Study Demonstrated AMITIZA(TM) (lubiprostone) Showed Efficacy Within 24 and 48 Hours of Treatment

Results of a secondary analysis of two pivotal studies were presented today at the 71st Annual Meeting of the American College of Gastroenterology (ACG), and showed that 60 percent of patients treated with AMITIZA(TM) (lubiprostone) experienced a spontaneous bowel movement (SBM) within 24 hours of treatment, and 80 percent experienced a SBM within 48 hours of treatment. Additionally, AMITIZA, the first selective chloride channel activator approved by the FDA for the treatment of chronic idiopathic constipation in adults, showed improvement in long-term symptom relief of this disorder with significant improvements in constipation severity, abdominal bloating and discomfort for up to 12 months.

"These results are encouraging for physicians who treat patients with constipation because there are few treatments approved for chronic constipation that can be used long term," said Satish Rao, M.D., professor of medicine and director, Neurogastroenterology and GI Motility at University of Iowa. "These data indicate that lubiprostone may provide rapid and long-term relief of symptoms."

Constipation, one of the most common digestive complaints, accounts for more than 2.5 million doctor visits in the U.S. each year according to the ACG. It is a condition that often requires rapid and predictable relief of symptoms with limited long-term treatment options. In clinical studies, relief was defined as three or more SBMs per week.

AMITIZA has a novel mechanism of action that works by activating chloride channels to increase fluid secretion in the intestine, thereby increasing the passage of stool and improving signs and symptoms associated with chronic idiopathic constipation. AMITIZA is the only prescription medication for chronic idiopathic constipation that has been approved by the FDA for use in adults, including those 65 years and over and that has demonstrated effectiveness for use beyond 12 weeks.

Study Design: Spontaneous Bowel Movements within 24 Hours and 48 Hours

To determine the onset of action of AMITIZA within 24 and 48 hours, individual and pooled results from two well-controlled Phase III trials were examined: 239 participants received AMITIZA 24 mcg twice daily and 240 participants received placebo. Data on time to first SBM and percentage of patients experiencing a SBM within 24 and 48 hours following initial study-drug administration were compared by study and pooled between treatment groups (placebo vs. AMITIZA). For each study, the time to first SBM was significantly shorter for patients taking AMITIZA compared with those taking placebo (P is less than or equal to 0.006).

--  In the individual studies, 57 to 63 percent of patients treated with
    AMITIZA and 32 to 37 percent of placebo patients had a SBM within 24 hours
    (P is less than or equal to 0.0024).
--  At the 48-hour timepoint in the individual studies, a SBM occurred in
    79 to 80 percent of patients treated with AMITIZA vs. 61 to 66 percent of
    placebo patients (P is less than or equal to 0.0258).
--  In the pooled analysis, 60 percent of patients treated with AMITIZA
    had a SBM within 24 hours and 80 percent had a SBM within 48 hours,
    compared with 35 and 63 percent of placebo patients, respectively (P is
    less than 0.0001).

Study Design: Long-Term Use of AMITIZA

To evaluate the long-term safety of AMITIZA, a 48-week, open-label trial of patients who had not received AMITIZA before was conducted. In total, 324 participants with chronic idiopathic constipation received AMITIZA 24 mcg taken twice daily.

The findings revealed that AMITIZA was generally well tolerated throughout the study's duration. Sixty-seven percent of patients experienced at least one treatment-related adverse event (AE). The most common treatment-related AEs included nausea (30.2%) and diarrhea (19.4%). Improvements in assessments of constipation severity, abdominal bloating and abdominal discomfort were statistically significant at all visits compared to baseline (P is less than or equal to 0.001).

Further, patients were asked to assess constipation severity and abdominal symptoms of bloating and discomfort using a 5-point scale where 0=absent, 1=mild, 2=moderate, 3=severe and 4=very severe, at each study visit (approximately every 6 weeks). Specifically:

--  Constipation severity was improved by an average of 1.11 points at
    Week 1 (N=320), 1.17 points at Week 24 (N=183), 1.28 points at Week 48
    (N=152) and 0.99 points for the last on-drug measurement (N=320) from a
    mean baseline value of 2.69 (N=320).
--  Abdominal bloating was improved by an average of 0.70 points at Week 1
    (N=320), 0.80 points at Week 24 (N=183), 0.88 points at Week 48 (N=152) and
    0.68 points for the last on-drug measurement (N=320) from a mean baseline
    value of 1.88 (N=320).
--  Abdominal discomfort was improved by an average of 0.65 points at Week
    1 (N=320), 0.66 points at week 25 (N=183), 0.78 points at Week 48 (N=152)
    and 0.60 points for the last on-drug measurement (N=320) from a mean
    baseline value of 1.60 (N=320).