Comparison of Lubiprostone and Placebo for the Relief of Constipation From Constipating Medications

Lubiprostone is a novel chloride channel activator that increases intestinal fluid secretion
and motility. It is FDA approved and indicated for treatment of chronic idiopathic
constipation and recently, constipation-predominant irritable bowel syndrome.

The Physicians Desk Reference lists over 90 Brand medications with reported incidence
associated with constipation over 3%. Little data are available about treatment responses. A
recent publication by our group reported treatment success for medication constipation using
polyethylene glycol. Since ongoing studies are addressing the role of lubiprostone in opioid
constipation, this work will be enrolling medication constipation study subjects not using
opioids.

In this study, patients who meet diagnostic criteria for constipation will be randomized to
receive 28 days of treatment with lubiprostone 24mcg twice a day. Data will be collected to
evaluate therapeutic outcome.

Inclusion Criteria:

- Adult male or female outpatient age 19 or older.

- Patients meet International Congress of Gastroenterology (ROME III) clinical criteria
for constipation*:

1. Must include two or more of the following:

1. Straining in > 1/4 defecations;

2. Lumpy or hard stools > 1/4 defecations;

3. Sensation of incomplete evacuation in 1/4 defecations;

4. Sensation of anorectal obstruction/blockage in > 1/4 defecations;

5. <3 defecations/week.

2. Loose stools are rarely present without the use of laxatives.

3. There are insufficient criteria for irritable bowel syndrome. *Criteria fulfilled
for the last 3 months with symptom onset at least 6 months prior to diagnosis.

- Use of one or more of listed medications known to cause constipation.

- If female and of childbearing potential, patient must be surgically sterilized or
using oral contraceptives, depot contraceptives, intrauterine device, or testifies
that she is monogamous with a vasectomized partner, or practices abstinence and will
continue to do so during the duration of study. Mandatory compliance is required.
Serum pregnancy tests will be performed at screening and during needed follow-up.
Negative results will be received before inclusion and administration of first study
dose. If pregnancy occurs during the trial, the investigator is notified immediately
resulting in prompt discontinuation.

- Study subjects must not have received lubiprostone for more than 72 hours.

- Written informed consent.

Exclusion Criteria:

- Known or suspected obstruction, gastric retention, ileus, perforation, fecal impaction
or inflammatory bowel disease.

- Severe diarrhea.

- Prior small bowel or colonic resection or colostomy.

- Weight < 80 lbs.

- If the patient has constipation that according to the investigator's clinical judgment
is not the result of constipating medications but is suffering from a secondary cause
including but limited to factors that are dietary, neurologic, congenital, diabetic or
hypothyroid.

- Positive stool hemoccult (Can be included if colonoscopic evaluation is subsequently
negative).

- Significant cardiac, renal or hepatic insufficiency.

- Pregnant or expecting to become pregnant within 120 days of study enrollment.

- Lactating or breast feeding.

- Subjects using opioid medications.

- Subjects who in the opinion of the investigator would be unable to comply adequately
with the study plan.

- Use of investigational drugs in the last 30 days.

- Patients with known allergy to lubiprostone.