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium
 channel antagonists for the duration of the study (Selective serotonin reuptake inhibitors
 and low dose tricyclic antidepressants (< 30mg amitriptyline or 50mg nortriptyline) will be
 recorded but provided dose is stable, will not be an exclusion criteria).

 E 12. Having taken part in a research study within 3 months