The purpose of this study is to determine whether asimadoline is safe and effective at treating D-IBS.

The primary objective of the study is to compare the efficacy of the two treatments with respect to improvement in IBS-related abdominal pain severity and reduction in stool frequency. During the 12-week treatment period, daily IBS-related abdominal pain severity score and daily frequency of bowel movements will be averaged over each week to determine average values for each endpoint. For each subject, weekly response to treatment will be based on the following parameters:

• Decrease from baseline of at least 30% in the average IBS-related daily abdominal pain severity score
• Decrease from baseline of at least 25% in the average number of daily bowel movements A subject must meet both criteria to be considered a weekly responder. The primary efficacy endpoint is based on an "overall study responder," defined as a subject having 6 or more weeks of weekly response to treatment out of the 12 weeks in the treatment period. Overall study responder will be stratified by timing of bowel preparation and endoscopy.

Inclusion Criteria:

1. Signs and dates a written informed consent form.

2. Male and female subjects aged 18-79 who are fluent in English

3. All subjects must use protocol specified contraceptive measures

4. The subject is or has been diagnosed with IBS with symptom onset at least 6 months prior to diagnosis. IBS is defined as the subject having recurrent abdominal pain or discomfort at least 3 days per month in the past 3 months associated with at least two of the following symptoms:

   Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool

5. The subject has been diagnosed with diarrhea-predominant IBS

6. Within 2 years of the randomization visit, the subject has normal results from a flexible sigmoidoscopy, a colonoscopy, or a barium enema plus flexible sigmoidoscopy, according to the subject's age by a specified algorithm.

Exclusion Criteria:

1. The subject exhibits evidence of a biochemical or structural abnormality of the digestive tract.
2. Subject has a concurrent illness or disability (excluding IBS) that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, GI, hematological, or neurological condition).
3. The subject has a family history of prolonged QT syndrome.
4. The subject has been diagnosed with a major psychiatric disorder.
5. The subject has a history of alcohol or substance abuse within the past 2 years.
6. The subject has a history or current evidence of laxative abuse
7. The subject has a positive stool sample for ova or parasite.
8. The subject has used an investigational drug or participated in an investigational study within 30 days of screening.
9. The subject refuses to discontinue one (or more) prohibited medications at least 7 days prior to the screening visit.
10. The subject refuses to maintain a stable dose of one (or more) allowable concurrent medications for at least 30 days prior to the screening visit.
11. The subject is a pregnant woman or a woman who is breast feeding.
12. The subject is unable or unwilling to follow directions or use the electronic diary system.