EFFICACY
IBS-C patient
CONSTIPATION RELIEF DATA

In pivotal studies, LINZESS helped provide relief of both constipation and abdominal pain in patients with IBS-C1

LINZESS was studied in over 1600 patients in 2 phase 3 trials. Trials 1 and 2 measured patients who experienced improved CSBM frequency, patients who experienced reduced abdominal pain, and patients who experienced both (combined responders) for at least 6 of 12 weeks and 9 of 12 weeks.

CSBM, complete spontaneous bowel movement; IBS-C, irritable bowel syndrome with constipation.

IBS-C efficacy combined responders IBS-C efficacy combined responders IBS-C efficacy combined responders

Significantly more combined responders1

IBS-C efficacy combined responder charts
IBS-C efficacy combined responder charts
IBS-C efficacy combined responder charts
IBS-C bowel movement frequency IBS-C bowel movement frequency IBS-C bowel movement frequency

Improved CSBM frequency1

IBS-C efficacy csbm frequency charts
IBS-C efficacy csbm frequency charts
IBS-C pain reduction IBS-C pain reduction IBS-C pain reduction

Reduced abdominal pain1

IBS-C efficacy abdominal pain charts
IBS-C efficacy abdominal pain charts
IBS-C efficacy abdominal pain charts

Significantly more patients treated with LINZESS 290 mcg were combined responders than placebo-treated patients1,*

*In the IBS-C trials, significantly more patients treated with LINZESS were combined responders than placebo-treated patients. For the 6 out of 12 week combined responder endpoint, a patient had to have at least a 30% reduction from baseline in mean abdominal pain and an increase of at least 1 CSBM from baseline, all in the same week, for at least 6 out of 12 weeks. For the 9 out of 12 weeks combined responder endpoint, a patient had to have at least a 30% reduction from baseline in mean abdominal pain, at least 3 CSBMs and an increase of at least 1 CSBM from baseline, all in the same week, for at least 9 out of the first 12 weeks of treatment.1

Clinical trial design

Two phase 3 clinical trials (Trial 1 and Trial 2) compared LINZESS 290 mcg vs placebo1

  • In Trials 1 and 2, the abdominal pain responder, 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
  • Trial designs were identical for the first 12 weeks. Thereafter, Trial 1 included a 4-week, randomized withdrawal (RW) period, and Trial 2 continued for 14 additional weeks (total of 26 weeks)

Patients were on average 44 years of age (range 18-87 years), 90% female, 77% white, 19% black, and 12% Hispanic1

Adult men and women were required to meet Rome II criteria for irritable bowel syndrome† (IBS) and also report during the 2-week pretreatment period1:

  • Mean abdominal pain score of ≥3 on an 11-point (0 to 10) numeric rating scale
  • <3 CSBMs per week and ≤5 spontaneous bowel movements (SBMs) per week
  • Patients who were allowed to continue stable doses of bulk laxatives (eg, fiber) or stool softeners1

Patients were not allowed to take osmotic or stimulant laxatives, bismuth, prokinetic agents, or other drugs to treat IBS-C

†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.

In a phase 3b trial, LINZESS improved overall abdominal symptoms (bloating, pain, discomfort)1,2

Improvement vs placebo was observed at week 1 and continued through 12 weeks

A 12-week randomized, double-blind, placebo-controlled phase 3b clinical study in adult IBS-C patients (N=614) with a 4-week randomized withdrawal period (post-treatment). Primary endpoint: Change from baseline in the multicomponent abdominal score throughout the treatment period based on the mean abdominal score across treatment weeks obtained using the average daily assessments of abdominal bloating, abdominal pain, and abdominal discomfort. Each abdominal symptom was rated on a 0- to 10-point numeric rating scale where 0=no [symptom] and 10=worst possible [symptom]. Baseline abdominal scores: 6.4 for LINZESS and 6.5 for placebo. The adverse event profile was consistent with the pivotal trials.

IBS-C trial abdominal symptoms
IBS-C trial abdominal symptoms

||Abdominal scores at baseline: 6.4 for LINZESS and 6.5 for placebo. Least squares 12-week mean change from baseline: -1.9 for LINZESS and -1.2 for placebo (P<0.0001).

IBS-C abdominal pain improvement
IBS-C abdominal pain improvement
IBS-C abdominal pain improvement
IBS-C abdominal pain improvement

Because these individual component analyses were not adjusted for multiplicity, individual component results need cautious interpretation and could represent chance findings.

IBS-C is more than constipation. LINZESS can help improve overall abdominal symptoms1

Set expectations with patients on LINZESS1

In pivotal studies, patients started to feel improvement in CSBM frequency and abdominal pain at week 1 and continued to improve through weeks 6 to 9.
Improvement was maintained until the end of the study

  • Diarrhea was the most commonly reported adverse reaction
IBS-C trial abdominal symptoms

IBS-C Trials 1 and 2: time to maximum CSBM frequency and abdominal pain improvement with LINZESS treatment1

  • This illustrative “line of best fit” graph depicts the time to maximum CSBM frequency and maximum abdominal pain improvement in trials evaluating LINZESS in adults with IBS-C (Trials 1 and 2)
  • In each IBS-C trial, maximum effect on CSBM frequency was reached within the first week of treatment with LINZESS and was maintained until the end of the trial
  • In each IBS-C trial, for change from baseline in the 11-point abdominal pain scale, LINZESS began to separate from placebo in the first week
  • Maximum effect on abdominal pain was seen at weeks 6 to 9 of treatment with LINZESS and was maintained until the end of the study

In clinical trials, patients experienced improvement in abdominal pain and more frequent CSBMs over the 12-week treatment period

  • During the 4-week randomized withdrawal period of Trial 1, LINZESS-treated patients rerandomized to placebo experienced a return in CSBM frequency and abdominal pain severity toward baseline within 1 week and did not result in worsening compared to baseline1

Patients who continued on LINZESS maintained their response for the additional 4 weeks of the study1

  • Placebo-treated patients rerandomized to LINZESS experienced an increase of CSBM frequency and a decrease in abdominal pain within 1 week similar to the levels observed in patients taking LINZESS during the treatment period

Most patients showed improvement in CSBM frequency and abdominal pain at week 1 and continued to improve through weeks 6 to 9 in pivotal studies1