Trial of Linaclotide in Patients With Chronic Idiopathic Constipation

A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is 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: Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a primary endpoint; per protocol, data for the 145 μg dose arm were not collected for any pre-specified primary or secondary outcome measures.

Abdominal bloating was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal bloating score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal bloating scores reported during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

Abdominal discomfort was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal discomfort score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal discomfort scores reported during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A participant's 12-week CSBM Frequency Rate is the CSBM rate (CSBMs/week) calculated over the 12 weeks of the Treatment Period. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A participant's 12-week SBM Frequency Rate is the SBM rate (SBMs/week) calculated over the 12-weeks of the Treatment Period. An SBM is defined as a 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: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

Stool consistency was measured daily using the 7-point ordinal Bristol Stool Form Scale (BSFS; 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 \[entirely liquid\]). The participant's BSFS score for the Treatment Period is the average of the non-missing BSFS scores from the SBMs reported by the participant during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received ≥ 1 dose of study drug and reported an SBM during the Baseline period. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

Straining was measured daily using a 5-point ordinal scale (1 = not at all; 2 = a little bit; 3 = a moderate amount; 4 = a great deal; 5 = an extreme amount). The participant's straining score for the Treatment Period is the average of the non-missing straining scores from the SBMs reported by the participant during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Population: Intent-to-Treat Population: all randomized participants who received ≥ 1 dose of study drug and reported an SBM during the Baseline period. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Week 12

Population: Participants in the Intent-to-Treat Population who reported \>1 SBM/week during the Pretreatment Period (14 days prior to randomization). Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A Month 1 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 1 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 1

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A Month 2 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 2 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 2

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A Month 3 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 3 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 3

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.

A 12-week CSBM Overall Sustained Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period, including ≥ 3 of the last 4 weeks. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Week 12

Population: Intent-to-Treat Population: all randomized participants who received at least one dose of study drug. Only data for the 72 μg dose versus placebo arms were prospectively defined and evaluated as a secondary endpoint; data for the 145 μg dose arm were defined and evaluated as an additional endpoint per protocol.