Trial Outcomes & Findings for Trial of Linaclotide in Patients With Chronic Idiopathic Constipation (NCT NCT02291679)

NCT ID: NCT02291679

Last Updated: 2017-06-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1223 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2017-06-15

Participant Flow

A total of 2244 participants were screened; 1223 were randomized and 1021 were not randomized (478 participants were screen failures and 543 participants were pretreatment failures).

Participant milestones

Measure	Placebo Matching placebo, once daily for 12 weeks	72 μg Linaclotide 72 μg oral linaclotide, once daily for 12 weeks	145 μg Linaclotide 145 μg oral linaclotide, once daily for 12 weeks
Overall Study STARTED	401	411	411
Overall Study COMPLETED	357	369	352
Overall Study NOT COMPLETED	44	42	59

Reasons for withdrawal

Measure	Placebo Matching placebo, once daily for 12 weeks	72 μg Linaclotide 72 μg oral linaclotide, once daily for 12 weeks	145 μg Linaclotide 145 μg oral linaclotide, once daily for 12 weeks
Overall Study Adverse Event	2	12	19
Overall Study Protocol Violation	5	1	7
Overall Study Withdrew Consent	18	10	15
Overall Study Lost to Follow-up	12	10	9
Overall Study Insufficient Therapeutic Response	5	5	7
Overall Study Other	2	4	2

Baseline Characteristics

Participants who did not have an SBM at baseline had missing Stool Consistency baseline scores.

Baseline characteristics by cohort

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks	145 μg Linaclotide n=411 Participants 145 μg oral linaclotide, once daily for 12 weeks	Total n=1223 Participants Total of all reporting groups
Age, Continuous	45.2 years STANDARD_DEVIATION 14.7 • n=401 Participants	45.8 years STANDARD_DEVIATION 14.3 • n=411 Participants	46.8 years STANDARD_DEVIATION 14.0 • n=411 Participants	46.0 years STANDARD_DEVIATION 14.3 • n=1223 Participants
Age, Customized 18 to < 40 years	142 Participants n=401 Participants	140 Participants n=411 Participants	128 Participants n=411 Participants	410 Participants n=1223 Participants
Age, Customized 40 to < 65 years	220 Participants n=401 Participants	235 Participants n=411 Participants	240 Participants n=411 Participants	695 Participants n=1223 Participants
Age, Customized ≥ 65 years	39 Participants n=401 Participants	36 Participants n=411 Participants	43 Participants n=411 Participants	118 Participants n=1223 Participants
Sex: Female, Male Female	316 Participants n=401 Participants	312 Participants n=411 Participants	314 Participants n=411 Participants	942 Participants n=1223 Participants
Sex: Female, Male Male	85 Participants n=401 Participants	99 Participants n=411 Participants	97 Participants n=411 Participants	281 Participants n=1223 Participants
Complete Spontaneous Bowel Movement Weekly Rate	0.25 CSBMs/week STANDARD_DEVIATION 0.48 • n=401 Participants	0.22 CSBMs/week STANDARD_DEVIATION 0.52 • n=411 Participants	0.20 CSBMs/week STANDARD_DEVIATION 0.44 • n=411 Participants	0.22 CSBMs/week STANDARD_DEVIATION 0.48 • n=1223 Participants
Spontaneous Bowel Movement Weekly Rate	1.56 SBMs/week STANDARD_DEVIATION 1.15 • n=401 Participants	1.74 SBMs/week STANDARD_DEVIATION 1.42 • n=411 Participants	1.67 SBMs/week STANDARD_DEVIATION 1.38 • n=411 Participants	1.66 SBMs/week STANDARD_DEVIATION 1.33 • n=1223 Participants
Stool Consistency Score	2.04 units on a scale STANDARD_DEVIATION 1.02 • n=359 Participants • Participants who did not have an SBM at baseline had missing Stool Consistency baseline scores.	1.94 units on a scale STANDARD_DEVIATION 0.93 • n=360 Participants • Participants who did not have an SBM at baseline had missing Stool Consistency baseline scores.	1.96 units on a scale STANDARD_DEVIATION 0.94 • n=364 Participants • Participants who did not have an SBM at baseline had missing Stool Consistency baseline scores.	1.98 units on a scale STANDARD_DEVIATION 0.96 • n=1083 Participants • Participants who did not have an SBM at baseline had missing Stool Consistency baseline scores.
Straining Score	3.51 units on a scale STANDARD_DEVIATION 0.88 • n=359 Participants • Participants who did not have an SBM at baseline had missing Straining baseline scores.	3.62 units on a scale STANDARD_DEVIATION 0.86 • n=360 Participants • Participants who did not have an SBM at baseline had missing Straining baseline scores.	3.52 units on a scale STANDARD_DEVIATION 0.82 • n=364 Participants • Participants who did not have an SBM at baseline had missing Straining baseline scores.	3.55 units on a scale STANDARD_DEVIATION 0.85 • n=1083 Participants • Participants who did not have an SBM at baseline had missing Straining baseline scores.
Abdominal Discomfort	4.76 units on a scale STANDARD_DEVIATION 2.56 • n=401 Participants	4.64 units on a scale STANDARD_DEVIATION 2.74 • n=411 Participants	4.71 units on a scale STANDARD_DEVIATION 2.66 • n=411 Participants	4.70 units on a scale STANDARD_DEVIATION 2.65 • n=1223 Participants
Abdominal Bloating	5.29 units on a scale STANDARD_DEVIATION 2.39 • n=401 Participants	5.24 units on a scale STANDARD_DEVIATION 2.61 • n=411 Participants	5.30 units on a scale STANDARD_DEVIATION 2.57 • n=411 Participants	5.27 units on a scale STANDARD_DEVIATION 2.52 • n=1223 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of 12-Week CSBM Overall Responders Responder	4.7 percentage of participants	13.4 percentage of participants
Percentage of 12-Week CSBM Overall Responders Non-Responder	95.3 percentage of participants	86.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week CSBM Frequency Rate	0.884 CSBMs/week Standard Error 0.142	1.725 CSBMs/week Standard Error 0.139

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week SBM Frequency Rate	1.329 SBMs/week Standard Error 0.169	2.366 SBMs/week Standard Error 0.166

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=344 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=349 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week Stool Consistency Score	1.065 units on a scale Standard Error 0.076	1.693 units on a scale Standard Error 0.074

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=344 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=349 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week Straining Score	-0.789 units on a scale Standard Error 0.051	-1.118 units on a scale Standard Error 0.050

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=226 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=244 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of 12-Week CSBM Overall Responders (>1 SBM/Week Subpopulation) Responder	7.1 percentage of participants	17.2 percentage of participants
Percentage of 12-Week CSBM Overall Responders (>1 SBM/Week Subpopulation) Non-Responder	92.9 percentage of participants	82.8 percentage of participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of Month 1 CSBM Responders Responder	6.2 percentage of participants	14.8 percentage of participants
Percentage of Month 1 CSBM Responders Non-Responder	93.8 percentage of participants	85.2 percentage of participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of Month 2 CSBM Responders Responder	9.5 percentage of participants	18.7 percentage of participants
Percentage of Month 2 CSBM Responders Non-Responder	90.5 percentage of participants	81.3 percentage of participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of Month 3 CSBM Responders Responder	14.2 percentage of participants	20.2 percentage of participants
Percentage of Month 3 CSBM Responders Non-Responder	85.8 percentage of participants	79.8 percentage of participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week Abdominal Bloating	-1.052 units on a scale Standard Error 0.097	-1.372 units on a scale Standard Error 0.095

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Change From Baseline in 12-Week Abdominal Discomfort	-1.146 units on a scale Standard Error 0.090	-1.323 units on a scale Standard Error 0.089

OTHER_PRE_SPECIFIED outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=401 Participants Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 Participants 72 μg oral linaclotide, once daily for 12 weeks
Percentage of 12-Week CSBM Overall Sustained Responders Responder	4.7 percentage of participants	12.4 percentage of participants
Percentage of 12-Week CSBM Overall Sustained Responders Non-Responder	95.3 percentage of participants	87.6 percentage of participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

72 μg Linaclotide

Serious events: 3 serious events

Other events: 79 other events

Deaths: 0 deaths

145 μg Linaclotide

Serious events: 2 serious events

Other events: 91 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=401 participants at risk Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 participants at risk 72 μg oral linaclotide, once daily for 12 weeks	145 μg Linaclotide n=411 participants at risk 145 μg oral linaclotide, once daily for 12 weeks
Gastrointestinal disorders Colitis	0.00% 0/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Respiratory, thoracic and mediastinal disorders Asthma	0.25% 1/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Renal and urinary disorders Azotaemia	0.00% 0/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Gastrointestinal disorders Constipation	0.25% 1/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.25% 1/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Vascular disorders Hypotension	0.00% 0/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.25% 1/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.
Gastrointestinal disorders Peptic ulcer	0.00% 0/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.24% 1/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	0.00% 0/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.

Other adverse events

Measure	Placebo n=401 participants at risk Matching placebo, once daily for 12 weeks	72 μg Linaclotide n=411 participants at risk 72 μg oral linaclotide, once daily for 12 weeks	145 μg Linaclotide n=411 participants at risk 145 μg oral linaclotide, once daily for 12 weeks
Gastrointestinal disorders Diarrhea	7.0% 28/401 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	19.2% 79/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.	22.1% 91/411 • From first dose of double-blind study drug up to Week 12/End of Treatment Visit (Day 85 + 3 days) for nonserious events and within 30 days of the date of last dose of double-blind study drug for serious events.

Additional Information

Michael Hall, MD

Ironwood Pharmaceuticals, Inc.

Phone: (617) 621-7722

Results disclosure agreements

• Principal investigator is a sponsor employee PI may publish or disclose the results of the study 24 months after final data lock provided that sponsor can review the publication prior to public release, sponsor can request removal of confidential information of sponsor (not including results of trial), and sponsor can request a publication delay in order to protect potentially patentable information. Furthermore, if a publication committee is developing an initial publication, PI is to delay disclosure until that publication is published.
• Publication restrictions are in place

Restriction type: OTHER