LINZESS provides effective symptom relief1

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).3-5* LINZESS is a once-daily treatment that may allow patients with IBS-C or CIC to proactively manage their symptoms.1

*While estimates may vary, as many as 13 million and 35 million adult Americans suffer from symptoms of IBS-C or CIC, respectively.

Use the buttons below to view the LINZESS clinical data for IBS-C and CIC.

LINZESS was evaluated in 2 IBS-C clinical trials of more than 1600 patients1


Clinical trial design

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


Trials evaluated abdominal pain responders, CSBM responders, and combined responders1

LINZESS was studied in:

  • Two Phase 3 clinical trials (Trial 1 and Trial 2) that compared LINZESS 290 mcg vs placebo1
    • 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 who were on average 44 years (range 18-87 years with 5% ≥65 years), 90% female, 77% white, 19% black, and 12% Hispanic1
  • Adult men and women who were required to meet Rome II criteria for 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 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.1,6

Patients with varying degrees of symptom severity were included in pivotal LINZESS trials1

Pretreatment symptoms and characteristics3,7,8

Baseline abdominal pain scores in IBS-C clinical trials ranged from 3 to 10 on a 0-10 scale 3,7,8

Baseline number of CSBMs per week ranged from 0 to 2.93,7,8

Patients had significant improvement in both abdominal pain and frequency of CSBMs1

More LINZESS-treated patients were abdominal pain and CSBM 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 7.2%, 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. Trial 1: Trt Diff 13.2%, 95% CI (8.6%, 17.7%). Trial 2: Trt Diff 13.0%, 95% CI (8.7%, 17.3%).

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 19.0%, 95% CI (12.4%, 25.7%). Trial 2: Trt Diff 25.1%, 95% CI (18.7%, 31.4%).

Significant responder rates in abdominal pain and in CSBMs vs placebo1

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%).

Relief from abdominal pain was maintained over the treatment period1

LINZESS reduced abdominal pain by ~2.5 points at Week 12, ~1 point more than placebo1,3

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.

Improvement in frequency of bowel movements was maintained over the treatment period1,3

LINZESS increased CSBM frequency by more than 2 CSBMs at Week 12, ~1.5 points more than placebo1,3

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.

  • Maximum effect on CSBM frequency occurred within the first week and was maintained through the end of the treatment period

Additional Improvements

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).1,3,9

LINZESS was evaluated in 3 CIC clinical trials of more than 2400 patients1

Clinical trial data

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

LINZESS was studied in1,10:

  • Two Phase 3 clinical trials (Trial 3 and Trial 4) that compared LINZESS 145 mcg vs placebo and one Phase 3 clinical trial (Trial 5) that compared LINZESS 72 mcg vs placebo
    • Trial designs were identical for the first 12 weeks. Thereafter, Trial 3 included a 4‑week randomized withdrawal (RW) period
  • Patients in Trials 3 and 4 were, on average, 48 years (range 18-85 years with 12% ≥65 years), 89% female, 76% white, 22% black, and 10% Hispanic. Patients in Trial 5 were, on average, 46 years (range 18-90 years), 77% female, 71% white, 24% black, and 43% Hispanic
  • For Trials 3 and 4, adult men and women who were required to meet modified Rome II criteria for functional constipation; patients reported <3 CSBMs and ≤6 SBMs per week during the 2-week baseline period. For Trial 5, all patients met modified Rome III criteria for functional constipation
  • Patients who were allowed to continue stable doses of bulk laxatives (eg, fiber) or stool softeners
    • Patients were not allowed to take osmotic or stimulant laxatives, bismuth, prokinetic agents, or other drugs to treat CIC
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.

Patients with varying degrees of symptom severity were included in pivotal LINZESS trials1

  • In Trial 5, LINZESS 72 mcg vs placebo, patients were 77% female and overall mean age was 46 years (range 18 to 90 years)1

Pretreatment symptoms and characteristics (Trials 3 and 4)1,3,10

Baseline frequency of CSBMs per week ranged from 0 to 2.91,3,10

Baseline frequency of SBMs per week ranged from 0 to 61,3,10

§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).1,9

Patients had significant improvement in CSBMs1

More than twice as many CSBM responders with LINZESS compared with those with placebo1

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%).

  • In Trials 3 and 4, CSBM frequency reached maximum level during Week 1 and was maintained over the remainder of the 12-week treatment period in both trials
  • During the 4-week RW period in Trial 3:
    • In LINZESS-treated patients re-randomized to placebo, CSBM and SBM frequency returned toward baseline within 1 week and did not result in worsening compared with 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 and SBM frequency similar to the levels observed in patients taking LINZESS during the treatment period

Patients had significant improvement in SBM and CSBM frequency over the treatment period1

LINZESS-treated patients averaged ~4.4 SBMs per week at Week 12, ~1.5 more than placebo1,3

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.

LINZESS increased CSBM frequency by ~2.3 CSBMs at Week 12, ~2 times more than than placebo1,3

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.

Patients had improved stool consistency over the treatment period1,3

LINZESS improved stool consistency more than placebo1,3

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.

  • Patients who received LINZESS across the 3 CIC trials had significantly greater improvements in stool consistency (as measured by the Bristol Stool Form Scale) compared with patients receiving placebo

Patients had a reduction in the amount of time pushing or physical effort to pass stool over the treatment period1,3

LINZESS showed greater improvements in straining compared with placebo1,3,10

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.

Next: Additional Trial Findings

Important Safety Information

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS

LINZESS is contraindicated in patients less than 6 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Use of LINZESS should be avoided in patients 6 years to less than 18 years of age. The safety and effectiveness of LINZESS have not been established in patients less than 18 years of age.

Contraindications
  • LINZESS is contraindicated in patients less than 6 years of age due to the risk of serious dehydration.
  • LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
Pediatric Risk
  • LINZESS is contraindicated in patients less than 6 years of age. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences.
  • Use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age.
Diarrhea
  • Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
  • In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
  • In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC clinical trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).

LINZESS® (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS‑C) and chronic idiopathic constipation (CIC).

If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about LINZESS, call Allergan Medical Information at 1.800.678.1605.

Please see below and full Prescribing Information for LINZESS.

Show
Important Safety Information

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS

LINZESS is contraindicated in patients less than 6 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Use of LINZESS should be avoided in patients 6 years to less than 18 years of age. The safety and effectiveness of LINZESS have not been established in patients less than 18 years of age.

Contraindications
  • LINZESS is contraindicated in patients less than 6 years of age due to the risk of serious dehydration.
  • LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
Pediatric Risk
  • LINZESS is contraindicated in patients less than 6 years of age. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences.
  • Use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 years to less than 18 years of age.
Diarrhea
  • Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
  • In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
  • In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC clinical trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).

LINZESS® (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS‑C) and chronic idiopathic constipation (CIC).

If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about LINZESS, call Allergan Medical Information at 1.800.678.1605.

Please see below and full Prescribing Information for LINZESS.