While estimates vary, as many as 2 in 10 adults in the United States suffer from symptoms of Irritable Bowel Syndrome with Constipation (IBS-C) or Chronic Idiopathic Constipation (CIC). LINZESS is a once-daily treatment that may allow patients with IBS-C or CIC to proactively manage their symptoms.1,2,5,12*
*While estimates may vary, as many as 13 million and 35 million adult Americans suffer from symptoms of IBS-C or CIC, respectively.
LINZESS was studied in 2 double-blind, placebo-controlled, randomized, multicenter trials for the management of symptoms in adult patients with IBS-C. In Trials 1 and 2, the abdominal pain responder, complete spontaneous bowel movement (CSBM†) responder, and combined responder endpoints were based on a patient being a weekly responder for either at least 9 out of the first 12 weeks of treatment, or at least 6 out of the first 12 weeks of treatment.1
†CSBM is defined as a spontaneous bowel movement (SBM) that is associated with a sense of complete evacuation. SBM is defined as a bowel movement without the use of a laxative.1
‡Patients reported for at least 12 weeks (which need not be consecutive), in the preceding 12 months, abdominal discomfort or pain that had ≥2 of these features: relieved with defecation, onset associated with a change in frequency of stool, and/or onset associated with a change in form (appearance) of stool.1,15
Baseline abdominal pain scores in IBS-C clinical trials ranged from 3 to 10 on a 0-10 scale 2,20,21
Baseline number of CSBMs per week ranged from 0 to 2.92,20,21
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a primary endpoint in individual trials. Trial1: Trt Diff 7.2%, 95% CI (0.9%, 13.6%). Trial 2: Trt Diff 19.3%,95% CI (13.2%, 25.4%).
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a prespecified secondary endpoint in individual trials. Trial 1: Trt Diff 12.7%, 95% CI (5.8%, 19.5%). Trial 2: Trt Diff 14.4%, 95% CI (7.6%, 21.1%).
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a primary endpoint in individual trials. Trial1: Trt Diff 7.2%, 95% CI (0.9%, 13.6%). Trial 2: Trt Diff 19.3%,95% CI (13.2%, 25.4%).
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a prespecified secondary endpoint in individual trials. Trial 1: Trt Diff 12.7%, 95% CI (5.8%, 19.5%). Trial 2: Trt Diff 14.4%, 95% CI (7.6%, 21.1%).
9 out of 12 weeks
More than twice as many LINZESS-treated patients were combined responders1
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a primary endpoint in individual trials. Trial 1: Trt Diff 7.0%, 95% CI (3.2%, 10.9%). Trial 2: Trt Diff 9.7%, 95% CI (6.1%, 13.4%).
6 out of 12 weeks
34% of LINZESS-treated patients were combined responders1
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. The data above represent a primary endpoint in individual trials. Trial 1: Trt Diff 12.6%, 95% CI (6.5%, 18.7%). Trial 2: Trt Diff 19.8%, 95% CI (14.0%, 25.5%)
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. Trial 1: Mean Trt Diff -0.9, 95% CI (-1.2, -0.6). Trial 2: Mean Trt Diff -1.1, 95% CI (-1.4, -0.8).
Number of patients with a value at baseline: Trial 1: LIN n=405, PBO n=395; Trial 2: LIN n=401, PBO n=403.
Number of patients with Week 12 value: Trial 1: LIN n=314, PBO n=338; Trial 2: LIN n=316, PBO n=323.
Percentage reduction calculation based on mean score at baseline compared with mean score at Week 12
Results from 2 Phase 3 clinical trials with identical designs comparing LINZESS 290 mcg vs placebo for 12 weeks. Trial 1: Mean Trt Diff 1.5, 95% CI (1.1, 1.9). Trial 2: Mean Trt Diff 1.6, 95% CI (1.2, 2.0).
Number of patients with a value at baseline: Trial 1: LIN n=405, PBO n=395; Trial 2: LIN n=401, PBO n=403.
Number of patients with Week 12 value: Trial 1: LIN n=321, PBO n=341; Trial 2: LIN n=326, PBO n=335.
In addition to improvements in abdominal pain and CSBM frequency over the first 12 weeks of the treatment period, the following improvements were observed in each trial when LINZESS was compared with placebo: SBM frequency (SBMs/week), stool consistency (as measured by the Bristol Stool Form Scale [BSFS]), and amount of straining during bowel movements (amount of time pushing or physical effort to pass stool).1,2,22
LINZESS was studied in 3 phase 3, double-blind, placebo-controlled, randomized, multicenter clinical trials for the management of symptoms in adult patients with CIC. Trials 3, 4, and 5 evaluated complete spontaneous bowel movement (CSBM*) responders based on 2 criteria. A CSBM responder was defined as a patient who had at least 3 CSBMs and an increase of at least 1 CSBM from baseline in a given week for at least 9 weeks out of the 12-week treatment period.1
In Trial 5, a separate analysis was performed where a CSBM Sustained Responder was defined as a patient who had at least 3 CSBMs and an increase of at least 1 CSBM from baseline in a given week for at least 9 weeks out of the 12-week treatment period and at least 3 of the last 4 weeks of the treatment period.
*CSBM is defined as a spontaneous bowel movement (SBM) that is associated with a sense of complete evacuation. SBM is defined as a bowel movement without the use of a laxative.1
†Patients reported one of the following symptoms for at least 12 weeks, which need not be consecutive, in the preceding 12 months: straining in more than 25% of defecations, lumpy or hard stools in more than 25% of defecations, sensation of incomplete evacuation in more than 25% of defecations.1
‡Patients reported less than 3 SBMs per week and reported 1 or more of the following symptoms during the 3 months before the diagnosis with the onset at least 6 months before the diagnosis: straining during at least 25% of BMs, (b) lumpy or hard stools during at least 25% of BMs, and (c) a sensation of incomplete evacuation during at least 25% of BMs.
Baseline number of CSBMs per week ranged from 0 to 2.92,20,21
Baseline frequency of SBMs per week ranged from 0 to 61,2,23
§Stool consistency was assessed using the 7-point Bristol Stool Form Scale. The scale illustrates various stool forms, ranging from 1-7 (Types 1 and 2 are consistent with constipation; Types 6 and 7 are consistent with diarrhea).1,22
Results from 3 Phase 3 clinical trials with identical designs comparing LINZESS 145 mcg vs placebo (Trials 3 and 4) or LINZESS 72 mcg (Trial 5) vs placebo for 12 weeks. The data above represent a primary endpoint in individual trials. Trial 3: Trt Diff 17%, 95% CI (11.0%, 22.8%). Trial 4: Trt Diff 10%, 95% CI (4.2%, 15.7%).Trial 5: Trt Diff 9%, 95% CI (4.8%,12.5%)
Results from 3 Phase 3 clinical trials with identical designs comparing LINZESS 145 mcg vs placebo (Trials 3 and 4) or LINZESS 72 mcg (Trial 5) vs placebo for 12 weeks. Trial 3: Mean Trt Diff 1.9, 95% CI (1.2, 2.6). Trial 4: Mean Trt Diff 1.7, 95% CI (1.0, 2.4). Trial 5: Trt Diff 0.7, 95% CI (0.2,1.2).
Number of patients with a value at baseline: Trial 3: LIN n=217, PBO n=209; Trial 4: LIN n=213, PBO n=215; Trial 5: LIN n=411, PBO n=401.
Number of patients with Week 12 value: Trial 3: LIN n=191, PBO n=181; Trial 4: LIN n=172, PBO n=191; Trial 5: LIN n=368, PBO n=356.
Results from 3 Phase 3 clinical trials with identical designs comparing LINZESS 145 mcg vs placebo (Trials 3 and 4) or LINZESS 72 mcg (Trial 5) vs placebo for 12 weeks. Trial 3: Mean Trt Diff 1.5, 95% CI (0.9, 2.1). Trial 4: Mean Trt Diff 1.3, 95% CI (0.8, 1.9).Trial 5: Trt Diff 0.7, 95% CI (0.3,1.2).
Number of patients with a value at baseline: Trial 3: LIN n=217, PBO n=209; Trial 4: LIN n=213, PBO n=215; Trial 5: LIN n=411, PBO n=401.
Number of patients with Week 12 value: Trial 3: LIN n=191, PBO n=181; Trial 4: LIN n=172, PBO n=191; Trial 5: LIN n=368, PBO n=356.
Stool consistency was assessed using the 7-point Bristol Stool Form Scale.
Results from 3 Phase 3 clinical trials with identical designs comparing LINZESS 145 mcg vs placebo (Trials 3 and 4) or LINZESS 72 mcg (Trial 5) vs placebo for 12 weeks. Trial 3: Mean Trt Diff 1.3, 95% CI (1.0, 1.6). Trial 4: Mean Trt Diff 1.1, 95% CI (0.7, 1.4). Trial 5: Trt Diff 0.6, 95% CI (0.4,0.8).
Number of patients with a value at baseline: Trial 3: LIN n=188, PBO n=180; Trial 4: LIN n=185, PBO n=190; Trial 5: LIN n=317, PBO n=297.
Patient numbers at baseline include all patients who had a baseline SBM value greater than zero.
Number of patients with Week 12 value: Trial 3: LIN n=155, PBO n=134; Trial 4: LIN n=127, PBO n=137; Trial 5: LIN n=276, PBO n=276.
Results from 3 Phase 3 clinical trials with identical designs comparing LINZESS 145 mcg vs placebo (Trials 3 and 4) or LINZESS 72 mcg (Trial 5) vs placebo for 12 weeks. Amount of straining was assessed on a 5-point ordinal scale ranging from 1 to 5, with higher scores indicating more straining.
Percent reduction in the amount of straining was calculated based on the mean baseline score and mean change from baseline during the 12-week treatment period.
Number of patients with a value at baseline: Trial 3: LIN n=175, PBO n=159; Trial 4: LIN n=175, PBO n=156; Trial 5: LIN n=317, PBO n=297.
Number of patients with Week 12 value: Trial 3: LIN n=155, PBO n=134; Trial 4: LIN n=127, PBO n=137; Trial 5: LIN n=276, PBO n=276.