Trial of Linaclotide in Patients With Irritable Bowel Syn... | NCT02559206

Name	Class
Forest Laboratories	INDUSTRY

Trial of Linaclotide in Patients With Irritable Bowel Syn... | NCT02559206 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
30 μg linaclotide DR1 and placebo	Experimental	Drug: Linaclotide
100 μg linaclotide DR1 and placebo	Experimental	Drug: Linaclotide
300 μg linaclotide DR1 and placebo	Experimental	Drug: Linaclotide
30 μg linaclotide DR2 and placebo	Experimental	Drug: Linaclotide
100 μg linaclotide DR2 and placebo	Experimental	Drug: Linaclotide
300 μg linaclotide DR2 and placebo	Experimental	Drug: Linaclotide
290 μg linaclotide IR and placebo	Experimental	Drug: Linaclotide
Placebo

Name	Type	Description	Arm Group Labels	Other Names
Linaclotide	Drug	Oral, once daily	100 μg linaclotide DR1 and placebo 100 μg linaclotide DR2 and placebo 290 μg linaclotide IR and placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo	Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.	Baseline, up to Week 12
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo	Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.	Baseline, up to Week 12
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo	A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.	Baseline, up to Week 12
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo	A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.	Baseline, up to Week 12
Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo	A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with <4 days of completed eDiary data for that week is not considered a responder for that week.

Contacts/Locations Module

Name	Affiliation	Role
Paul Chamberlin, MD	Ironwood Pharmaceuticals, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Ironwood Investigational Site		Huntsville	Alabama	35801	United States
Ironwood Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33065589	Derived	Chey WD, Sayuk GS, Bartolini W, Reasner DS, Fox SM, Bochenek W, Boinpally R, Shea E, Tripp K, Borgstein N. Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. Am J Gastroenterol. 2021 Feb 1;116(2):354-361. doi: 10.14309/ajg.0000000000000967.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Placebo: once daily (QD) for 12 weeks
FG001	Linaclotide IR 290 μg	Linaclotide immediate release (IR) formulation: 290 μg QD for 12 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Oct 4, 2016	Apr 8, 2020

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0014 subjects FG0021 subjects FG0035 subjects FG0043 subjects FG0050 subjects FG0061 subjects FG0070 subjects
Protocol Violation		FG0001 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004
Withdrawal by Subject		FG0003 subjects FG0013 subjects FG0021 subjects FG0033 subjects FG004
Lost to Follow-up		FG0003 subjects FG0015 subjects FG0023 subjects FG0033 subjects FG004
Lack of Efficacy		FG0001 subjects FG0010 subjects FG0023 subjects FG0032 subjects FG004
Other Not Specified		FG0000 subjects FG0010 subjects FG0020 subjects FG0031 subjects FG004

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo: once daily (QD) for 12 weeks
BG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
BG002	Linaclotide DR1 30 μg	Linaclotide DR1 30 μg QD for 12 weeks
BG003	Linaclotide DR1 100 μg	Linaclotide DR1 100 μg QD for 12 weeks
BG004	Linaclotide DR1 300 μg	Linaclotide DR1 300 μg QD for 12 weeks
BG005	Linaclotide DR2 30 μg	Linaclotide DR2 30 μg QD for 12 weeks
BG006	Linaclotide DR2 100 μg	Linaclotide DR2 100 μg QD for 12 weeks
BG007	Linaclotide DR2 300 μg	Linaclotide DR2 300 μg QD for 12 weeks
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00045.4± 14.7 BG00144.1± 14.4 BG00244.8± 14.9 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00053 BG00153 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00010 BG00114 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Caucasian

Title	Measurements
	BG00038 BG00143 BG002

Abdominal Pain

Based on 11-point numerical rating scale assessing symptom "at its worst in past 24 hours." 0=No symptom; 10=Worst possible.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0006.41± 1.85 BG0016.18

Complete Spontaneous Bowel Movement (CBSM) Weekly Rate

Mean

Standard Deviation

CBSM/week

Title

Denominators

Categories

Title	Measurements
	BG0000.29± 0.56 BG0010.34± 0.61 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR1 30 μg	Linaclotide DR1 30 μg QD for 12 weeks
OG003	Linaclotide DR1 100 μg	Linaclotide DR1 100 μg QD for 12 weeks
OG004	Linaclotide DR1 300 μg	Linaclotide DR1 300 μg QD for 12 weeks

Units	Counts
Participants	OG00066 OG00166 OG00267 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.370± 0.241 OG001-1.938± 0.241 OG002-1.667± 0.234 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		mixed model repeated measures (MMRM)		0.0839		LS Mean Difference (Lin-Placebo)	-0.569			2-Sided	95	-1.214	0.076					Superiority
OG000 OG002		MMRM		0.3661

Primary

Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR2 30 μg	Linaclotide DR2 30 μg QD for 12 weeks
OG003	Linaclotide DR2 100 μg	Linaclotide DR2 100 μg QD for 12 weeks

Primary

Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Least Squares Mean

Standard Error

CSBMs/week

Baseline, up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR1 30 μg	Linaclotide DR1 30 μg QD for 12 weeks
OG003	Linaclotide DR1 100 μg	Linaclotide DR1 100 μg QD for 12 weeks
OG004	Linaclotide DR1 300 μg

Primary

Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Least Squares Mean

Standard Error

CSBMs/week

Baseline, up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR2 30 μg	Linaclotide DR2 30 μg QD for 12 weeks
OG003	Linaclotide DR2 100 μg	Linaclotide DR2 100 μg QD for 12 weeks
OG004	Linaclotide DR2 300 μg

Primary

Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period.

Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder.
Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week.
Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week.

A participant with <4 days of completed eDiary data for that week is not considered a responder for that week.

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Count of Participants

Participants

up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR1 30 μg	Linaclotide DR1 30 μg QD for 12 weeks

Primary

Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period.

Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder.
Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week.
Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week.

A participant with <4 days of completed eDiary data for that week is not considered a responder for that week.

Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).

Posted

Count of Participants

Participants

up to Week 12

ID	Title	Description
OG000	Placebo	Placebo: QD for 12 weeks
OG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks
OG002	Linaclotide DR2 30 μg	Linaclotide DR2 30 μg QD for 12 weeks

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo: QD for 12 weeks	66	1	66	1	66
EG001	Linaclotide IR 290 μg	Linaclotide IR formulation: 290 μg QD for 12 weeks	66	1	66	10	66
EG002	Linaclotide DR1 30 μg	Linaclotide DR1 30 μg QD for 12 weeks	67	0	67	4	67
EG003	Linaclotide DR1 100 μg	Linaclotide DR1 100 μg QD for 12 weeks	67	0	67	9	67
EG004	Linaclotide DR1 300 μg	Linaclotide DR1 300 μg QD for 12 weeks	67	0	67	8	67
EG005	Linaclotide DR2 30 μg	Linaclotide DR2 30 μg QD for 12 weeks	67	0	67	0	67
EG006	Linaclotide DR2 100 μg	Linaclotide DR2 100 μg QD for 12 weeks	66	0	66	1	66
EG007	Linaclotide DR2 300 μg	Linaclotide DR2 300 μg QD for 12 weeks	66	0	66	2	66

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected66 at risk EG0020 affected67 at risk EG0030 affected67 at risk EG0040 affected67 at risk EG0050 affected67 at risk EG0060 affected66 at risk EG0070 affected66 at risk
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected66 at risk EG0020 affected67 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected66 at risk EG0020 affected67 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment		EG0001 affected66 at risk EG0019 affected66 at risk EG0022 affected67 at risk EG0035 affected67 at risk EG0047 affected67 at risk EG0050 affected67 at risk EG0061 affected66 at risk EG0072 affected66 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment		EG0000 affected66 at risk EG0011 affected66 at risk EG0022 affected67 at risk EG003

Group IDs	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	MMRM	0.0839		LS Mean Difference (Lin-Placebo)	-0.569	2-Sided	95	-1.214	0.076	Superiority
OG000 OG002	MMRM	0.1669		LS Mean Difference (Lin-Placebo)	-0.455	2-Sided	95	-1.102	0.191	Superiority
OG000 OG003	MMRM	0.3637		LS Mean Difference (Lin-Placebo)	-0.299	2-Sided	95	-0.947	0.348	Superiority
OG000 OG004	MMRM	0.4333		LS Mean Difference (Lin-Placebo)	-0.258	2-Sided	95	-0.905	0.389	Superiority
OG000 OG002 OG003 OG004	Trend Test	0.5528	Trend test performed using linear contrast statement for each DR formulation with placebo.							Superiority

Group IDs	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	MMRM	0.0110		LS Mean Difference (Lin-Placebo)	0.992	2-Sided	95	0.228	1.756	Superiority
OG000 OG002	MMRM	0.9013		LS Mean Difference (Lin-Placebo)	0.048	2-Sided	95	-0.716	0.812	Superiority
OG003	MMRM	0.4447		LS Mean Difference (Lin-Placebo)	0.299	2-Sided	95	-0.469	1.067	Superiority
OG000 OG004	MMRM	0.0904		LS Mean Difference (Lin-Placebo)	0.662	2-Sided	95	-0.104	1.428	Superiority
OG000 OG002 OG003 OG004	Trend Test	0.0700	Trend test performed using linear contrast statement for each DR formulation with placebo.							Superiority

Group IDs	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	MMRM	0.0110		LS Mean Difference (Lin-Placebo)	0.992	2-Sided	95	0.228	1.756	Superiority
OG000 OG002	MMRM	0.6801		LS Mean Difference (Lin-Placebo)	0.161	2-Sided	95	-0.604	0.925	Superiority
OG000 OG003	MMRM	0.8069		LS Mean Difference (Lin-Placebo)	-0.095	2-Sided	95	-0.861	0.670	Superiority
OG000 OG004	MMRM	0.5275		LS Mean Difference (Lin-Placebo)	-0.246	2-Sided	95	-1.011	0.519	Superiority
OG000 OG002 OG003 OG004	Trend Test	0.4201	Trend test performed using linear contrast statement for each DR formulation with placebo.							Superiority

Group IDs	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Cochran-Mantel-Haenszel	0.1663		Odds Ratio (OR)	1.71	2-Sided	95	0.79	3.70	Superiority
OG000 OG002	Cochran-Mantel-Haenszel	0.4399		Odds Ratio (OR)	1.39	2-Sided	95	0.61	3.17	Superiority
OG000 OG003	Cochran-Mantel-Haenszel	0.5540		Odds Ratio (OR)	1.27	2-Sided	95	0.57	2.85	Superiority
OG000 OG004	Cochran-Mantel-Haenszel	0.0262		Odds Ratio (OR)	2.39	2-Sided	95	1.10	5.19	Superiority
OG000 OG002 OG003 OG004	Correlation test	0.0249	For each DR formulation, the Correlation Test p-values are obtained from the correlation statistic controlling for geographic region.							Superiority

Group IDs	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Cochran-Mantel-Haenszel	0.1663		Odds Ratio (OR)	1.71	2-Sided	95	0.79	3.70	Superiority
OG000 OG002	Cochran-Mantel-Haenszel	0.7710		Odds Ratio (OR)	1.13	2-Sided	95	0.49	2.58	Superiority
OG000 OG003	Cochran-Mantel-Haenszel	0.8021		Odds Ratio (OR)	1.11	2-Sided	95	0.48	2.58	Superiority
OG000 OG004	Cochran-Mantel-Haenszel	0.8011		Odds Ratio (OR)	0.89	2-Sided	95	0.37	2.14	Superiority
OG000 OG002 OG003 OG004	Correlation test	0.8578	For each DR formulation, the Correlation Test p-values are obtained from the correlation statistic controlling for geographic region.							Superiority