Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids

This study will evaluate whether Colesevelam, a bile acid sequestrant, is able to reduce
fecal bile acids and improve bowel function in patients with IBS-diarrhea and Mayo's HPLC
method can demonstrate a response to the Colesevelam.

The study design will be a single center, unblinded, single dose trial to study the ability
to identify the effect of taking 1875 mg (3 tablets [625 mg/tablet]) of Colesevelam orally
twice daily for ten days on fasting serum 7alphaC4 and total 48 hour fecal bile acid
excretion. Stool and fasting serum samples will be collected predose and during final 48
hours' dosing for assessment. Participants will also fill out an 8-day stool diary assessing
frequency, consistency, ease of passage of bowel movements before and during treatment with
Colesevelam.

Patients with IBS-diarrhea with prior evidence of increased fecal 48 hour total bile acid
and increased fasting serum 7alphaC4 who meet the following:

INCLUSION CRITERIA

- Bowel disease questionnaire (BDQ) - IBS symptoms: Positive by Rome lll criteria

- No restrictions on Hospital Anxiety/Depression Score (HADS).

- Gender: Men or women. Women of childbearing potential will have a negative pregnancy
test before initiation of medication.

EXCLUSION CRITERIA

- Use of drugs or agents within the past 1 week or planned use in the subsequent 2
weeks during the study period (Birth control pill, estrogen replacement therapy, and
thyroxine replacement are permissible exceptions):

- Agents that alter GI transit including opioids, narcotics, anticholinergics,
tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRI)
antidepressants.

- Analgesic drugs including opiates, nonsteroidal anti-inflammatory drugs (NSAID),
cyclooxygenase-2 (COX 2) inhibitors

- Intake of medication that could interfere with the interpretation of the study.

- Female subjects who are pregnant or breast-feeding. Females must be either surgically
sterilized, postmenopausal (>12 months since last menses), or, if of childbearing
potential, using reliable methods of contraception as determined by the physician.

- Abdominal surgery (except Appendectomy)

- Patients with known chronic liver disease or history of elevated aspartate
aminotransferase (AST)/ alanine transaminase (ALT) 2.0 X upper limit of normal.

- Bile acid (BA) synthesis and possible false positive or negative fecal bile acid
or serum 7alpha-hydroxy-4-cholesten-3-one (7alphaC4) result. If there is no AST
or ALT values in the medical record, the study physicians will determine if the
tests need to be run.