lacebo
(N=403) Treatment Difference
[95% CI]
Combined Responder*
(Abdominal Pain and CSBM Responder) 12.1% 5.1% 7.0%
[3.2%, 10.9%] 12.7% 3.0% 9.7%
[6.1%, 13.4%]
Abdominal Pain Responder*
(≥ 30% Abdominal Pain Reduction) 34.3% 27.1% 7.2%
[0.9%, 13.6%] 38.9% 19.6% 19.3%
[13.2%, 25.4%]
CSBM Responder*
(≥ 3 CSBMs and Increase ≥1 CSBM from Baseline) 19.5% 6.3% 13.2%
[8.6%, 17.7%] 18.0% 5.0% 13.0%
[8.7%, 17.3%]
Table 4: Efficacy Responder Rates in the Two Placebo-controlled IBS-C Trials: at Least 6 Out of 12 Weeks * Primary Endpoint, ** Secondary Endpoints
Note: Analyses based on first 12 weeks of treatment for both Trials 1 and 2
CI =Confidence Interval
Trial 1 Trial 2
LINZESS
290 mcg
(N=405) Placebo
(N=395) Treatment Difference
[95% CI] LINZESS
290 mcg
(N=401) Placebo
(N=403) Treatment Difference
[95% CI]
Combined Responder*
(Abdominal Pain and CSBM Responder) 33.6% 21.0% 12.6%
[6.5%, 18.7%] 33.7% 13.9% 19.8%
[14.0%, 25.5%]
Abdominal Pain Responder**
(≥ 30% Abdominal Pain Reduction) 50.1% 37.5% 12.7%
[5.8%, 19.5%] 48.9% 34.5% 14.4%
[7.6%, 21.1%]
CSBM Responder**
(Increase ≥ 1 CSBM from Baseline) 48.6% 29.6% 19.0%
[12.4%, 25.7%] 47.6% 22.6% 25.1%
[18.7%, 31.4%]
In each trial, improvement from baseline in abdominal pain and CSBM frequency was seen over the first 12-weeks of the treatment periods. For change from baseline in the 11-point abdominal pain scale, LINZESS 290 mcg began to separate from placebo in the first week. Maximum effects were seen at weeks 6 - 9 and were maintained until the end of the study. The mean treatment difference from placebo at week 12 was a decrease in pain score of approximately 1.0 point in both trials (using an 11-point scale). Maximum effect on CSBM frequency occurred within the first week, and for change from baseline in CSBM frequency at week 12, the difference between placebo and LINZESS was approximately 1.5 CSBMs per week in both trials.
During the 4-week randomized withdrawal period in Trial 1, patients who received LINZESS during the 12-week treatment period were re-randomized to receive placebo or continue treatment on LINZESS 290 mcg. In LINZESS-treated patients re-randomized to placebo, CSBM frequency and abdominal-pain severity returned toward baseline within 1 week and did not result in worsening compared to baseline. Patients who continued on LINZESS maintained their response to therapy over the additional 4 weeks. Patients on placebo who were allocated to LINZESS had an increase in CSBM frequency and abdominal pain levels that were similar to the levels observed in patients taking LINZESS during the treatment period.
13.214.2 Chronic Idiopathic Constipation (CIC)
The efficacy of LINZESS for the management of symptoms of CIC was established in two double-blind, placebo-controlled, randomized, mu
