(appearance) of stool.
Symptoms that Cumulatively Support the Diagnosis of Irritable Bowel Syndrome:
– Abnormal stool frequency (for research purposes “abnormal” may be defined as greater than 3 bowel movements per day and less than 3 bowel movements per week); Abnormal stool form (lumpy/hard or loose/watery stool); Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); Passage of mucus; Bloating or feeling of abdominal distension.
Trial 3 - Design
Trial 3 eva luated repeat treatment in adults with IBS-D meeting Rome III criteria** for up to 46 weeks. A total of 2579 were enrolled to receive open-label XIFAXAN for 14 days. Of 2438 eva luable patients, 1074 (44%) responded to initial treatment and were eva luated over 22 weeks for continued response or recurrence of IBS-symptoms. A total of 636 patients had symptom recurrence and were randomized into the double-blind phase of the study. These patients were scheduled to receive XIFAXAN 550 mg three times a day (n=328) or placebo (n=308) for two additional 14-day repeat treatment courses separated by 10 weeks. See Figure 3.
Figure 3
Figure 3: Trial 3 Study Design
The IBS-D population from the three studies had mean age of 47 (range: 18 to 88) years of which approximately 11% of patients were ≥65 years old, 72% were female and 88% were White.
**Rome III Criteria: Recurrent abdominal pain or discomfort (uncomfortable sensation not described as pain) at least 3 days/month in last 3 months associated with two or more of the following: 1. Improvement with defecation; 2. Onset associated with a change in frequency of stool; 3. Onset associated with a change in form (appearance) of stool.
Trials 1 and 2 - Results
Trials 1 and 2 included 1258 IBS-D patients (309 XIFAXAN, 314 placebo); (315 XIFAXAN, 320 placebo). The primary endpoint for both trials was the proportion of patients who achieved adequate relief of IBS signs and symptoms for at least 2 of 4 weeks during the month following 14 days of treatment. Adequate relief was defined as a response of “yes” to the following weekly Subject Global Assessment (SGA) question: “In regards to your IBS symptoms, compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? [Yes/No].”
Adequate relief of IBS symptoms was experienced by more patients receiving XIFAXAN than those receiving placebo during the month following 2 weeks of treatment (SGA-IBS Weekly Results: 41% vs. 31%, p=0.0125; 41% vs. 32%, p=0.0263 (See Table 6).
Table 6. Adequate Relief of IBS Symptoms During the Month Following Two Weeks of Treatment
Confidence Interval
The p-value for the primary endpoint for Trial 1 and for Trial 2 was <0.05.
The trials examined a composite endpoint which defined responders by IBS-related abdominal pain and stool consistency measures. Patients were monthly responders if they met both of the following criteria:
•experienced a ≥30% decrease from baseline in abdominal pain for ≥2 weeks during the month following 2 weeks of treatment
•had a weekly mean stool consistency score <4 (loose stool) for ≥2 weeks during the month following 2 weeks of treatment
More patients receiving XIFAXAN were monthly responders for abdominal pain and stool consistency in Trials 1 and 2 (see Table 7).
Table 7. Efficacy Responder Rates in Trial 1 and 2 During the Month Following Two Weeks of Treatment
Confidence Interval
The p-value f |
