Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

A patient is considered to be a 6 out of 12 week APC responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

A patient is considered to be a 9 out of 12 week APC responder if, for at least 9 out of the first 12 weeks of the treatment period, the patient had at least 3 CSBMs, had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the Intent to Treat (ITT) Population. An observed-cases approach to missing postbaseline data was applied.

A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week. The Abdominal Pain score assesses patient's worst abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Abdominal discomfort was assessed on an 11-point scale where a value of 0 is none and a value of 10 is very severe.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Bloating was assessed on an 11-point scale where a value of 0 is none and a value of 10 is very severe.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Straining is measured on a 5-point scale where a value of 1 is not at all and a value of 5 is an extreme amount.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment; 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and included in the ITT Population; 134 patients with no pretreatment spontaneous bowel movements were excluded from the Straining analysis. An observed-cases approach to missing postbaseline data was applied.

The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7. 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\]).

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment; 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and included in the ITT Population; 134 patients with no pretreatment spontaneous bowel movements were excluded from the Stool Consistency analysis. An observed-cases approach to missing postbaseline data was applied.

The change from baseline in 12-week CSBM frequency (i.e., weekly CSBM frequency over the first 12 weeks of the Treatment Period).

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst. Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

The change from baseline in 12-week SBM frequency (i.e., weekly SBM frequency over the first 12 weeks of the Treatment Period).

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

A patient is considered to be an AP responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had a decrease of at least 30 percent in their Abdominal Pain score from baseline during a particular week.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.

Time frame: Change from Baseline to Week 12

Population: 805 patients were randomized to treatment. 804 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.