or the composite endpoint for Trial 1 and 2 was <0.05 and <0.01, respectively.
Trial 3 - Results
In TARGET 3, 2579 patients were scheduled to receive an initial 14-day course of open-label XIFAXAN followed by 4 weeks of treatment-free follow-up. At the end of the follow-up period, patients were assessed for response to treatment. Patients were considered a responder if they achieved both of the following:
•≥30% improvement from baseline in the weekly average abdominal pain score based on the daily question: “In regards to your specific IBS symptoms of abdominal pain, on a scale of 0-10, what was your worst IBS-related abdominal pain over the last 24 hours? ‘Zero’ means you have no pain at all; ‘Ten’ means the worst possible pain you can imagine”.
•at least a 50% reduction in the number of days in a week with a daily stool consistency of Bristol Stool Scale type 6 or 7 compared with baseline where 6=fluffy pieces with ragged edges, a mushy stool; 7=watery stool, no solid pieces; entirely liquid.
Responders were then followed for recurrence of their IBS-related symptoms of abdominal pain or mushy/watery stool consistency for up to 20 treatment-free weeks.
When patients experienced recurrence of their symptoms of abdominal pain or mushy/watery stool consistency for 3 weeks of a rolling 4-week period, they were randomized into the double-blind, placebo-controlled repeat treatment phase. Of 1074 patients who responded to open-label XIFAXAN, 382 experienced a period of symptom inactivity or decrease that did not require repeat treatment by the time they discontinued, including patients who completed the 22 weeks after initial treatment with XIFAXAN. See Figure 3.
Overall, 1257 of 2579 patients (49%) were nonresponders in the open-label phase and per the study protocol were withdrawn from the study. Other reasons for discontinuation include: patient request (5%), patient lost to follow-up (4%), adverse reaction (3%), and other (0.8%).
There were 1074 (44%) of 2438 eva luable patients who responded to initial treatment with improvement in abdominal pain and stool consistency. The response rate for each IBS symptom during the open-label phase of Trial 3 is similar to the rates seen in Trials 1 and 2 (see Table 7). A total of 636 patients subsequently had sign and symptom recurrence and were randomized to the repeat treatment phase. The median time to recurrence for patients who experienced initial response during the open-label phase with XIFAXAN was 10 weeks (range 6 to 24 weeks).
The XIFAXAN and placebo treatment groups had similar baseline IBS symptom scores at the time of recurrence and randomization to the double-blind phase, but symptom scores were less severe than at study entry into the open-label phase.
Patients were deemed to have recurrent signs and symptoms by the following criteria: a return of abdominal pain or lack of stool consistency for at least 3 weeks during a 4-week follow-up period. The primary endpoint in the double-blind, placebo-controlled portion of the trial was the proportion of patients who were responders to repeat treatment in both IBS-related abdominal pain and stool consistency as defined above during the 4 weeks following the first repeat treatment with XIFAXAN. The primary analysis was performed using the worst case analysis method where patients with <4 days of diary entries in a given week are considered as non-responders for that week.
More patients receiving XIFAXAN were monthly res |
